Preventive and therapeutic effects of relaxin on bisphosphonate related osteonecrosis of the jaw: an experimental study in rats / Efeitos preventivos e terapêuticos da relaxina na osteonecrose da mandíbula relacionada a bisfosfonatos: um estudo experimental em ratos

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of chronic bisphosphonate (BP) use. The hormone relaxin is able to induce the multistep differentiation process of human osteoclastogenesis, exhibits antifibrotic and anti-inflammatory actions, and promotes vasodilatation, wound healing, and angiogenesis. The present study aimed to evaluate the effects of relaxin in the prevention and management of BRONJ. Material and Methods: Thirty-six male Sprague Dawley rats were randomly divided into four groups. Rats in group 1 (n = 10) received relaxin and BP simultaneously for 12 weeks. Rats in group 2 (n = 10) received injections of BP for 12 weeks, followed by relaxin for another 12 weeks. Rats in group 3 (n = 10) received only BP injections, and those in group 4 (control, n = 6) received only saline. Necrosis and inflammation in the rats' mandibles were evaluated as indicators of BRONJ. Results: Necrosis and inflammation were not detected in group 1 (BP + relaxin). In group 3 (BP only), incidence rates of necrosis and inflammation were 90% and 60%, respectively. Conclusions: Our findings suggest that relaxin may be potently effective in preventing BRONJ and have some benefit in the treatment of existing BRONJ (AU)

Objetivo: A osteonecrose da mandíbula relacionada ao bisfosfonato (BRONJ) é uma desafiadora complicação do uso crônico de bisfosfonato (BP). O hormônio relaxina é capaz de induzir o processo múltiplo de diferenciação da osteoclastogênese humana, exibe ações anti-fibróticas e anti-inflamatórias e promove vasodilatação, cicatrização de feridas e angiogênese. O presente estudo teve como objetivo avaliar os efeitos da relaxina na prevenção e tratamento do BRONJ. Material e Métodos: Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em quatro grupos. Os ratos do grupo 1 (n = 10) receberam relaxina e BP simultaneamente por 12 semanas. Os ratos do grupo 2 (n = 10) receberam injeções de BP por 12 semanas, seguidos de relaxina por mais 12 semanas. Os ratos do grupo 3 (n = 10) receberam apenas injeções de BP e os do grupo 4 (controle, n = 6) receberam apenas solução salina. Necrose e inflamação nas mandíbulas dos ratos foram avaliadas como indicadores de BRONJ. Resultados: Necrose e inflamação não foram detectadas no grupo 1 (BP + relaxina). No grupo 3 (somente BP), as taxas de incidência de necrose e inflamação foram de 90% e 60%, respectivamente. Conclusões: Nossos resultados sugerem que a relaxina pode ser potentemente eficaz na prevenção do BRONJ e ter algum benefício no tratamento do BRONJ existente.(AU)

Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model

PURPOSE: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.

Effect of recombinant human relaxin on regulating protein kinase G in myocardial tissue taken from a rabbit diastolic heart failure model / 中华老年心脑血管病杂志

Objective To study the effect of recombinant human relaxin (RLX) on regulating the protein kinase G (PKG) in myocardial tissue taken from a rabbit diastolic heart failure (DHF) model.Methods A DHF model of rabbits was established by constricting their abominal aorta.Twenty-eight New Zealand rabbits were randomly divided into sham operation group (n =6),DHF group (n=6),30 μg/kg · d RLX group (n=8),98 μg/kg · d RLX group (n=8).The animals were treated with RLX for 2 weeeks.Serum samples were taken at week 10 after operation for measuring the serum levels of BNP,RLX,3-NT,NO,cGMP and PKG by ELISA.Results The serum levels of BNP and 3-NT were significantly higher while those of NO,cGMP and PKG were significantly lower in DHF group,30 μg/kg · d RLX group and 98 μg/kg · d RLX group than in sham operaion group (P＜0.05).The serum levels of NO,cGMP and PKG were significantly higher while those of 3-NT were significantly lower in 98 μg/kg · d RLX group than in DHF group (P＜0.05).Conclusion Large RLX dose alleviates the left ventricular diastolic function and oxidative stress,increases the bioavailability of NO and the activity of PKG through the signal pathaway of NO,cGMP,PKG,and can thus prevent myocardial fibrosis and improve the left ventricular diastolic function in DHF rabbits.

Study on relationship between interaction of estrogen, progesterone and relaxin with stress urinary incontinence during pregnancy / 重庆医学

Objective To study the relationship between the expression levels of estrogen,progesterone,relaxin(RLX) and expression levels of vaginal wall hormone receptors in late pregnancy with stress urinary incontinence(SUI) during pregnancy.Methods Ninety-three healthy pregnant women were selected from July 2014 to November 2015,including 47 cases in the SUI group and 46 cases in the non-SUI group.The blood sample was collected at 37-40 weeks gestation.The levels of serum E2,E3,P and RLX were respectively detected by using the chemiluminescence immunoassay and enzyme linked immunosorbent assay(ELISA).The full thickness tissues of posterior vaginal wall were obtained at delivery in 42 cases of the SUI group and 44 cases of the non-SUI group,and the expressions of ER,PR and LGR7 in pelvic floor tissues were detected by immunohistochemical staining.Results There was no statistically significant difference in serum E2,E3 and P levels between the SUI group and the non-SUI group(P＞0.05);the serum RLX level of the SUI group was significantly higher than that of the non-SUI group(P＜0.05).The positive expression intensity of ER in pelvic floor tissue of the SUI group was lower than that of the non-SUI group(P＜0.05),the positive expression intensity of PR and LGR7 in the SUI group was higher than that in the non-SUI group(P＜0.05).The serum RLX level and expression of LGR7 in pelvic floor tissues of pregnant women had no correlation with E2,E3 and P(P＞0.05).The LGR7 level in pelvic floor tissues had no correlation with ER,and was positively correlated with PR.Conclusion In late pregnancy,the biological activity of estrogen,progesterone and RLX on pelvic floor support tissues is mediated by their receptors expression levels,the progesterone receptor may have a positive regulation effect on LGR7,which is closely related to the occurrence of SUI in pregnancy.

Effects of recombinant human relaxin-2 on hepatic stellate cell proliferation, synthesis of Collagen Ⅰ,and mRNA expressions of TGF-β1 and CTGF in vitro / 西安交通大学学报(医学版)

ABSTRACT:Objective To validate that relaxin can resist hepatic fibrosis at the cellular level and explore its molecular mechanism in order to provide experimental basis for the treatment of liver cirrhosis.Methods Cultured HSC-T6s were treated with different concentrations (20,50 and 100 ng/mL)of recombinant human relaxin-2 (RLX-2).The proliferation of HSC-T6 was measured by MTT colorimetric assay.The content of type Ⅰcollagen in the cell culture supernatant of each group was detected by ELISA at 48 h of drug intervention;RT-PCR was used to detect the mRNA expressions of CTGF and TGF-β1 in HSC-T6 at 48 h of drug intervention.Results RLX-2 inhibited the proliferation of HSC and reduced type Ⅰ collagen content of HSC cells.It also inhibited the CTGF mRNA expression of HSC,but did not have a significant effect on the expression of TGF-β1 mRNA. Conclusion In the experiment of culturing HSC-T6 in vitro,RLX-2 may play a role in rat liver fibrosis by inhibiting cell proliferation and type Ⅰ collagen and CTGF mRNA expressions.

Relaxin Modulates the Expression of MMPs and TIMPs in Fibroblasts of Patients with Carpal Tunnel Syndrome

PURPOSE: The aim of this study was to investigate the anti-fibrotic effect of relaxin in subsynovial fibroblasts activated by transforming growth factor beta (TGF-β). MATERIALS AND METHODS: To test the anti-fibrotic effect of an adenovirus-relaxin construct (Ad-RLN) on subsynovial fibroblasts in vitro, cells from subsynovial connective tissue of patients with carpal tunnel syndrome were activated with TGF-β1 and exposed to Ad-RLN (as a therapeutic gene) or adenovirus-lacZ construct (as a marker gene) for four hours. Subsynovial fibroblast cultures without adenoviral exposure served as controls. RESULTS: We observed induction of gene expressions of collagen I, III and IV, as well as the abatement of alpha-smooth muscle actin (a-SMA) synthesis, Smad2 phosphorylation, and fibronectin at the protein level, in comparison to controls. In addition, protein expressions of matrix metalloproteinase (MMP) I was significantly induced, whereas the protein expressions of tissue inhibitor of metalloproteinases (TIMP) I and IV were reduced due to relaxin expression. CONCLUSION: RLN prevents excessive synthesis of extracellular matrix by reducing the expressions of its components, such as fibronectin, a-SMA, and phosphorylated Smad2, by increasing the expression of MMPs; and by decreasing the expression of TIMPs.

Effect of Relaxin Expressing Adenovirus on Scar Remodeling: A Preliminary Study

BACKGROUND: Relaxin is a transforming growth factor β1 antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. METHODS: Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. RESULTS: Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. CONCLUSION: Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated.

Role of Relaxin-2 in the migration of human vascular smooth muscle cells and its underlying mechanisms / 重庆医学

Objective To investigate the effect and the associated mechanism of Relaxin‐2 in the migration of human vascular smooth muscle cells (VSMCs) .Methods The migration of VSMCs in responsing to Relaxin‐2 was evaluated by using wound heal‐ing assay and transwell assay ,and the cell signaling proteins ,including Akt ,ERK and NF‐κB p65 ,in responsing to Relaxin‐2 were measured by using Western blotting assay .Results Relaxin‐2 can promote the migration of VSMCs in a dose‐dependent manner , NF‐κB inhibitor BAY11‐7082 can block the expression of MMP‐9 and MMP‐2 induced by Relaxin‐2 ,pretreatment with PI3K inhibi‐tor LY294002 and ERK inhibitor U0126 can reduce the activation of NF‐κB p65 induced by Relaxin‐2 .Conclusion NF‐κB p65 could be activated by the activation of PI3K/Akt and ERK signaling pathway induced by Relaxin‐2 ,thereby promoting the expression of MMP‐9 and MMP‐2 ,and inducing VSMCs migration effect .

Expression of relaxin family peptide receptor 1 in the lung tissue of silicosis rats / 中国职业医学

OBJECTIVE: To investigate the potential effect of relaxin family peptide receptor 1( RXFP1) in the process of silica-induced silicosis. METHODS: Sixty-four specific pathogen free male Wistar rats were randomly divided into control group and experimental group. By one time intratracheal infusion,rats in experimental group were treated with 0. 1 m L 500 g / L silica dust suspension while the control group was treated with 0. 1 m L sodium chloride physiological solution. Eight rats from each group were sacrificed on day 1,7,14 and 28 after exposure. Histopathologic changes of the lung tissue were performed with hematoxylin-eosin staining. The expressions of Rxfp1 mRNA and RXFP1 protein in rat lungs were detected by real-time polymerase chain reaction and immunohistochemical staining,respectively. RESULTS: After 28 days of exposure,the grey nodules were observed by naked eye in the lung of the experimental group. The fracture and silicotic nodules could be seen in alveolar interval with light microscope. Compared with the control group,the Rxfp1 mRNA relative expression level in the lungs of experimental group was increased to 145% after 1 day of exposure( P < 0. 01),followed by a decrease on day 7 and 14 and reached similar level of control group( P > 0. 05). By day 28,it dropped to45% of control group( P < 0. 01). The RXFP1 protein relative expression in experimental group was significantly up-regulated since the 7th day compared to that of the control group( P < 0. 01). And it reached to the highest level on the28 th day( P < 0. 01). CONCLUSION: The RXFP1 might play an important role in inhibiting silicosis.

Relaxin Receptor RXFP1 and RXFP2 Expression in Ligament, Tendon, and Shoulder Joint Capsule of Rats

Numerous musculoskeletal disorders are caused by thickened ligament, tendon stiffness, or fibrosis of joint capsule. Relaxin, a peptide hormone, can exert collagenolytic effect on ligamentous and fibrotic tissues. We hypothesized that local injection of relaxin could be used to treat entrapment neuropathy and adhesive capsulitis. Because hormonal effect depends on the receptor of the hormone on the target cell, it is important to confirm the presence of such hormonal receptor at the target tissue before the hormone therapy is initiated. The aim of this study was to determine whether there were relaxin receptors in the ligament, tendon, and joint capsular tissues of rats and to identify the distribution of relaxin receptors in these tissues. Transverse carpal ligaments (TCLs), inguinal ligaments, anterior cruciate ligaments (ACLs), Achilles tendons, and shoulder joint capsules were obtained from male Wistar rats. Western blot analysis was used to identify relaxin receptor isoforms RXFP1 and RXFP2. The distribution of relaxin receptors was determined by immunohistochemical staining. The RXFP1 isoform was found in all tissues examined. The RXFP2 isoform was present in all tissues but the TCLs. Its expression in ACLs tissues was relatively weak compared to that in other tissues. Our results revealed that RXFP1 and RXFP2 were distributed in distinctly different patterns according to the type of tissue (vascular endothelial cells, fibroblast-like cells) they were identified.

Study of the effect and mechanism of relaxin on the ECM excretion of Human renal mesangial cells cultured in high ambient glucose / 中国医师杂志

Objective To explore the effect and mechanism of relaxin on the production of extracellular matrix (ECM) excreted by high glucose stimulated human renal mesangial cells.Methods Cultured human mesangial cells (HMCs) were divided into three groups:(1) normal glucose group (NG,5.5 mmol/L D-glucose),(2) high glucose group (HG,30 mmol/L D-glucose),and (3) high glucose + relaxin group.Cell count kit (CCK8) was used to examine the cell proliferation.The levels of fibronectin and collagen type Ⅳ in the culture supernatants were examined with a solid-phase enzyme-linked immunoadsorbent assay (ELISA);Western blot method was used to detect the expression of α-smooth muscle actin (α-SMA) protein.The transforming growth factor-β1 (TGF-β1) mRNA expression was detected with quantitative polymerase chain reaction (qPCR) method.Results No proliferation and inhibition effects were observed in both normal and high glucose group.Compared to the normal glucose group,the levels of fibronectin,and collagen type Ⅳ increased significantly (57.28 ± 0.59 vs 41.85 ± 0.03,56.52 ± 0.88 vs 33.80 ± 0.24,P ＜ 0.01)after cultured 48 h in high concentration of glucose.Compared to the high glucose group,a significantly decreases of fibronectin and collagen type Ⅳ (47.08 ± 0.03 vs 57.28 ± 0.59,36.16 ± 0.52 vs 56.52 ±0.88,P ＜0.01) were observed in the relaxin treated group.The expressions of α-smooth muscle actin and TGF-β1 were decreased (P ＜0.01).Conclusions Relaxin can suppress the overproduction of ECM excreted by HMC cultured in high ambient glucose,and its mechanism is partly due to the inhibition of TGF-β1.

Mechanism of Ligamentum Flavum Hypertrophy / 대한정형외과연구학회지

Ligamentum flavum (LF) is yellowish ligament tissue connecting the lamina of adjacent vertebra. Degenerative changes in the spine cause the hypertrophy of LF and facet joint and disc bulging and herniation. These changes results in a narrowing of the spinal canal. Neural decompression surgery by removing the hypertrophied lamina, LF and disc pathologies has been considered as successful treatment method in lumbar spinal stenosis. This surgery has showed relatively satisfactory clinical results and has increased life-expectancy in elderly patients. However, issues about post spinal surgery syndrome and re-stenosis after the surgery also have been reported. Because LF is one of the main mechanisms of spinal stenosis, accurate understanding about pathologic mechanism on the LF hypertrophy may suggest alternative treatment methods such as medical treatment or less invasive treatment than surgical decompression can be considered. Hypertrophy of the ligamentum flavum is generated from increase of collagen synthesis, fibroblast proliferation, and fibrosis caused by 1) the expression of growth factors (TGF-beta1 etc.) stimulated by the repeated mechanical tension, 2) inflammatory cytokines from spinal facet joint structure and LF 3) delayed cell death, and 4) inflammatory cytokine from hypertrophied and degenerated LF itself. After the middle ages, gradual and partial inhibition of LF hypertrophy can be expected by administration NSAIDs or selective cyclo-oxygenase-2 inhibitors because these drugs may cause reduction of the increased cytokines. Also, relaxin can be another new treatment material for spinal stenosis by the mechanism of melting hypertrophied LF and reducing synthesis of collagen.

Cultura de células da granulosa humanas com fenótipo de fase folicular: influência do sistema quimicamente definido na morfologia, ultraestrutura, secreção de esteroides e relaxina / Culture of human granulosa cells with follicular phase phenotype:influence of chemically defined system on morphology, ultrastructure,secretion of steroids and relaxin

Está bem descrito na literatura o padrão de cultivo de células da granulosa (CG) humanas que perpetua a luteinização, simulando a fase lútea do ciclo. Nesse sistema, há redução na secreção de estradiol (E2) e aumento na síntese de progesterona (P4) e relaxina (RLN). Objetivamos padronizar um sistema de cultura livre de soro, com o intuito de reverter o processo de luteinização de CG obtidas em ciclos de fertilização in vitro (FIV), pré-luteinizadas pela gonadotrofina coriônica humana (hCG), para aplicação na maturação in vitro de folículos ovarianos pré-antrais. Foi feito estudo experimental com GC obtidas de 10 mulheres em tratamento de reprodução assistida. As CG foram cultivadas em α-MEM contendo IGF-I, ITS, androstenediona, PVP-40 (meio quimicamente definido) ou TCM-199 contendo FSH/soro. Após 48, 96 e 144 horas, foram avaliados: morfologia das culturas, produção de E2, P4 (Quimioluminescência/Immulite), RLN (Elisa) e ultraestrutura (Microscopia Eletrônica). Os dados foram analisados por Anova e regressão linear com efeitos mistos (SAS versão 9.0). Células cultivadas em α-MEM apresentam alta capacidade estrogênica e padrão de produção hormonal característico da fase folicular, mantendo características morfológicas/ultraestruturais semelhantes a células in vivo. No sistema de cultura padronizado, as CG não completam in vitro o processo de luteinização deflagrado pela hCG, assumindo fenótipo de fase folicular.

It is well described in the literature the granulosa cells (GC) culture pattern that perpetuates human luteinizing simulating the luteal phase of the cycle. In this system, there is a reduction in the secretion of estradiol (E2) and increased synthesis of progesterone (P4) and relaxin (RLN). We aim to standardize a serum-free culture system, in order to reverse the luteinization process of GC obtained in IVF cycles, pre-luteinized by hCG, for use in in vitro maturation of preantral ovarian follicles. An experimental study was conducted with GC obtained from10 women undergoing treatment for assisted reproduction. The GC were cultured in α-MEM containing IGF-I, STI, androstenedione, PVP-40 (chemically defined medium) or TCM-199 containing FSH/serum. After 48, 96 and 144 h were analyzed: culture morphology, concentrations of E2, P4 (Chemioluminescence/Immulite), and RLN (Elisa), and ultrastructure (ElectronMicroscopy). Data were analyzed by Anova and linear mixed-effects regression (SAS version9.0). Cells cultured in α-MEM present estrogenic capacity and pattern of hormone production characteristic of the follicular phase, maintaining morphological/ultrastructural features similar that in vivo cell. In standard culture system, the CG not completes in vitro luteinization process triggered by hCG, assuming follicular phase phenotype.

Analysis of the efficiency of cervical length combined with serum relaxin for predicting premature birth / 中国医师进修杂志

Objective To determine the efficiency of cervical length by transvaginal sonography combined with serum relaxin for predicting premature birth.Methods The study enrolled 280 single births primipara.Cervical length was measured by transvaginal sonography during mid-trimester and late-trimester of pregnancy.Serum relaxin was measured during mid-trimester of pregnancy,late-trimester of pregnancy and postpartum.Sensitivity of cervical length,serum relaxin and cervical length combined with serum relaxin were applied for predicting premature birth.Results The sensitivity of cervical length and serum relaxin during mid-trimester of pregnancy for predicting premature birth were 54.43％ and 57.72％,respectively.The sensitivity of cervical length and serum relaxin during late-trimester of pregnancy for predicting premature birth was 62.74％ and 66.49％,respectively.Sensitivity of cervical length and serum relaxin during late-trimester of pregnancy for predicting preterm birth were more satisfying than those during mid-trimester of pregnancy.The sensitivity of cervical length combined with serum relaxin for predicting premature birth were 70.76％ and 71.51％,which were obviously higher than those obtained using cervical length or serum relaxin alone.Conclusion The combination of cervical length and serum relaxin can significantly improve the sensitivity of predicting premature birth,which can diagnose premature birth early and exactly.

Avaliação clínica de uma formulação de uso tópico como auxiliar na prevenção de estrias na gestação / Clinical evaluation of a topical formulation to help prevent stretch marks during pregnancy

Introdução: As estrias ocorrem pelo rápido estiramento da pele, típico da gestação. Tratamentos tópicos vêm sendo estudados para prevenir seu aparecimento. Objetivo: avaliar a eficácia preventiva de estrias de uma formulação tópica. Métodos: Avaliaram-se 75 gestantes entre 18 e 40 anos. A área tratada foi o abdome, e a área-controle, a face interna do antebraço, com e sem o produto de teste, avaliando-se: maciez, hidratação e elasticidade além de medidas biofísicas para elasticidade e hidratação. Resultados: Das 75 gestantes, 52 finalizaram o estudo; destas, 9,6% apresentaram estrias na área abdominal tratada. Houve melhora significativa em os todos parâmetros clínicos avaliados (p<0,001). Nas medidas instrumentais, houve melhora significativa da hidratação e elasticidade na área abdominal, superior à da área-controle; quanto ao antebraço, também houve melhora significativa da área tratada em relação ao controle para ambos os parâmetros avaliados (p = 0,001). Comentários e Conclusão: A associação dos ingredientes da formulação (ácido láctico e lactato de sódio em emulsão com triglicerídeos do ácido caprílico e cáprico) foi capaz de aumentar os níveis de elasticidade e hidratação, reduzindo a incidência de estrias em comparação ao relatado em literatura.

Introduction: Stretch marks occur due to the rapid stretching of the skin, which is typical in pregnancy. Several topical treatments to prevent them have been studied.Objective: To evaluate the effectiveness of a topical formulation (lactic acid and sodium lactate in an emulsion with caprylic and capric acids' triglycerides) in the prevention of stretch marks.Methods: Seventy-five pregnant women aged 18-40 were assessed. The treated area was the abdomen and the control area was the inner forearm, with and without the application of the tested product. Softness, hydration, and elasticity ­ and biophysical measurements for hydration and elasticity ­ were evaluated. Results: Of the 52 women who completed the study, 9.6% presented stretch marks in the treated abdominal area. There was a significant improvement in all clinical parameters assessed (p < 0.001). There was a significant improvement ­ compared the control area ­ in the instrumental measurements of hydration and elasticity in the abdomen. A significant improvement was also verified in the treated forearm area compared to the untreated forearm area for both parameters evaluated (p = 0.001).Conclusions: The formulation improved the skin's elasticity and hydration, reducing the striae incidence more than previously reported in the literature.

Métodos farmacológicos de indução do trabalho de parto: qual o melhor? / Pharmacological methods for induction of labor: what's the best?

A indução do parto consiste em estimular artificialmente as contrações uterinas coordenadas e efetivas antes de seu início espontâneo, levando ao desencadeamento do trabalho de parto em mulheres que ultrapassaram a 22ª semana de gravidez. A antecipação do parto pode ser necessária em diversas situações obstétricas, como gestação prolongada, diabetes, ruptura prematura das membranas e pré-eclâmpsia. Estima-se que mais de 15% de todas as gestantes apresentem alguma indicação de indução do parto. Vários métodos de indução do parto são propostos, tanto naturais como artificiais e, dentre estes, os métodos farmacológicos merecem especial destaque. Realizou-se uma revisão da literatura baseada nos melhores níveis de evidências e considerando os graus de recomendação. De acordo com a literatura, a utilização de estrogênio, propranolol, relaxina, mefepristone e hialuronidade não deve ser estimulada por não existirem evidências suficientes para a sua recomendação. O seu uso, portanto, deve ser limitado a protocolos de pesquisas. Ocitocina é um método de indução efetivo que pode ser usado em pacientes com ruptura das membranas amnióticas. Prostaglandinas (PG) e misoprostol (um éster sintético da PGE1) são efetivos para a indução do parto independentemente da integridade das membranas. Prostaglandinas devem ser administradas preferencialmente por via vaginal. Habitualmente, o misoprostol é preferido devido a questões práticas, como o baixo custo e a facilidade de administração e estocagem. Doses baixas de misoprostol devem ser utilizadas e a atualmente recomendada é de 25 g a cada 4 ou 6 horas. Tanto a via oral como a via vaginal podem ser utilizadas.

Induction of labor consists of stimulation of effective and coordinated uterine contractions before their spontaneous onset for the purpose of bring on labor in women who have surpassed the 22nd week of pregnancy. In several obstetrical situations, such as prolonged pregnancy, diabetes, premature rupture of membranes and preeclampsia, anticipation of labor and delivery may be necessary. It is estimated that more than 15% of all pregnant women eventually present any indication for induction of labor. Several natural and artificial methods for induction are proposed. Among them, pharmacological methods are the most relevant. A literature review was carried out based on the highest levels of evidence and on the grade of recommendations. According to the literature, the use of estrogens, relaxin, mifepristone and hyaluronidade should not be stimulated because there are not enough evidences for their recommendation, so their utilization should be limited to research protocols. Oxytocin is an effective method for induction of labor that may be used in patients with ruptured membranes. On the other hand, prostaglandins and misoprostol (a prostaglandin E1 analog) are effective for induction of labor independently on the membrane integrity. Vaginal administration should be preferred for prostaglandins. Misoprostol is habitually preferred due to practical questions, such as low cost and facility for storage and administration. Low doses of misoprostol should be used, and the currently recommended dose is 25 g every four or six hours. Both vaginal and oral routes of administration can be used.

Gestação e predisposição ao aparecimento de estrias: correlação com as propriedades biomecânicas da pele / Pregnancy and predisposition to striae: correlation with the skin's biomechanical properties

Introdução: O aparecimento de estrias na gestação está relacionado à ruptura de fibras colágenas e elásticas, devido à distensão da pele.As estruturas dérmicas que promovem a distensão e se rompem causando o aparecimento de estrias são também as responsáveis pelas propriedades biomecânicas da pele, como firmeza e elasticidade.A gestação parece propiciar a modificação desses parâmetros, com a finalidade de facilitar a distensão da pele, gerando, portanto, correlação entre esses parâmetros e a possibilidade de formação de estrias durante a gravidez. Objetivo: Detectar a correlação entre a ocorrência de estrias e a capacidade de aumentar a elasticidade dérmica. Métodos: Foram acompanhadas 60 gestantes visando investigar o aparecimento de estrias, bem como medir a firmeza e elasticidade da pele com o equipamento Cutometer® MPA 580.Resultados: Foi observada correlação positiva entre o aumento de elasticidade e a não ocorrência de estrias. Conclusões: Existe possível correlação entre o aparecimento de estrias e a capacidade de aumentar a elasticidade dérmica.

Introduction: Striae in pregnancy are caused by the rupture of collagen and elastic fibers, due to the distension of the skin.The dermal structures that allow the skin to expand – being responsible for the biomechanical properties of the skin such as firmness and elasticity – when ruptured, cause striae. Since pregnancy seems to change these properties in order to facilitate skin distension, there is a correlation between those parameters and the occurrence of striae during pregnancy. Objective: To investigate the correlation between the occurrence of striae and the skin's capacity to increase its elasticity. Methods: Skin firmness and elasticity was measured with a Cutometer MPA 580® device in order to investigate the occurrence of striae in 60 pregnant women. Results: A positive correlation between increased elasticity and the absence of striae was observed. Conclusions: There is a possible correlation between the occurrence of striae and the skin's capacity to increase dermal elasticity.

Relationship between pelvic floor dysfunction and serum relaxin H2 and expression of vaginal wall relaxin receptor LGR7 mRBA in late pregnant women / 上海交通大学学报（医学版）

Objective To investigate the relationship between pelvic floor dysfunction and serum relaxin H2 and expression of vaginal wall relaxin receptor LGR7 mRNA in late pregnant women. Methods Before the beginning of delivery,all women were evaluated by pelvic organ prolapse quantitation(POP-Q)scoring.Twelve women with stress urinary incontinence(SUI)and stage II prolapse of anterior vaginal wall were selected as patient group,and another 24 women without SUI and prolapse of pelvic floor were served as control group.Serum relaxin H2 was determined by ELISA.Vaginal wall tissues were taken after vaginal delivery,and the expression of relaxin receptor LGR7 mRNA was detected by RT-PCR.Results The serum level of relaxin H2 and expression of LGR7 mRNA of vaginal tissues in patient group were significantly higher than those in control group(P<0.01,P<0.05). Conclusion The increased level of serum relaxin and expression of vaginal wall relaxin receptor may correlate with the pelvic floor dysfunction in late pregnant women.

Effect of Relaxin Expressing Adenovirus for Rat Skin Flap Viability

PURPOSE: Of various effects of relaxin, we assumed that anti-fibrotic effects, neovascularization effects and vasodilatation effects of relaxin might enhance the survival rate of skin flap. In the current study, we used adenovirus expressing relaxin genes to examine whether these genes could enhance the survival rate of a skin flap. METHODS: A total of 30 Sprangue-Dawley rats were divided into three groups: RLX group (10; relaxin virus injected group), CTR group (10; no gene coded virus injection group), and PBS group (10; PBS injected group). Each group was intradermally injected with the virus (107 PFU) and PBS 48 hours before and immediately before the flap elevation. A distally based flap 3 x 9 cm in size was elevated on the dorsal aspect of each rat. Following this, a flap was placed in the original location and then sutured using a #4-0 Nylon. A surviving area of the flap was measured and then compared on postoperative days 3, 7 and 10. Using a laser Doppler, the amount of blood flow was measured. On postoperative day 10, tissues were harvested for histologic examination and the number of blood vessels was counted. RESULTS: There was a significant increase in the area of the flap survival in the RLX group on postoperative days 3 and 7. The Doppler measurement also showed significantly increased blood flow immediately after the operation and on postoperative days 7 and 10. The number of blood vessels was significantly greater in the RLX group in the tissue harvested on postoperative day 10. The VEGF concentration was significantly higher in the RLX group than others in the tissues harvested on postoperative day 10. CONCLUSION: Following an analysis of the effects of relaxin-secreting adenovirus on the survival of a flap, the surviving area of the flap and the blood flow also increased. A histopathology also showed an increase in the number of blood vessels and the concentration of VEGF.

Expression and function of G-protein-coupled receptorsin the male reproductive tract

This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.

Esta revisão enfatiza a expressão e a função dos receptores muscarínicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressão dos receptores muscarínicos e adrenoceptores α1 em compartimentos específicos de dúctulos eferentes, epidídimo, ductos deferentes, vesícula seminal e próstata de várias espécies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do músculo liso, incluindo efeitos na fertilidade masculina. Além disso, a ativação dos receptores muscarínicos leva à transativação do receptor para o fator crescimento epidermal e proliferação das células de Sertoli. Os receptores para relaxina estão presentes no testículo, RXFP1 nas espermátides alongadas e células de Sertoli de rato e RXFP2 nas células de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogênico. A localização de ambos os receptores na porção apical das células epiteliais e no músculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.