Stereological analysis of elastic fibers of the corpus cavernosum of rats during the aging process

Abstract Purpose To evaluate changes in the quantity of elastic fibers in the corpora cavernosa of rats during the natural aging process, and to assess the degree of this change by determining volumetric density (Vv) at different ages via stereological analysis. Methods Forty-eight rats, raised under similar conditions, were subjected to the natural aging process and divided into four groups (G1 to G4), according to age at the time of penectomy (6, 9, 12, and 24 months, respectively). Histological sections of the middle segment of the penis were stained with Weigert's resorcin-fuchsin, and the volumetric density (Vv) of elastic fibers of the corpora cavernosa were determined via stereological analysis. Results There were no statistically significant differences in Vv among groups G1, G2, and G3. These three groups were therefore considered as a single group. The mean Vv of this group showed a statistically significant reduction compared to that of G4 (0.16 vs. 0.11, p<0.05). Conclusion Natural aging in rats was responsible for a reduction in volumetric density of elastic fibers of the corpora cavernosa (approximately 30% decrease in Vv) during senescence.

Epithelial-mesenchymal interaction mechanisms leading to the over-expression of neprilysin are involved in the UVB-induced formation of wrinkles in the skin.

In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Repetitive UVB irradiation of animal skin at suberythemal doses significantly reduces its elastic properties, resulting in the formation of wrinkles. That also elicits a marked alteration in the three-dimensional structure of elastic fibres, which is closely associated with a subsequent reduction in the elastic properties of the skin. While UVB irradiation stimulates the activity of skin fibroblast-derived elastase in the dermis, a synthetic inhibitor specific for skin fibroblast-derived elastase as well as an extract of Zingiber officinale (L.) Rose capable of inhibiting skin fibroblast-derived elastase, but not neutrophil elastase, prevented wrinkle formation in our studies of animal and human facial skin, respectively. The close interrelationship among wrinkle formation, elastic properties and elastic fibre linearity is revealed by the effects of different concentrations of the elastase inhibitor, which indicates that enhanced elastase activity by dermal fibroblasts plays a pivotal role in the UVB wrinkling mechanism. Fortunately, we were able to identify human skin fibroblast-derived elastase as the previously known enzyme neprilysin/neutral endopeptidase. Using both a UVB-conditioned medium assay and a co-culture system, we characterized the epithelial-mesenchymal interaction between keratinocytes and fibroblasts which leads to increased expression of neprilysin at the transcriptional, translational and enzymatic levels. Our results demonstrate that interleukin-1α and granulocyte-macrophage colony-stimulating factor are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate the expression of neprilysin by skin fibroblasts.

Cricothyroid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial and Capsular Tissues.

OBJECTIVE: The present study aimed to clarify individual variations in the cricothyroid joint (CT joint). METHODS: Using 30 specimens of the CT joint obtained from elderly donated cadavers, we examined the composite fibers of the capsular ligament as well as the morphology of the synovial tissue. RESULTS: The capsular ligament consistently contained abundant thick elastic fiber bundles on the anterior side of the joint (anterior band) and an elastic fiber-made mesh on the posterior side (posterior mesh). The synovial membrane, lined by synovial macrophages, was usually restricted to the recesses in the medial or inferior end of the joint cavity. Without the synovial lining, elastic fibers of the capsular ligament were subsequently detached, dispersed, and exposed to the joint cavity. We also observed a folded and thickened synovial membrane and a hypertrophic protrusion of the capsular ligament. In six specimens, the joint cavity was obliterated by debris of synovial folds and elastic fiber-rich tissues continuous with the usual capsular ligament. Notably, with the exception of two specimens, we did not find lymphocyte infiltration in the degenerative synovial tissue. DISCUSSION: We considered the CT joint degeneration to be a specific, silent form of osteoarthritis from the absence of lymphocyte infiltration. For high-pitched phonation, the elderly CT joint seemed to maintain its anterior gliding and rotation with the aid of elastic fiber-rich tissues compensating for the loss of congruity between the joint cartilage surfaces. Conversely, however, high-pitched phonation may accelerate obliteration of the joint.

Estrogen attenuates TGF-ß1 induced elastogenesis in rat urethral smooth muscle cells by inhibiting Smad response elements.

PURPOSE: We investigated the effect and mechanism of estrogen on elastogenesis in urethral smooth muscle cells in vitro. MATERIALS AND METHODS: Urethral smooth muscle cells were isolated from normal adult female rats. For elastogenesis assay cells were treated with TGF-ß1, the potent TGF-ß1 receptor inhibitor SB431542 and estrogen for 2 weeks. Real-time polymerase chain reaction was performed to assay gene expression during this process. Activity of the TGF-ß1 responsive elements CAGA(12)-Luc and GCCG(12)-Luc were also assayed. Estrogen receptor and Smad2/3 interaction was evaluated by immunoprecipitation and Western blot. RESULTS: TGF-ß1 induced elastogenesis in rat urethral smooth muscle cells. This effect was partially blocked by estrogen and completely abrogated by SB431542. SB431542 completely inhibited activation of the Smad2/3 response element CAGA(12)-Luc and estrogen significantly inhibited activation. The Smad1/4 response element GCCG(12)-Luc was not affected by SB431542 treatment but estrogen partially inhibited the activation of GCCG(12)-Luc induced by TGF-ß1. Estrogen receptor bound to Smad 2 and 3 in vitro. CONCLUSIONS: Estrogen attenuated TGF-ß1 induced elastogenesis via binding of its activated receptor to Smad2/3 to inhibit the TGF-ß1 response element in rat urethral smooth muscle cells.

Elastic nature of the lacrimal canalicular wall.

PURPOSE: To examine the elastic nature of the lacrimal canalicular wall. METHODS: Fifteen postmortem specimens of 11 Japanese individuals (8 right, 7 left; age range, 45-89 years at death) fixed in 10% buffered formalin were axially sliced parallel to the lower eyelid margin to include all 3 portions of the lacrimal canaliculi (intrasac, extrasac-extramuscular, and intramuscular portions). All specimens were stained with Elastica van Gieson. Microscopic photographs were taken and converted to white (elastic fibers) and black (the other tissues) images to measure the elastic fibers in an area in each portion. RESULTS: Six specimens in 4 individuals (2 right, 4 left; age range, 62-87 years) included all 3 portions. The area of elastic fibers in the intrasac portion (mean area, 125.8±93.6 white dot) was not significantly different from that in the extrasac-extramuscular portion (p=0.637: mean area, 268.5±150.2 white dots) but was significantly smaller than the areas in the intramuscular portion (p<0.001: mean area, 796.3±278.1 white dots) and Horner's muscle fascia (p<0.001: mean area, 1052.8±250.1 white dots). The area of elastic fibers in the extrasac-extramuscular portion was also significantly smaller than areas in the intramuscular portion (p=0.001) and Horner's muscle fascia (p<0.001). There was no significant difference in the area between the intramuscular portion and Horner's muscle fascia (p=0.172). CONCLUSIONS: The elastic nature of the lacrimal canalicular wall was different in areas with or without Horner's muscle envelope.

Corneal resistance factor and corneal hysteresis in a 6- to 18-year-old population.

PURPOSE: To determine the distribution and normal range of the corneal resistance factor (CRF) and corneal hysteresis (CH) in the 6- to 18-year age range and their relationship with biometric components. SETTING: Dezful, Iran. DESIGN: Cross-sectional study. METHODS: This study of Dezful school children used a multistage, stratified, cluster approach sampling. All students had examinations for biometry, noncycloplegic refraction, and corneal biomechanical properties; the examinations were performed in the same order in all cases. RESULTS: Of the 864 selected students, 683 participated in the study. The mean CRF and CH was 11.74 mm Hg±1.77 (SD) (95% confidence interval [CI], 11.58-11.89) and 11.49±1.91 mm Hg (95% CI, 11.33-11.65), respectively. In a linear multiple regression model, the CRF significantly correlated with female sex (ß coefficient=0.488, P=.013), central corneal thickness (CCT) (ß coefficient=.034, P=.001), and keratometry (ß-coefficient=0.157, P=.003) and CH significantly correlated with CCT (ß coefficient=0.025, P<.001), axial length (ß coefficient=-0.303, P=.011), and keratometry (ß coefficient=0.11, P=.043). Each year increase in age was associated with a 42-unit decrease in the peak 1 area (P=.003). CONCLUSIONS: The distribution of CRF and CH in an Iranian population was symmetrical and bell shaped. However, the CRF did not have a normal distribution. The mean CRF and CH were higher than those reported in almost all previous studies. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Transrectal real-time tissue elastography - an effective way to distinguish benign and malignant prostate tumors.

BACKGROUND: To investigate the relationship between extracellular matrix parameters and texture of prostatic lesions evaluated by transrectal real-time tissue elastography (TRTE). METHODS: 120 patients suspicious for prostate cancer underwent TRTE. Targeted biopsies were carried out after 12-core systematic biopsy. Epithelia were stained with hematoxylin-eosin, and Victoria blue and Ponceau S were used to stain elastic-collagen fibers, and picric acid-sirius red for visualization of collagen type I (Col1) and III (Col3). Smooth muscles were visualized by immunohistochemistry. All image analyses were performed in a blind manner using Image Pro Plus 6.0, and the area ratios of epithelium, elastic fibers, collagen fibers and Col1/Col3 were determined. RESULTS: 42 patients with typical elastograms were included in the final data analysis. Significant differences were detected between the benign and malignant groups in the area ratios of epithelium (P = 0.01), smooth muscles and Col1/Col3 (P = 0.04, P = 0.02, respectively). There were no significant differences in the area ratios of epithelium, smooth muscle and elastic fibers between the stiff and soft lesion groups. The area ratio of Col1 was (0.05 ± 0.03) in the stiff group, and (0.02 ± 0.01) in the soft group (P= 0.00). However, the area ratio of Col3 was (0.03 ± 0.02) in the stiff group, and (0.05 ± 0.04) in the soft group (P = 0.16). Col1/Col3 in the stiff group (1.99 ± 1.59) was greater than in the soft group (0.71 ± 0.64) (P = 0.01). CONCLUSIONS: Tissue hardness of prostatic tumors was mainly dependent on the Col1 content, Col1/Col3 being higher in malignant than in benign lesions, so the prostate tissue texture can be used as a target for distinguishing between the two with TRTE.

Elastophagocytosis: underlying mechanisms and associated cutaneous entities.

Elastophagocytosis is the phagocytosis of elastic fibers that can microscopically be seen in the cytoplasm of histiocytes, multinucleated giant cells, or both. Generally believed to be a characteristic feature of certain granulomatous disorders such as annular elastolytic giant cell granuloma or elastolytic disorders such as mid-dermal elastolysis, this feature has also been described in other cutaneous inflammatory conditions, cutaneous malignancies, infectious entities, and secondary to certain medications. The list of diseases that can exhibit this peculiar finding on histopathology is long. In this review we attempt to shed light on the available literature concerning the pathogenesis of this phenomenon and the plethora of skin conditions that exhibit elastophagocytosis.

Prostaglandin E2 inhibits elastogenesis in the ductus arteriosus via EP4 signaling.

BACKGROUND: Elastic fiber formation begins in mid-gestation and increases dramatically during the last trimester in the great arteries, providing elasticity and thus preventing vascular wall structure collapse. However, the ductus arteriosus (DA), a fetal bypass artery between the aorta and pulmonary artery, exhibits lower levels of elastic fiber formation, which promotes vascular collapse and subsequent closure of the DA after birth. The molecular mechanisms for this inhibited elastogenesis in the DA, which is necessary for the establishment of adult circulation, remain largely unknown. METHODS AND RESULTS: Stimulation of the prostaglandin E2 (PGE2) receptor EP4 significantly inhibited elastogenesis and decreased lysyl oxidase (LOX) protein, which catalyzes elastin cross-links in DA smooth muscle cells (SMCs), but not in aortic SMCs. Aortic SMCs expressed much less EP4 than DASMCs. Adenovirus-mediated overexpression of LOX restored the EP4-mediated inhibition of elastogenesis in DASMCs. In EP4-knockout mice, electron microscopic examination showed that the DA acquired an elastic phenotype that was similar to the neighboring aorta. More importantly, human DA and aorta tissues from 7 patients showed a negative correlation between elastic fiber formation and EP4 expression, as well as between EP4 and LOX expression. The PGE2-EP4-c-Src-phospholipase C (PLC)γ-signaling pathway most likely promoted the lysosomal degradation of LOX. CONCLUSIONS: Our data suggest that PGE2 signaling inhibits elastogenesis in the DA, but not in the aorta, through degrading LOX protein. Elastogenesis is spatially regulated by PGE2-EP4 signaling in the DA.

Ocular rigidity, outflow facility, ocular pulse amplitude, and pulsatile ocular blood flow in open-angle glaucoma: a manometric study.

PURPOSE: To compare ocular rigidity (OR) and outflow facility (C) coefficients in medically treated open-angle glaucoma (OAG) patients and controls, and to investigate differences in ocular pulse amplitude (OPA) and pulsatile ocular blood flow (POBF) between the two groups. METHODS: Twenty-one OAG patients and 21 controls undergoing cataract surgery were enrolled. Patients with early or moderate primary or pseudoexfoliative OAG participated in the glaucoma group. A computer-controlled system, consisting of a pressure transducer and a microstepping device was employed intraoperatively. After cannulation of the anterior chamber, IOP was increased by infusing the eye with microvolumes of saline solution. IOP was recorded after each infusion step. At an IOP of 40 mm Hg, an IOP decay curve was recorded for 4 minutes. OR coefficients, C, OPA, and POBF were estimated from IOP and volume recordings. RESULTS: There were no differences in age or axial length in the two groups. The OR coefficient was 0.0220 ± 0.0053 µl(-1) in the OAG and 0.0222 ± 0.0039 µl(-1) in the control group (P = 0.868). C was 0.092 ± 0.082 µL/min/mm Hg in the glaucoma group compared with 0.149 ± 0.085 µL/min/mm Hg in the control group at an IOP of 35 mm Hg (P < 0.001) and 0.178 ± 0.133 µL/min/mm Hg vs. 0.292 ± 0.166 µL/min/mm Hg, respectively, at an IOP of 25 mm Hg (P < 0.001). There were no differences in OPA or POBF between the two groups in baseline and increased levels of IOP (P > 0.05). CONCLUSIONS: Manometric data reveal lower C in OAG patients and increased C with increasing IOP. There were no differences in the OR coefficient, OPA, and POBF between medically treated OAG patients and controls, failing to provide evidence of altered scleral distensibility and choroidal blood flow in OAG.

Influência do envelhecimento na qualidade da pele de mulheres brancas: o papel do colágeno, da densidade de material elástico e da vascularização / Influence of aging on the skin quality of white-skinned women: the role of collagen, elastic material density, and vascularization

INTRODUÇÃO: O objetivo deste estudo é avaliar a influência do envelhecimento na qualidade da pele de mulheres brancas, analisando o colágeno, as fibras elásticas e a vascularização. MÉTODO: Foi realizada análise histológica e morfométrica de 218 retalhos pré-auriculares de mulheres brancas, que se submeteram a cirurgia estética facial. Foram utilizados o imunomarcador AntiCD 34, que evidencia os vasos sanguíneos, a coloração de Weigert, para visibilização das fibras elásticas, e a coloração de Picrosirius Ultrared, para analisar e quantificar os colágenos I, III e total. Os dados foram analisados de acordo com a faixa etárias das doadoras: < 40 anos, 40 anos a 49 anos, 50 anos a 59 anos, 60 anos a 69 anos, e > 70 anos. RESULTADOS: Foi observada fragmentação e desorganização das fibras de colágeno, especialmente acima de 60 anos. Não houve diferenças significantes entre a idade e a espessura da derme e da epiderme, porém foi identificada relação com as porcentagens de colágeno I, III e total (P < 0,001). Houve aumento da densidade de fibras elásticas com a progressão da idade (P < 0,001). Comparando-se as peles das pacientes de faixas etárias vizinhas, com diferença de uma década entre elas, não houve diferença significativa na quantidade de material elástico dessas peles; porém, ao se comparar aquelas com diferença de 2 ou mais décadas nas faixas etárias, o aumento foi significante (P < 0,05). A diferença do número de vasos não foi significante (P = 0,112). CONCLUSÕES: O envelhecimento promoveu redução do colágeno, degradação e fragmentação das fibras, e aumento da densidade de material elástico desorganizado, e não influenciou no número de vasos sanguíneos da derme.

BACKGROUND: In the present study, we aimed to evaluate the influence of aging on the skin quality of white-skinned women by assessing collagen levels, elastic material density, and vascularization. METHODS: Histological and morphometric analyses were performed on 218 preauricular skin fragments from white-skinned women who underwent facial cosmetic surgery. Anti-CD34 was used to identify the blood vessels, Weigert's staining was used to visualize elastic fibers, and Picro-sirius Ultra Red staining was employed for analyzing and quantifying the expression of type I, III, and total collagen. Data were analyzed according to the following donor age groups: < 40, 40-49, 50-59, 60-69, and > 70 years. RESULTS: Fragmentation and disorganization of collagen fibers were observed in certain samples, particularly in samples from patients aged > 60 years. Significant differences between age and the thickness of the dermis and epidermis were not detected. However, a relationship was identified between age and the percentages of type I, III, and total collagen, and an increase of elastic fibers density was associated with age progression (P < 0.001). The comparison of the skin of patients with a decade difference in age did not reveal a significant difference in the elastic material quality; however, when the age difference was of 2 decades or more, there was a significant difference in elastic fibers (P < 0.05). The difference in the number of blood vessels between the groups was not significant (P = 0.112). CONCLUSIONS: Aging promoted collagen reduction, fiber degradation and fragmentation, and increased disorganized elastic material density; however, it did not affect the number of dermal blood vessels.

Regulação autonômica das propriedades mecânicas em bioprótese valvar porcina / Autonomic regulation of mechanical properties in porcine mitral valve cusps / Regulación autonómica de las propiedades mecánicas en bioprótesis valvular porcina

FUNDAMENTO: A presença de nervos nas válvulas cardíacas foi demonstrada pela primeira vez há décadas e identificadas em subpopulações: simpáticas e parassimpáticas, e, portanto, é esperado que as válvulas sejam grandemente afetadas pelos nervos autônomos. Entretanto, poucos estudos têm se concentrado na regulação de válvulas cardíacas pelo sistema nervoso autônomo. OBJETIVO: Buscamos identificar o papel do sistema nervoso autônomo na regulação das propriedades mecânicas dos tecidos de válvulas mitrais porcinas. MÉTODOS: As propriedades mecânicas dos folhetos de válvulas mitrais porcinas foram avaliados em resposta à norepinefrina (NE) e acetilcolina (ACH), os principais neurotransmissores. Ao mesmo tempo, fentolamina (FENT), metoprolol (Metop), atropina (Atrop) e desnudamento endotelial foram adicionados ao sistema reativo. RESULTADOS: Sob condições fisiológicas, a rigidez não foi afetada pelo desnudamento endotelial (p > 0,05). A NE significantemente aumentou a rigidez valvar por aumento de 10 vezes na concentração (10-6 vs 10-7, p < 0,05; 10-5 vs 10-6, p < 0,05). Essa resposta foi amenizada por FENT, Metop ou desnudamento endotelial (p < 0,05); entretanto, manteve-se aumentada de maneira significante quando comparada aos Controles (p < 0,05). A ACH causou uma diminuição na rigidez acompanhada por um aumento em sua concentração (alteração significante na rigidez por aumento de 10 vezes na concentração de ACH, 10-6 vs Controle, p < 0,05; 10-5 vs 10-6, p < 0,05), que foi revertida pelo desnudamento endotelial e Atrop (p > 0,05 vs Controle). CONCLUSÃO: Esses achados ressaltam o papel do sistema nervoso autônomo na regulação das propriedades mecânicas das cúspides de válvula mitral porcina, o que reforça a importância do estado nervoso autônomo no funcionamento ideal da válvula.

BACKGROUND: The presence of nerves in heart valves was first depicted decades ago and identified into subpopulations: sympathetic, parasympathetic. So valves are expected to be greatly affected by the autonomic nerves. However, few studies have focused on the regulation of heart valves by the autonomic nervous system. OBJECTIVE: We sought to identify the role of the autonomic nervous system in the regulation of the mechanical properties of porcine mitral valve tissues. METHODS: Mechanical properties of porcine mitral valve leaflets were evaluated in response to norepinephrine (NE) and acetylcholine (ACH), the main neurotransmitters. At the same time, phentolamine (Phent), metoprolol (Metop), atropine (Atrop) and endothelial denudation were added to the reactive system. RESULTS: Under physiological conditions, the stiffness was not affected by endothelial denudation (p > 0.05). NE elevated the valve stiffness significantly per 10-fold increase in concentration (10-6 vs 10-7, p < 0.05; 10-5 vs 10-6, p < 0.05). This response was mitigated by Phent, Metop or endothelial denudation (p < 0.05), however, it was still increased significantly when compared to Controls (p < 0.05). ACH caused a decrease in stiffness accompanied by an increase in its concentration (significant change in stiffness per 10-fold increase in ACH concentration, 10-6 vs Control, p < 0.05; 10-5 vs 10-6, p < 0.05), which were reversed by endothelial denudation and Atrop (p > 0.05 vs Control). CONCLUSION: These findings highlight the role of the autonomic nervous system in the regulation of the mechanical properties of porcine mitral valve cusps, which underline the importance of autonomic nervous status for optimal valve function.

FUNDAMENTO: La presencia de nervios en las válvulas cardíacas quedó demostrada por primera vez hace algunas décadas e identificadas en sub-poblaciones: simpáticas y parasimpáticas y por lo tanto, lo que se espera es que las válvulas reciban una gran afectación de los nervios autónomos. Sin embargo, pocos estudios se han concentrado en la regulación de válvulas cardíacas a través del sistema nervioso autónomo. OBJETIVO: Buscamos identificar el papel del sistema nervioso autónomo en la regulación de las propiedades mecánicas de los tejidos de las válvulas mitrales porcinas. MÉTODOS: Las propiedades mecánicas de las capas de válvulas mitrales porcinas fueron evaluadas en respuesta a la norepinefrina (NE) y a la acetilcolina (ACH), los principales neurotransmisores. Igualmente, la fentolamina (FENT), el metoprolol (Metop), la atropina (Atrop) y la denudación endotelial también se añadieron al sistema reactivo. RESULTADOS: Bajo condiciones fisiológicas, la rigidez no se afectó por el denudación endotelial (p > 0,05). La NE aumentó significativamente la rigidez valvular con un aumento de 10 veces en la concentración (10-6 vs 10-7, p < 0,05; 10-5 vs 10-6, p < 0,05). Esa respuesta fue amenizada por FENT, Metop o denudación endotelial (p < 0,05); pero se mantuvo aumentada de manera significativa cuando se le comparó con los Controles (p < 0,05). La ACH causó una disminución en la rigidez acompañada por un aumento en su concentración (alteración significativa en la rigidez por el aumento en 10 veces de la concentración de ACH, 10-6 vs Control, p < 0,05; 10-5 vs 10-6, p < 0,05), que fue revertida por la denudación endotelial y Atrop (p > 0,05 vs Control). CONCLUSIÓN: Esos hallazgos destacan el rol del sistema nervioso autónomo en la regulación de las propiedades mecánicas de las cúspides de la válvula mitral porcina, lo que refuerza la importancia del estado nervioso autónomo en el funcionamiento ideal de la válvula.

The functions of the fibre bundles of the anterior cruciate ligament in anterior drawer, rotational laxity and the pivot shift.

This paper reviews the functional anatomy of the anterior cruciate ligament (ACL), which has a parallel array of collagen fascicles that have usually been divided into two 'fibre bundles': anteromedial (AM) and posterolateral (PL), according to their tibial attachment sites. The PL bundle has shorter fibres, and so it is subjected to greater tensile strains than the AM bundle when the whole ACL is stretched; its oblique orientation in the coronal plane imbues it with greater ability to resist tibial rotation than the more vertical AM fibre bundle. Most studies have found that the AM bundle is close to isometric when the knee flexes, while the PL bundle slackens approximately 6 mm. There is little evidence of significant fibre bundle elongation in response to tibial rotation. Selective bundle cutting studies have been performed, allowing both the bundle tensions and their contributions to resisting tibial anterior translation and tibial rotation to be calculated. These show that the function of the PL bundle was dominant near knee extension in some studies, particularly when resisting anterior drawer and that its contribution reduced rapidly with knee flexion through 30 degrees. There has been little study of the contributions of the fibre bundles in control of tibial internal-external rotation or the pivot shift: one study found that the AM bundle had larger tensions than the PL bundle during a simulated pivot shift, but another study found that cutting the PL bundle allowed a larger increase in coupled tibial anterior translation than cutting the AM bundle. It was concluded that the AM bundle is most important for resisting tibial anterior drawer-the primary function of the ACL-while the PL bundle is tight near knee extension, when it has a role in control of tibial rotational laxity. There is a clear need for further study of dynamic knee instability, to gain better understanding of how best to reconstruct the ACL and associated tissues.

Fibroelastic components of the vesicourethral junction of rats in the aging process / Componentes fibroelásticos de la unión vesicouretral de ratas en el proceso de envejecimiento

The vesicourethral junction comprising the vesical trigone, is relevant in setting and positioning of the urinary bladder, along with the vesical neck, fixed by lateral ligaments of the bladder and tendinous arch of the pelvis fascia. Namely,the puboprostatic ligament (men) and the pubovesical (women). The circular set elastic fibers in this junction are important and valuable in the elasticity and plasticity of the area, allowing quick expansion and withdrawal with the flow of urine, and associated to smooth muscle tissue and nerve control form an important collective to maintain urinary continence. The objective of the present study is to describe the elastic system in the vesicouretral junction in relation to aging and its involvement in the states of urinary continence and incontinence, as well as the study of the vesicouretral junction in various age groups while evaluating with electron transmission microscopy. To carry out the study, 12 Wistar rats were used, divided into groups: neonate (4 animals), adult group (4 animals) and aged group (4 animals). Electron transmission microscopy with use of tanic acid technique associated to glutaraldehyde fixation, satisfactorily showed the extreme structural differences between mature elaunin and oxytalan fibers present between intercelular spaces and bundles of collagen fibers. The phases of elastogenesis in neonate animals and degradation of the elastic system of older animals were also evaluated.

La unión vesico-uretral, componente del trígono vesical, posee una relevante importancia en la fijación y posicionamiento de la vejiga urinaria conjuntamente con el cuello vesical, fijado por los ligamentos laterales de la vejiga y arco tendinoso de la fascia de la pelvis. Principalmente, sus componentes anteriores son: el ligamento puboprostático en los hombres y el ligamento pubovesical en las mujeres. Las fibras elásticas dispuestas circularmente en esta unión, son de valiosa importancia en la elasticidad y plasticidad de la región, permitiendo expansión y retiro rápido con el flujo de la orina, y asociado a musculatura lisa y control nervioso forman un conjunto importante para el mantenimiento de la continencia urinaria. Debido a existencia de puntos no esclarecidos en esta región en relación al sistema elástico y su participación en los estados de continencia/incontinencia urinaria, el presente trabajo tiene por objetivo el estudio de la unión vesico-uretral evaluándola en diferentes grupos etarios, a través de la microscopía electrónica de transmisión. Fueron utilizados 12 ratones Wistar, divididos en grupo de neonatos (4 animales), grupo adulto (4 animales) y grupo de ratones viejos (4 animales). La microscopía electrónica de transmisión, con uso de la técnica del ácido tánico asociado al fijador glutaraldeído, mostró satisfactoriamente las diferencias ultraestructurales entre las fibras elásticas maduras, elaunínicas y oxitalánicas, presentes entre los espacios intercelulares de las células musculares y haces de fibras colágenas, y también fases de elastogénesis en animales neonatos y envejecimiento y degradación del sistema elástico en los animales mayores.

Corneal biomechanical evaluation in healthy thin corneas compared with matched keratoconus cases / Análise da biomecânica corneana em córneas finas saudáveis comparadas com pacientes com ceratocone pareados por espessura corneana, sexo e idade

PURPOSE: To evaluate and compare corneal hysteresis (CH) and corneal resistance factor (CRF) in healthy eyes with a central corneal thickness (CCT) < 505 µm with CH and CRF in gender-, age-, and CCT-matched keratoconus cases, and to estimate the sensitivity and specificity of these parameters for discriminating between the two groups. METHODS: Prospective, comparative case series. In total 46 eyes from 30 healthy patients with CCT < 505 µm, and 42 eyes from 30 CCT-, gender- and age-matched keratoconus cases were enrolled. Biomechanical metrics (CH and CRF) were measured using the Ocular Response Analyzer (ORA) and then compared. A receiver operating characteristic (ROC) curve was used to identify cut-off points to maximize the sensitivity and specificity for discriminating between the groups. RESULTS: The CCT was 485.96 ± 17.61 µm (range, 438 - 505) in healthy thin corneas and 483.64 ± 16.19 µm (range, 452 - 505) in keratoconus; p=0.5225. CH was 8.63 ± 1.23 mmHg (range, 5.95 - 12.2) and 8.07 ± 1.17 mmHg (range, 4.9 - 9.85), respectively; p=0.0312. CRF was 8.43 ± 1.29 mmHg (range, 5.45 - 11.10) and 7.22 ± 1.34 mmHg (range, 4.7 - 9.45), respectively; p<0.001. ROC curve analysis showed a poor overall predictive accuracy of CH (cut-off, 8.95 mmHg; sensitivity, 63 percent; specificity, 23.8 percent; test accuracy, 44.30 percent) and CRF (cut-off, 7.4 mmHg; sensitivity, 28.3 percent; specificity, 40.5 percent; test accuracy, 34.12 percent) for detecting keratoconus in the eyes studied. CONCLUSION: CH and CRF were statistically lower in keratoconus than in healthy thin corneas. However, CH and CRF offered very low sensitivity and specificity for discriminating the groups.

OBJETIVO: Avaliar e comparar a histerese corneana (CH) e o fator de resistência corneano (CRF) em olhos saudáveis com espessura corneana central (CCT) < 505 µm com os resultados de CH e CRF em pacientes com ceratocone pareados por sexo, idade e CCT, além de estimar a sensibilidade e especificidade destes parâmetros na diferenciação dos grupos. MÉTODOS: Estudo prospectivo, do tipo série de casos comparativa. No total, 46 olhos de 30 pacientes saudáveis com CCT < 505 µm, e 42 olhos de 30 pacientes com ceratocone pareados por sexo, idade e CCT foram incluídos. Os parâmetros biomecânicos (CH e CRF) foram obtidos através do equipamento Ocular Response Analyzer (ORA) e depois comparados. Curvas ROC (Receiver operating characteristic) foram utilizadas para identificar o melhor valor de corte que apresentasse a maior sensibilidade e especificidade na discriminação entre ceratocone e córneas finas saudáveis para cada dado estudado. RESULTADOS: A CCT encontrada foi 485,96 ± 17,61 µm (de 438 a 505) no grupo de córneas finas saudáveis e 483.64 ± 16,19 µm (de 452 a 505) no grupo ceratocone; p=0,5225. CH 8,63 ± 1,23 mmHg (de 5,95 a 12,2) e 8,07 ± 1,17 mmHg (de 4,9 a 9,85), respectivamente; p=0,0312. CRF 8,43 ± 1,29 mmHg (de 5,45 a 11,10) e 7,22 ± 1,34 mmHg (de 4,7 a 9,45), respectivamente; p<0,001. Análise das curvas ROC mostrou baixa acurácia na diferenciação das córneas finas saudáveis daquelas com ceratocone tanto para CH (ponto de corte, 8,95 mmHg; sensibilidade, 63 por cento; especificidade, 23,8 por cento; acurácia, 44,30 por cento) quanto para CRF (ponto de corte, 7,4 mmHg; sensibilidade, 28,3 por cento; especificidade, 40,5 por cento; acurácia, 34,12 por cento). CONCLUSÃO: Dados fornecidos pelo ORA (CH e CRF) mostraram-se estatisticamente mais baixos em pacientes com ceratocone quando comparados com córneas finas de indivíduos saudáveis. No entanto, os dois parâmetros biomecânicos estudados apresentaram sensibilidade e especificidade muito baixas na diferenciação dos grupos.

Imaging the elastic properties of tissue: the 20 year perspective.

After 20 years of innovation in techniques that specifically image the biomechanical properties of tissue, the evolution of elastographic imaging can be viewed from its infancy, through a proliferation of approaches to the problem to incorporation on research and then clinical imaging platforms. Ultimately this activity has culminated in clinical trials and improved care for patients. This remarkable progression represents a leading example of translational research that begins with fundamentals of science and engineering and progresses to needed improvements in diagnostic and monitoring capabilities applied to major categories of disease, surgery and interventional procedures. This review summarizes the fundamental principles, the timeline of developments in major categories of elastographic imaging, and concludes with recent results from clinical trials and forward-looking issues.

Elastic laminae in vascular development and disease.

The activities of vascular cells, including adhesion, proliferation, and migration, are mediated by extracellular matrix components, including collagen matrix and elastic fibers or laminae. Whereas the collagen matrix stimulates vascular cell adhesion, proliferation, and migration, the elastic laminae inhibit these activities. Coordinated regulation of cell activities by these matrix components is an essential process for controlling the development and remodeling of the vascular system. This article summarizes recent development on the role of arterial elastic laminae in regulating the development of smooth muscle-like cells from bone marrow-derived progenitor cells as well as in mediating cell adhesion, proliferation, and migration with a focus on the molecular mechanisms and physiological significance.

Changes in ocular response analyzer parameters after LASIK.

PURPOSE: To investigate changes in Ocular Response Analyzer parameters after myopic LASIK. METHODS: Thirty myopic patients (60 eyes) undergoing bilateral LASIK were studied prospectively. Corneal hysteresis, corneal resistance factor, Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated IOP (IOPcc) measurements were obtained with the Ocular Response Analyzer before and after LASIK. Central corneal thickness and corneal flap thickness were also measured with optical coherence tomography. RESULTS: Compared with preoperative baseline values, corneal hysteresis, corneal resistance factor, IOPg, IOPcc, and central corneal thickness decreased postoperatively (P<.01). Corneal hysteresis (CH), corneal resistance factor (CRF), IOPg, IOPcc, and central corneal thickness (CCT) increased between 10 days and 3 months (post-hoc, P<.05). (The differences between the preoperative values and those at 3 months postoperatively are denoted by Delta.) The correlation of the ablation depth was stronger for DeltaCRF (r=0.457) than for DeltaCH (r=0.271). DeltaCH was negatively correlated to flap thickness (r=-0.361) and the ratio of flap thickness to preoperative central corneal thickness (r=-0.442) whereas DeltaCRF was not. DeltaCH was positively correlated with DeltaIOPcc, and DeltaCRF was positively correlated with DeltaIOPg. DeltaIOPg was positively correlated with DeltaCCT whereas DeltaIOPcc was not. CONCLUSIONS: Corneal biomechanical properties measured by corneal hysteresis and corneal resistance factor were decreased at 10 days after LASIK. Minimal recovery (approximately 10% of the changes) was achieved by 3 months. The changes in biomechanical properties may affect IOP measurement.

Finite element modeling of corneal biomechanical behavior.

PURPOSE: To optimize the construction details of corneal numerical models while maintaining efficiency and reliability of predictions. METHODS: Nonlinear finite element analysis of corneal models was carried out to assess the importance of considering the cornea's hyperelastic, hysteretic and anisotropic behavior, multi-layer construction, weak inter-lamellar adhesion, non-uniform thickness, elliptical topography, and connection to the sclera. The effect of each of these parameters was determined by removing it from the numerical models and assessing the effect on the results. This exercise was carried out under two load cases--a uniform posterior pressure subjecting the cornea to predominantly membrane tension stresses, and a concentrated anterior pressure as applied by the Ocular Response Analyzer (Reichert Ophthalmic Instruments), which creates mainly bending stresses. RESULTS: Corneal models subjected to mainly bending stresses were particularly sensitive to simplifications in modeling corneal nonuniform thickness, weak interlamellar adhesion, and multi-layer construction. On the other hand, models under mainly membrane tension were more sensitive to simplifications in elliptical profile and connection to the sclera. Considering hyper-elasticity was important in both cases. Hysteresis was also important, but only in applications involving load reversal. CONCLUSIONS: Although simplifications may be necessary to reduce the cost of numerical model construction and analysis, the selection of which simplifications to adopt should be done with care. They should only be considered when their effect on results is acceptably small, and their inclusion does not make the model significantly different from real-life conditions.

Pentoxifylline attenuates transforming growth factor-ß1-stimulated collagen deposition and elastogenesis in human tunica albuginea-derived fibroblasts part 1: impact on extracellular matrix.

INTRODUCTION: Transforming growth factor-ß1 (TGF-ß1) has been implicated in the pathogenesis of Peyronie's disease (PD) and also plays a role in collagen and elastin metabolism. Pentoxifylline (PTX) antagonizes the effects of TGF-ß1 and has been utilized in our clinic for the management of PD. AIM: We studied the effects of TGF-ß1 and PTX on collagen metabolism and elastogenesis in tunica albuginea-derived fibroblasts (TADFs). METHODS: TADFs from men with and without PD were cultured and treated with TGF-ß1 and PTX as monotherapy at differing concentrations and time points. Combination treatment (TGF-ß1 followed by PTX and vice versa) was also investigated. MAIN OUTCOME MEASURES: Cell proliferation assay, enzyme-linked immunosorbent assay, and immunohistochemistry were utilized to assess the impact of TGF-ß1 and PTX on TADF with respect to elastin and collagen I metabolism. RESULTS: PTX inhibited fibroblast proliferation at doses of 100 µM. TGF-ß1 stimulated elastogenesis and collagen I fiber deposition in TADF in a dose- and time-dependent fashion. Pretreatment with PTX dramatically attenuated TGF-ß1-mediated elastogenesis and collagen fiber deposition in TADF from men with and without PD. Interestingly, production of collagen I was higher in untreated Peyronie's tunica (PT) cells relative to normal tunica (NT) cells; furthermore, PTX attenuated collagen production to levels similar to untreated control TADF in PT cells but not in NT cells, suggesting important intrinsic differences between PT and NT cells. CONCLUSION: Both elastin and collagen are upregulated by TGF-ß1 in TADF. This likely contributes to the PD phenotype. Pretreatment with PTX attenuates both collagen fiber deposition and elastogenesis in TADF exposed to TGF-ß1; these effects suggest a useful role for PTX in the management of PD.