12 research outputs found
Attenuation of Salt-Induced Cardiac Remodeling and Diastolic Dysfunction by the GPER Agonist G-1 in Female mRen2.Lewis Rats
The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH) on cardiac function and structure.Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS) diet or a high salt (4% sodium; HS) diet for 10 weeks beginning at 5 weeks of age.Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV) diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope), increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e')] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05) as determined by tissue Doppler.Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure
Tension lines of the skin
Skin tension lines are natural lines of tension that occur within the skin as a result of growth and remodeling mechanisms. Researchers have been aware of their existence and their surgical implications for over 150 years. Research in the twentieth century showed clearly, through destructive mechanical testing, that the orientation of skin tension lines greatly affects the mechanical response of skin in situ. More recent work has determined that this anisotropic response is, at least in part, due to the structural arrangement of collagen fibres within the dermis. This observation can be incorporated into mathematical and mechanical models using the popular Gasser-Ogden-Holzapfel constitutive equation. Advances in non-invasive measurement techniques for the skin, such as those based on elastic wave propagation, have enabled patient-specific identification of skin tension lines in an accurate and rapid manner. Using this technique on humans, we show that there is considerable variation in the level of anisotropy as the skin ages. Furthermore, we identify that both the structural arrangement of fibres and the in vivo levels of pre-strain play a significant role in the anisotropic behavior of skin.Peer reviewed2021-05-2
Tension lines of the skin
Skin tension lines are natural lines of tension that occur within the skin as a result of growth and remodeling mechanisms. Researchers have been aware of their existence and their surgical implications for over 150 years. Research in the twentieth century showed clearly, through destructive mechanical testing, that the orientation of skin tension lines greatly affects the mechanical response of skin in situ. More recent work has determined that this anisotropic response is, at least in part, due to the structural arrangement of collagen fibres within the dermis. This observation can be incorporated into mathematical and mechanical models using the popular Gasser-Ogden-Holzapfel constitutive equation. Advances in non-invasive measurement techniques for the skin, such as those based on elastic wave propagation, have enabled patient-specific identification of skin tension lines in an accurate and rapid manner. Using this technique on humans, we show that there is considerable variation in the level of anisotropy as the skin ages. Furthermore, we identify that both the structural arrangement of fibres and the in vivo levels of pre-strain play a significant role in the anisotropic behavior of skin.Peer reviewed2021-05-2
Differences in Tendon Graft Healing Between the Intra-articular and Extra-articular Ends of a Bone Tunnel
The basic biology of healing between a tendon graft and bone tunnel remains incompletely understood. Distinct variability in the morphological characteristics of the healing tendon–bone attachment site has been reported. We hypothesized that spatial and temporal differences in tendon-to-bone healing exist at different regions of a surgically created bone tunnel. Twenty-four male, Sprague–Dawley rats underwent anterior cruciate ligament (ACL) reconstruction in the left knee using a flexor digitorum longus tendon graft secured using suspensory periosteal fixation. Animals were sacrificed at 4, 7, 11, 14, 21, and 28 days after surgery and prepared for routine histology and immunohistochemical analysis of the healing enthesis at the intra-articular aperture (IAA), mid-tunnel, and extra-articular aperture (EAA). Six animals were used to measure mineral apposition rate (MAR) along the healing bone tunnel by double fluorochrome labeling at 14 and 28 days after surgery. The total area of calcified bone matrix was assessed with von Kossa staining and Goldner-Masson trichrome staining, respectively. The healing tendon–bone interface tissue exhibited a wide chondroid matrix at the IAA, in contrast to a narrow, fibrous matrix at the EAA. There were significantly more osteoclasts at the IAA compared to EAA throughout the study period, except 4 days after surgery (p < 0.05). Collagen continuity between the tendon graft and bone tunnel increased over time, with a more parallel orientation and increased collagen fiber continuity between tendon and bone at the EAA compared to the IAA. MAR was also significantly greater at the EAA at 4 weeks (p < 0.001). Significant differences in healing between the tendon graft and bone exist along the length of bone tunnel secured with suspensory fixation. The etiology of these differences is likely multifactorial in nature, including variable biological and biomechanical environments at different ends of the tunnel. Understanding these differences may ultimately allow surgeons to improve the quality of graft fixation and long-term outcomes after ACL reconstruction
Pulsed electromagnetic field (PEMF) promotes collagen fibre deposition associated with increased myofibroblast population in the early healing phase of diabetic wound
Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents
Background: Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans. Methods: Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort - matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves - pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale. Results: Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B=.97 [95% CI:. 16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected. Conclusions: This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain