Loss Of Elastic Fibers Research Articles

Granulomatous Slack Skin with Hypercalcemia Indolently Mimicking Sarcoidosis

<p class="abstract">Granulomatous slack skin is a rare variant of cutaneous T-cell lymphoma characterized by lax skin and granulomatous infiltrate with loss of elastic fibers on histology. We report a unique case of a female presenting with CD30-granulomatous slack skin complicated by hypercalcemia, initially diagnosed, and managed as sarcoidosis. Interestingly, she had a history of previously treated CD30+ cutaneous T-cell lymphoma. Granulomatous slack skin can frequently mimic other benign and malignant cutaneous diseases, prompting the need for clinical vigilance from dermatologists.</p>

Expression of Estrogen Receptor Alpha and Evaluation of Histological Degeneration Scores in Fibroblasts of Hypertrophied Ligamentum Flavum: A Qualitative Study.

The most common spinal disorder in elderly is lumbar spinal stenosis (LSS), resulting partly from ligamentum flavum (LF) hypertrophy. Its pathophysiology is not completely understood. The present study wants to elucidate the role of estrogen receptor α (ER α) in fibroblasts of hypertrophied LF. LF samples of 38 patients with LSS were obtained during spinal decompression. Twelve LF samples from patients with disk herniation served as controls. Hematoxylin & Eosin (H&E) and Elastica stains and immunohistochemistry for ER α were performed. The proportions of fibrosis, loss and/or degeneration of elastic fibers and proliferation of collagen fibers were assessed according to the scores of Sairyo and Okuda. Group differences in the ER α and Sairyo and Okuda scores between patients and controls, male and female sex and absence and presence of additional orthopedic diagnoses were assessed with the Mann–Whitney U test. There was a tendency towards higher expression of ER α in LF fibroblasts in the hypertrophy group (p = 0.065). The Sairyo and Okuda scores were more severe for the hypertrophy group but, in general, not statistically relevant. There was no statistically relevant correlation between the expression of ER α and sex (p = 0.326). ER α expression was higher in patients with osteochondrosis but not statistically significant (p = 0.113). In patients with scoliosis, ER α expression was significantly lower (p = 0.044). LF hypertrophy may be accompanied by a higher expression of ER α in fibroblasts. No difference in ER α expression was observed regarding sex. Further studies are needed to clarify the biological and clinical significance of these findings.

Characterization of a Novel Model of Lumbar Ligamentum Flavum Hypertrophy in Bipedal Standing Mice.

ObjectiveTo explore the main causes of hypertrophied ligamentum flavum (HLF) and the possibility of using bipedal standing mouse model to simulate the pathological changes in human HLF.MethodsThirty‐two 8‐week‐old C57BL/6 male mice were randomly assigned to the experimental group (n = 16) and control group (n = 16). In the experimental group, mice were induced to adopt a bipedal standing posture by their hydrophobia. The experimental mice were maintained bipedal standing for 8 h a day with an interval of 2 h to consume food and water. The control mice were placed in a similar environment without bipedal standing. Eight 18‐month‐old C57BL/6 male mice were compared to evaluate the LF degeneration due to aging factor. Three‐dimensional (3D) reconstruction and finite element models were carried out to analyze the stress and strain distribution of the mouse LF in sprawling and bipedal standing postures. Hematoxylin and Eosin (HE), Verhoeff‐Van Gieson (VVG), and immunohistochemistry (IHC) staining were used to evaluate the LF degeneration of mice and humans. RT‐qPCR and immunofluorescence analysis were used to evaluate the expressions of fibrosis‐related factors and inflammatory cytokines of COL1A1, COL3A1, α‐SMA, MMP2, IL‐1β, and COX‐2.ResultsThe von Mises stress (8.85 × 10−2 MPa) and maximum principal strain (6.64 × 10−1) in LF were increased 4944 and 7703 times, respectively, in bipedal standing mice. HE staining showed that the mouse LF area was greater in the bipedal standing 10‐week‐old group ([10.01 ± 2.93] × 104 μm2) than that in the control group ([3.76 ± 1.87] × 104 μm2) and 18‐month‐old aged group ([6.09 ± 2.70] × 104 μm2). VVG staining showed that the HLF of mice (3.23 ± 0.58) and humans (2.23 ± 0.31) had a similar loss of elastic fibers and an increase in collagen fibers. The cell density was higher during the process of HLF in mice (39.63 ± 4.81) and humans (23.25 ± 2.05). IHC staining showed that the number of α‐SMA positive cells were significantly increased in HLF of mice (1.63 ± 0.74) and humans (3.50 ± 1.85). The expressions of inflammatory cytokines and fibrosis‐related factors of COL1A1, COL3A1, α‐SMA, MMP2, IL‐1β, and COX‐2 were consistently higher in bipedal standing group than the control group.ConclusionOur study suggests that 3D finite element models can help analyze the abnormal stress and strain distributions of LF in modeling mice. Mechanical stress is the main cause of hypertrophied ligamentum flavum compared to aging. The bipedal standing mice model can reflect the pathological characteristics of human HLF. The bipedal standing mice model can provide a standardized condition to elucidate the molecular mechanisms of mechanical stress‐induced HLF in vivo.

Deletion of type VIII collagen reduces blood pressure, increases carotid artery functional distensibility and promotes elastin deposition

Arterial stiffening is a significant predictor of cardiovascular disease development and mortality. In elastic arteries, stiffening refers to the loss and fragmentation of elastic fibers, with a progressive increase in collagen fibers. Type VIII collagen (Col-8) is highly expressed developmentally, and then once again dramatically upregulated in aged and diseased vessels characterized by arterial stiffening. Yet its biophysical impact on the vessel wall remains unknown. The purpose of this study was to test the hypothesis that Col-8 functions as a matrix scaffold to maintain vessel integrity during extracellular matrix (ECM) development. These changes are predicted to persist into the adult vasculature, and we have tested this in our investigation. Through our in vivo and in vitro studies, we have determined a novel interaction between Col-8 and elastin. Mice deficient in Col-8 (Col8−/−) had reduced baseline blood pressure and increased arterial compliance, indicating an enhanced Windkessel effect in conducting arteries. Differences in both the ECM composition and VSMC activity resulted in Col8−/− carotid arteries that displayed increased crosslinked elastin and functional distensibility, but enhanced catecholamine-induced VSMC contractility. In vitro studies revealed that the absence of Col-8 dramatically increased tropoelastin mRNA and elastic fiber deposition in the ECM, which was decreased with exogenous Col-8 treatment. These findings suggest a causative role for Col-8 in reducing mRNA levels of tropoelastin and the presence of elastic fibers in the matrix. Moreover, we also found that Col-8 and elastin have opposing effects on VSMC phenotype, the former promoting a synthetic phenotype, whereas the latter confers quiescence. These studies further our understanding of Col-8 function and open a promising new area of investigation related to elastin biology.

Accumulation of Plasma-Derived Lipids in the Lipid Core and Necrotic Core of Human Atheroma: Imaging Mass Spectrometry and Histopathological Analyses.

To clarify the pathogenesis of human atheroma, the origin of deposited lipids, the developmental mechanism of liponecrotic tissue, and the significance of the oxidation of phospholipids were investigated using mass spectrometry-aided imaging and immunohistochemistry.

28144 Cobblestoned skin on neck: The differential

Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-like PDE) is a benign cutaneous condition that mimics pseudoxanthoma elasticum (PXE). PXE is a hereditary distortion and calcification of elastic fibers, not only in cutaneous tissue, but in cardiac and ocular tissues. Histopathology is an important diagnostic tool to distinguish between the two and can save the patient from an extensive work-up if misdiagnosed as PXE. We present, herein, a 62-year-old healthy female of with an asymptomatic papular rash on her neck for 8 months. She wears a hijab, and reports frequent heat and sweat. The patient failed topical steroid creams given by her primary care provider. Exam showed multiple skin-colored to yellow smooth papules on the bilateral and posterior neck, and bilateral antecubital fossae. Biopsy from her left neck showed abrupt loss of elastic fibers in the papillary dermis with a Verhoeff-van Gieson stain. A von Kossa stain did not demonstrate calcium deposition, ruling out PXE. PXE-LPDE is likely an underdiagnosed acquired condition that occurs most commonly in women after the sixth decade of life and has overlapping clinical and histopathologic features with white fibrous papulosis, another benign condition that can be argued is the same entity. We favored PXE-LPDE in our patient due to the band-like loss of elastic fibers in the papillary dermis. Although chronic sun exposure has been implicated in its pathogenesis, our patient has been sun protected for most of her life. Unfortunately, no specific therapy has been shown to be successful in the treatment of PXE-like PDE.

Macrophage-biomimetic anti-inflammatory liposomes for homing and treating of aortic dissection

Aortic dissection (AD) is a life-threatening disease featured by the dissection of intimal layer and the formation of a blood-filled false lumen within the aortic wall. Recent studies revealed that the formation and progression of AD lesions is closely related to vascular inflammation and macrophage infiltration. However, the potential efficacy of anti-inflammatory therapy on the prevention and treatment of AD has not been extensively investigated. Herein, we proposed a biomimetic anti-inflammatory liposome (PM/TN-CCLP) co-loaded with curcumin and celecoxib (CC), modified with cell-penetrating TAT-NBD fusion peptide (TN), and further camouflaged by isolated macrophage plasma membrane (PM), as a potential nanotherapy for AD. In vitro results showed that PM/TN-CCLP exhibited low cytotoxicity and elevated cellular uptake by inflammatory macrophages, and prominently inhibited the transendothelial migration, inflammatory responses and ROS generation of macrophages. Moreover, the PM/TN-CCLP treatment significantly prevented the H2O2-induced smooth muscle cell apoptosis. In vivo experiments were performed on the acute and chronic AD mouse models, respectively. The results verified the elevated accumulation of PM-camouflaged liposome at the aorta lesions. Further, the anti-inflammatory liposomes, especially PM/TN-CCLP, could reduce the rupture rate of dissection, prevent the loss of elastic fibers, and reduce MMP-9 expression as well as macrophage infiltration in the aortic lesions. Notably, as compared with free drugs and TN-CCLP, the PM/TN-CCLP treatment displayed the longest survival period along with the minimal aortic injury on both acute and chronic AD mice. Taken together, the present study suggested that the macrophage-biomimetic anti-inflammatory nanotherapy would be a promising strategy for the prevention and therapy of aortic dissection.

Application of deep learning neural network in pathological image classification of non-inflammatory aortic membrane degeneration

Objective: To investigate the value of deep learning in classifying non-inflammatory aortic membrane degeneration. Methods: Eighty-nine cases of non-inflammatory aortic media degeneration diagnosed from January to June 2018 were collected at Beijing Anzhen Hospital, Capital Medical University, China and scanned into digital sections. 1 627 hematoxylin and eosin stained photomicrographs were extracted. Combined with the ResNet18-based deep convolution neural network model, 4-category classification of pathological images were performed to diagnose the non-inflammatory aortic lesion. Results: The prediction model of artificial intelligence assisted diagnosis had the best accuracy, sensitivity and precision in identifying lesions with smooth muscle cell nuclei loss, which were 99.39%, 98.36% and 98.36%, respectively. The classification accuracy of elastic fiber fragmentation and/or loss lesions was 98.08%, while that of intralamellar mucoid extracellular matrix accumulation lesions was 96.93%. The overall accuracy of the classification model was 96.32%, and the area under the curve was 0.982. Conclusions: The accuracy of deep learning neural network model in the 4-category classification of non-inflammatory aortic lesionsis confirmed based on digital photomicrographs. This method can effectively improve the diagnostic efficiency of pathologists.

Prospective Clinical Trial of the Latest Generation of Noninvasive Monopolar Radiofrequency for the Treatment of Facial and Upper Neck Skin Laxity.

Aging of the face and upper neck is a complex process characterized by loss of collagen and elastic fibers, resulting in clinical skin laxity. Noninvasive interventions such as monopolar capacitively coupled radiofrequency (MRF) have gained popularity, offering a safer and more convenient alternative to traditional surgical face lift. The latest MRF device features larger tips, vibration, cooling, and impedance matching. We performed the first open-label clinical trial, measuring the efficacy, safety, and patient satisfaction of this device for noninvasive lifting and tightening of the face and upper neck. Forty subjects 30 to 60 years of age with mild/moderate skin laxity of the face and upper neck were enrolled. After pretreatment with ketorolac 60 mg intramuscular injection, subjects underwent treatment with MRF. Follow-up evaluations were performed on Days 30, 60, and 180. Our study demonstrated that the newest generation MRF produced statistically significant improvement in skin laxity 6 months post-treatment, especially in the jowls and melolabial folds. According to the Investigator Global Aesthetic Improvement Score, 73% of subjects had improvement at 6 months post-treatment. Subject satisfaction and improvement questionnaires supported these findings. Our data coupled with the excellent adverse effect profile validates MRF as an attractive treatment modality for facial and upper neck skin laxity.

Therapeutic approach comparison in bicuspid aortic valve aortopathy and clinical practice implications.

Bicuspid aortic valve (BAV) is the most common heart valve malformation, and it may be associated with the development of long-term complications, such as aortic stenosis (AS) secondary to valvular calcification and aortic insufficiency (AI), with or without ascending aortic aneurysm (AAA). This study was performed at the Institute of Cardiovascular Diseases, Timişoara, Romania, from 2015 through 2018 and included a total of 105 patients with BAV. Out of the 105 BAV patients, 14 displayed AAA, alongside either AS or AI, and were selected undergo aortic valve replacement (AVR) alongside surgical replacement or aortoplasty of the ascending aorta, and the elastic fiber loss in the ascending aortic wall was evaluated for each patient. Two surgical interventions used alongside AVR in BAV patients with AAA and AS or AI were compared in this study: reduction ascending aortoplasty (RAA) and ascending aorta replacement (AAR). Postoperative follow-ups have shown RAA is useful short-term but that, in contrast to AAR, it leads to aortic redilatation over time. These results can contribute to a major future meta-analysis with the goal of improving the current clinical practice guidelines for BAV aortopathy.

Comparison of the damage to aorta wall in aortitis versus noninflammatory degenerative aortic diseases

BackgroundNot rarely aortitis is firstly identified in thoracic aorta aneurysm/dissection specimens only by histopathology in the absence of clinical evidence of systemic inflammatory disease emphasizing the importance of histology for the diagnosis of aortitis. Regardless of the improvement of the pathological assessment of aortic diseases by the recent consensus statements on surgical pathology of the aorta, histology can be confusing since medial degenerative changes (MDC) can be prominent in a background where inflammation is sometimes limited. This raises the question of the role of aging or other degenerative process versus the role of inflammation in the damage to aorta wall. Patients and MethodsIn this study, besides inflammation, we evaluated aorta samples from aortitis cases focusing on the histological scoring of MDC. In this retrospective single center study, we retrieved 719 cases of ascending aorta aneurysms or dissections operated on from January 2010 until June 2018. MDC (elastic fiber fragmentation and/or loss, smooth muscle nuclei loss, mucoid extracellular matrix accumulation intralemellar or translamellar) were estimated using a scoring system derived from that of the consensus statement. Noninfectious aortitis group versus age-matched non-inflammatory degenerative aortic disease group were compared. ResultsNoninfectious aortitis was pathologically diagnosed in 62 patients (8.6%). Among the 62 noninfectious aortitis patients, 47 patients (75.8%) had aortitis identified pathologically prior to the clinical diagnosis. Higher MDC scores were observed at all aortic sizes in aortitis group versus non-aortitis group, especially for elastic fiber damage and smooth muscle cell loss. ConclusionsAortitis is remarkably associated with severe damage to the aorta wall resulting in advanced MDC scores. Inflammatory process is responsible for higher MDC in the aorta wall than aging or other degenerative process.

Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.

Histopathological changes in dilated ascending aorta associated with aortic valve cuspidity.

Patients with a bicuspid aortic valve (BAV) often present with a dilated ascending aorta. However, the underlying pathogenesis for the observed changes in the aortic wall and the resulting aneurysmal dilation remains a subject of debate. This study aims to compare the histological abnormalities of the ascending aorta in BAV and tricuspid aortic valve (TAV) patients and their correlation with aortic diameter and patient age. A total of 376 patients from our institution's clinical database were included in the retrospective analysis. These patients underwent either elective surgery for ascending aorta dilation or emergency surgery for aortic dissection, either isolated or with a structurally diseased aortic valve. After excision, the ascending aorta samples were analysed by a pathologist. On histological examination, a higher degree of elastic fibre fragmentation and loss and mucoid extracellular matrix accumulation was present in the samples from TAV patients when compared with that from BAV patients (P < 0.001). However, correlation was poor for all variables when considering aortic diameter and histological abnormalities or age and histological abnormalities in both BAV and TAV patients. Our study demonstrates a greater incidence of severe histological abnormalities in TAV patients when compared with BAV patients.

Outside-in signaling by femoral cuff injury induces a distinct vascular lesion in adipose triglyceride lipase knockout mice.

Genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme for intracellular triglyceride (TG) hydrolysis, causes TG-deposit cardiomyovasculopathy (TGCV), a recently identified rare cardiovascular disorder (ORPHA code: 565612) in humans. One of the major characteristics of TGCV is a novel type of diffuse and concentric coronary atherosclerosis with ATGL-deficient smooth muscle cells (SMCs). Patients with TGCV have intractable coronary artery disease. Therefore, it is crucial to investigate the mechanisms underlying vascular lesions in ATGL deficiency using animal models. Cuff injury is an experimental procedure to induce vascular remodeling with neointimal formation with SMCs after placing a cuff around the adventitial side of the artery without direct influence on endothelium. We report the effect of cuff injury on femoral arteries of ATGL-knockout (ATGL⁻/⁻) mice. Cuff-induced concentric neointimal formation with migrating SMCs was exacerbated in ATGL⁻/⁻ mice, mimicking atherosclerotic lesions in patients with TGCV. In the media, cell death of SMCs and loss of elastic fibers increased. Perivascular infiltrating cells expressing tumor necrosis factor-α (TNF-α) were more prominent in ATGL⁻/⁻ mice than in wild-type (WT) mice. In Boyden chamber experiments, a greater number of ATGL⁻/⁻ SMCs migrated in response to TNF-α compared to WT SMCs. These data, for the first time, demonstrated that outside-in signaling by cuff-induced neointimal formation where paracrine stimuli from adventitial infiltrating cells may lead to neointimal formation and mediolysis in ATGL-deficient conditions. Cuff injury might be a valuable model for understanding the mechanisms underlying the development of atherosclerotic lesions in patients with TGCV.

The role of matrix metalloproteinase-2 on age-dependent arterial stiffness

Abstract Introduction Arterial stiffness is a well-characterized sign of vascular aging. It strongly predicts the development of several cardiovascular diseases (CVD), such as hypertension, stroke and heart failure. The age-dependent stiffening of elastic arteries is primarily attributed to the loss of interlaminar elastic fibers and the increase of collagen fibers. This process is regulated by matrix metalloproteinases (MMPs), including MMP-2. A strong correlation between MMP-2 levels and arterial stiffness has been previously described. However, the causative link between age-dependent arterial stiffness and MMP-2 remains unclear. Purpose In this study, we aimed to prospectively investigate the effect of MMP-2 gene silencing on the development of age-dependent carotid stiffness in wild type (WT) mice. Methods Pulse Wave Velocity (PWV), as the gold standard technique to assess arterial stiffness, was assessed in the right common carotid artery (RCCA) of C57BL/6 WT mice of various ages ranging between 3 and 25 months. Plasma and vascular levels of MMP-2 on RCCA were also measured and correlate with PWV. Moreover, aged WT male mice (18–21-month-old) were treated for 4 weeks with either MMP-2 siRNA or Scr siRNA via tail vein injection every 4 days and PWV was assessed at baseline, 2 and 4 weeks. Results Mouse carotid PWV increased and was positively correlated with age in our in vivo longitudinal study. Increases of vascular and circulating MMP-2 levels were also observed in this study. MMP-2 knockdown by siRNA treatment reduced vascular MMP-2 level (Fig. 1), which in turn attenuated age-dependent carotid stiffening (data not shown). siMMP-2 treated animals also showed an increase of elastin to collagen ratio. Furthermore, enhanced phosphorylation of the activatory eNOS Ser1177 was observed in the siMMP-2 group without affecting the level of total eNOS and Akt phosphorylation. Interestingly, co-immunoprecipitation experiments demonstrated that MMP-2 directly interacts with eNOS and this interaction is augmented with age. Conclusion The silencing of MMP-2 attenuates age-dependent carotid stiffness by affecting elastin to collagen ratio and interfering with eNOS activation. Thus, MMP-2 may mediate ECM remodeling and endothelial-dependent vasorelaxation in the development of age-dependent vascular stiffness. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation, Foundation for Cardiovascular Research-Zurich Heart House

Morphological Changes in the Ligamentum Flavum in Degenerative Lumbar Canal Stenosis: A Prospective, Comparative Study.

Study DesignProspective, comparative.PurposeTo compare the histopathological and electron microscopic changes in the ligamentum flavum (LF) between degenerative lumbar canal stenosis (LCS) and lumbar disk herniation (LDH).Overview of LiteratureThe LF has been implicated as a key structure in the pathogenesis of LCS. With aging, the LF undergoes morphological changes–a decrease in the elastic component and an increase in the collagen component, in addition to other focal changes. By comparing the histopathological and electron microscopic picture of the LF in elderly patients with LCS with that in young patients with LDH, the role of this ligament in the pathogenesis of LCS may be clarified.MethodsForty patients were prospectively recruited and divided into two groups: group 1 included 20 patients with degenerative LCS aged >55 years and group 2 included patients with LDH aged <35 years. The ligament flava were collected during the patients’ surgery. The features noted on histopathological examination included the fibrosis score, the loss of elastic fibers, calcification, chondroid metaplasia, mucinous degeneration, vascularization, long septa, clefts, granulation tissue, and ganglion-like cysts. The features noted on electron microscopic examination included the elastic fiber thickness, the quality of elastic fibers, the elastic:collagen ratio, calcification, melanin fibers, remnants of necrotic cells, and electron-dense material in the LF. All parameters were compared between group 1 and group 2.ResultsOn histopathological examination, the two groups exhibited significant differences regarding three parameters: chondroid metaplasia, long septa, and ganglion-like cysts. On electron microscopy examination, significant differences were observed between the two groups regarding two parameters: the quality of elastic fibers and the elastic:collagen ratio.ConclusionsCharacteristic morphological changes may be noted on histopathological and electron microscopic examination that mark the degenerative changes in the LF that contribute to the occurrence and pathogenesis of degenerative LCS.

Extensive Primary Anetoderma Refractory to Erbium YAG Fractionally Ablative Laser

Primary anetoderma is a rare elastolytic disorder characterized by well-circumscribed flaccid, atrophic macules and patches caused by focal loss of elastic fibers. Anetoderma is divided into two forms: primary, which is idiopathic and occurs on clinically normal skin, and secondary, which follows a prior dermatosis. Although it is indolent, the lesions of anetoderma persist and may be associated with significant aesthetic changes causing potential psychosocial difficulties. Anetoderma has been successfully treated with ablative, pulsed dye and non-ablative fractionated lasers. Patients with secondary anetoderma and anetoderma limited to a relatively small body surface area may be more amenable to laser treatment than patients with extensive involvement.

Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model

Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury.

Histologic Abnormalities of the Ascending Aorta: Effects on Aortic Remodeling after Intracardiac Repair of Tetralogy of Fallot.

We evaluated aortic tissue specimens from patients undergoing tetralogy of Fallot repair, to determine whether histologic abnormalities affect postsurgical aortic remodeling and other patient-related variables. Using light microscopy, we studied full-thickness aortic wall tissue operatively excised from 118 consecutive patients undergoing intracardiac repair of tetralogy of Fallot. We performed multiple linear regression analysis to identify independent predictors of change in aortic root dimensions, which we measured with echocardiography after repair and every 3 months thereafter. Thirty histologically normal specimens were used as controls. Elastic fiber fragmentation was found in 74.6% of the abnormal specimens, mucoid extracellular matrix accumulation in 49.2%, smooth muscle cell nuclei loss in 39%, smooth muscle cell disorganization in 28.8%, and medial fibrosis in 52.5%. At a mean follow-up time of 83.55 ± 42.08 months, mean aortic sinotubular diameter decreased from 28.79 ± 9.15 to 27.16 ± 8.52 mm/m2 (r=-0.43; P<0.001). Aortic sinotubular diameter decreased by 0.6 mm/m2 among females (β=0.6, SE=0.31; P=0.05) and by 0.88 mm/m2 in patients who had elastic fiber fragmentation or loss (β=0.88, SE=0.38; P=0.02). In bivariate and multiple linear regression analysis, duration of follow-up emerged as an independent predictor of aortic remodeling. The aortic histopathologic changes in our patients had an independent negative impact on the degree of aortic remodeling after surgery. We observed the most improved aortic sinotubular diameter in patients who had either histologically normal aortas or aortas with elastic fragmentation.

1. Azygous vein aneurysm presenting as a mediastinal mass: A case report

Background: Azygous vein aneurysm is a rare occurrence and presenting as a mediastinal mass is even rarer. Its complications are dreadful as it may lead to rupture and demise if not properly diagnosed and attended. Aims: This report is prepared to present an infrequent ailment, clinical presentation, histopathologic findings and course of the disease. Results: This patient, a 58-year-old female, presented with dyspnoea and chest pain. She was brought to a hospital and showed tachypnoea. Upon admission, chest radiograph was performed displaying a lobulated soft tissue mass in the right suprahilar region which at first was considered as soft tissue mass versus an enlarged lymph node. The patient was transferred to the Philippine Heart Center for definitive management. Computed tomography (CT) of the chest showed a large saccular aneurysm (7.8×7.4×7.7 cm) emanating from the right lateral wall of the superior vena cava (SVC) with thrombus formation within its lumen, extending to the distal SVC. The patient was scheduled for aneurysm repair. Intraoperatively, the SVC was identified and discovered that the aneurysmally dilated vein was the azygous vein instead of the SVC. It was resected and the operation was successful. The specimen consisted of several, tan-gray, rubbery to friable tissues aggregately measuring 6.5×5.5×2.0 cm. Microsections showed vessel wall with fibrosis, myxoid areas within the medial layer and congested vascular channels in the adventitia. Haemorrhage and thrombus were seen. Trichrome stain revealed areas of fibrosis and marked increase in collagen fibres. Elastic stain revealed elastic fibre loss and fragmentation. The final histologic diagnosis was aneurysmal vessel wall with myxoid degeneration of media. Conclusion: Azygous vein aneurysm is rare, probably the first ever reported entity in the Philippines. Proper approach in early detection and keen clinical judgement are necessary to ensure good patient outcomes.