Multiple variation of right renal and gonadal vascularization: report of two cases.

We present two cases of multiple anatomical variations of the renal and gonadal vessels. The first case presented duplication of the renal vein and the presence of an accessory renal artery. However, the most interesting fact, in this case, was that the right gonadal vein emptied into the inferior right renal vein instead of ending in the inferior vena cava as would typically be the case. In the second case, we also found an accessory renal artery and the right gonadal vein emptied at the exact junction between the right renal vein and the inferior vena cava. Clinicians and surgeons should be familiar with anatomical variations to provide an accurate diagnosis during preoperative studies and to avoid surprises in abdominal surgical procedures.

Este estudo apresenta dois casos de variação anatômica múltipla de vasos renais e gonadais. O primeiro caso apresentou uma duplicação da veia renal e a presença de uma artéria renal acessória. Porém, o fato mais interessante nesse caso foi a veia gonadal direita desembocar na veia renal direita inferior em vez de terminar na veia cava inferior, como seria o normal. No segundo caso, além de também encontrarmos uma artéria renal acessória, a veia gonadal direita desembocava no exato ponto de junção entre a veia renal direita e a veia cava inferior. Clínicos e cirurgiões devem estar familiarizados com a presença de possíveis variações dos vasos renais e gonadais, sendo um conhecimento imprescindível para obter um diagnóstico mais preciso e para evitar surpresas em procedimentos cirúrgicos abdominais.

The Fbn1 gene variant governs passive ascending aortic mechanics in the mgΔlpn mouse model of Marfan syndrome when superimposed to perlecan haploinsufficiency.

Introduction: Ascending thoracic aortic aneurysms arise from pathological tissue remodeling that leads to abnormal wall dilation and increases the risk of fatal dissection/rupture. Large variability in disease manifestations across family members who carry a causative genetic variant for thoracic aortic aneurysms suggests that genetic modifiers may exacerbate clinical outcomes. Decreased perlecan expression in the aorta of mgΔlpn mice with severe Marfan syndrome phenotype advocates for exploring perlecan-encoding Hspg2 as a candidate modifier gene. Methods: To determine the effect of concurrent Hspg2 and Fbn1 mutations on the progression of thoracic aortopathy, we characterized the microstructure and passive mechanical response of the ascending thoracic aorta in female mice of four genetic backgrounds: wild-type, heterozygous with a mutation in the Fbn1 gene (mgΔlpn), heterozygous with a mutation in the Hspg2 gene (Hspg2+/-), and double mutants carrying both the Fbn1 and Hspg2 variants (dMut). Results: Elastic fiber fragmentation and medial disarray progress from the internal elastic lamina outward as the ascending thoracic aorta dilates in mgΔlpn and dMut mice. Concurrent increase in total collagen content relative to elastin reduces energy storage capacity and cyclic distensibility of aortic tissues from mice that carry the Fbn1 variant. Inherent circumferential tissue stiffening strongly correlates with the severity of aortic dilatation in mgΔlpn and dMut mice. Perlecan haploinsufficiency superimposed to the mgΔlpn mutation curbs the viability of dMut mice, increases the occurrence of aortic enlargement, and reduces the axial stretch in aortic tissues. Discussion: Overall, our findings show that dMut mice are more vulnerable than mgΔlpn mice without an Hspg2 mutation, yet later endpoints and additional structural and functional readouts are needed to identify causative mechanisms.

Extracellular matrix and vascular dynamics in the kidney of a murine model for Marfan syndrome.

Fibrillin-1 is a pivotal structural component of the kidney's glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS.

"Split-Face" Evaluation of Collagen Changes Induced by Periorbital Fractional CO2 Laser Resurfacing.

BACKGROUND: Periorbital fractional CO2 laser resurfacing has been employed for facial rejuvenation purposes. However, to the best of our knowledge, no study has objectively assessed periorbital neoformation and remodeling of local cutaneous collagen, in a split-face model, from skin samples obtained during upper blepharoplasty. OBJECTIVES: The authors sought to objectively evaluate neoformation and remodeling of local cutaneous collagen after periorbital skin fractional CO2 laser resurfacing. METHODS: Sixteen female patients presenting with dermatochalasis and periorbital rhytids were evaluated in a prospective and comparative study. All patients underwent unilateral periorbital fractional CO2 laser resurfacing 30 days before upper blepharoplasty. Quantification of types I and III collagen from laser-treated and untreated eyelid skin samples obtained during upper blepharoplasty was assessed with histochemical analysis (Picrosirius Red staining). Laser resurfacing treatment was applied to the untreated side immediately after the upper blepharoplasty. Two blinded, independent physicians evaluated clinical improvement in pretreatment and 1- and 6-month posttreatment digital images. RESULTS: Histochemical analysis showed significantly higher intensity in collagen types I (treated: 158.7 ± 5.3, untreated: 139.2 ± 5.0; P < 0.0001) and III (treated: 105.1 ± 7.7, untreated: 104.1 ± 7.1; P < 0.0001) in the fractional CO2 laser treatment samples; a greater difference was detected in collagen type I. A significant improvement in periorbital rhytidosis was observed 1 month after laser resurfacing (23%); a greater improvement in the periorbital region was observed 6 months after laser resurfacing and upper blepharoplasty (43.67%). CONCLUSIONS: Periorbital fractional CO2 laser resurfacing was an effective method to improve palpebral skin, with histochemical evidence of increase in collagen types I and III.

Association of thoracic spine deformity and cardiovascular disease in a mouse model for Marfan syndrome.

AIMS: Cardiovascular manifestations are a major cause of mortality in Marfan syndrome (MFS). Animal models that mimic the syndrome and its clinical variability are instrumental for understanding the genesis and risk factors for cardiovascular disease in MFS. This study used morphological and ultrastructural analysis to the understanding of the development of cardiovascular phenotypes of the the mgΔloxPneo model for MFS. METHODS AND RESULTS: We studied 6-month-old female mice of the 129/Sv background, 6 wild type (WT) and 24 heterozygous animals from the mgΔloxPneo model. Descending thoracic aortic aneurysm and/or dissection (dTAAD) were identified in 75% of the MFS animals, defining two subgroups: MFS with (MFS+) and without (MFS-) dTAAD. Both subgroups showed increased fragmentation of elastic fibers, predominance of type I collagen surrounding the elastic fiber and fragmentation of interlaminar fibers when compared to WT. However, only MFS animals with spine tortuosity developed aortic aneurysm/dissection. The aorta of MFS+ animals were more tortuous compared to those of MFS- and WT mice, possibly causing perturbations of the luminal blood flow. This was evidenced by the detection of diminished aorta-blood flow in MFS+. Accordingly, only MFS+ animals presented a process of concentric cardiac hypertrophy and a significantly decreased ratio of left and right ventricle lumen area. CONCLUSIONS: We show that mgΔloxPneo model mimics the vascular disease observed in MFS patients. Furthermore, the study indicates role of thoracic spine deformity in the development of aorta diseases. We suggest that degradation of support structures of the aortic wall; deficiency in the sustenance of the thoracic vertebrae; and their compression over the adjacent aorta resulting in disturbed blood flow is a triad of factors involved in the genesis of dissection/aneurysm of thoracic aorta.

Accessing the biocompatibility of layered double hydroxide by intramuscular implantation: histological and microcirculation evaluation.

Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type-III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications.

PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3ß pathway.

We have identified previously a panel of markers (C1orf24, ITM1 and PVALB) that can help to discriminate benign from malignant thyroid lesions. C1orf24 and ITM1 are specifically helpful for detecting a wide range of thyroid carcinomas, and PVALB is particularly valuable for detecting the benign Hürthle cell adenoma. Although these markers may ultimately help patient care, the current understanding of their biological functions remains largely unknown. In this article, we investigated whether PVALB is critical for the acquisition of Hürthle cell features and explored the molecular mechanism underlying the phenotypic changes. Through ectopic expression of PVALB in thyroid carcinoma cell lines (FTC-133 and WRO), we demonstrated that PVALB sequesters free cytoplasmic Ca(2+), which ultimately lowers calcium levels and precludes endoplasmic reticulum (ER) Ca(2+) refilling. These results were accompanied by induced expression of PERK, an ER stress marker. Additionally, forced expression of PVALB reduces Ca(2+) inflow in the mitochondria, which can in turn cause changes in mitochondria morphology, increase mitochondria number and alter subcellular localization. These findings share striking similarity to those observed in Hürthle cell tumors. Moreover, PVALB inhibits cell growth and induces cell death, most likely through the AKT/GSK-3ß. Finally, PVALB expression coincides with Ca(2+) deposits in HCA tissues. Our data support the hypothesis that the loss of PVALB plays a role in the pathogenesis of thyroid tumors.