Search Results (12)

Background/Objectives: Intermittent parathyroid hormone (PTH) administration increases bone quantity. Existing animal studies have revealed improvements in tissue healing around implants after PTH administration. It is still unclear whether PTH has a beneficial short-term effect on the early healing of bone and soft tissue around implants in individuals with osteoporosis. The current study aims to examine whether short-term intermittent PTH administration accelerates and improves early tissue healing around implants in ovariectomized rats. Methods: Ovariectomized rats received implants at the healed sites of extracted maxillary first molar sockets 12 weeks after the ovariectomy surgery. A daily dose of PTH was subcutaneously administered in the test group, whereas saline was administered for the control group. Long bones and maxillae were harvested 1 week after PTH administration. The following criteria were assessed: quantity and quality of long bones and peri-implant bone, bone healing around the implants, and soft tissue healing. Results: PTH significantly increased the bone parameters of long bones. Moreover, the bone volume around the implant increased significantly compared to controls. Improved bone quality was indicated through PTH administration by increased numbers of osteoblasts and osteoclasts, as well as decreased quantities of sclerostin + osteocytes. Furthermore, PTH administration significantly improved soft tissue healing, promoted collagen production and angiogenesis, and increased the numbers of macrophages in the connective tissue around the implants. Conclusions: Short-term intermittent PTH administration significantly accelerates soft tissue healing, which could lead to enhanced early osseous healing and bone formation around implants. Thus, Intermittent PTH administration might be considered as an available treatment modality for dental implants in osteoporosis patients. Full article

Background: Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone mass recovery in ovariectomized rats and its underlying mechanisms remains unclear. In this study, trehalose was administered to ovariectomized rats to evaluate its therapeutic potential for osteoporosis following ovariectomy. Methods: Micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) and immunohistochemical staining techniques were utilized to evaluate the impact of trehalose on osteoporosis induced by ovariectomy (OVX) in mice, both in imaging and histological dimensions. Furthermore, the influence of trehalose on osteoblastogenesis and functional activity was quantified through Alizarin Red S (ARS) staining and immunoblotting assays. Results: Trehalose effectively mitigated bone loss, elevated autophagy and suppressed pyroptosis in ovariectomized rats. Furthermore, 3-methyladenine diminished the protective effects of trehalose, particularly in promoting autophagy and inhibiting pyroptosis. Conclusions: Trehalose demonstrates significant potential in treating osteoporosis by suppressing NLRP3 inflammasome-driven pyroptosis, primarily through autophagy promotion. This suggests that trehalose could be a promising, safer alternative treatment for osteoporosis. Full article

Owner complaints of estrus-related behavior in mares are a common cause of referral for laparoscopic ovariectomy. Granulosa cell tumors are a common neoplastic condition affecting the equine ovary, causing behavioral changes at rest and reduced performance. The reported success rate of ovariectomy in treating behavioral disorders is 64–86%. The aim of this study was to retrospectively evaluate the long-term follow-up of laparoscopic ovariectomy in mares in our case series, focusing on the owner’s perspective of the behavior of the mares after surgery. In addition, the histopathological features of the removed ovaries were investigated. The clinical records of mares that underwent laparoscopic ovariectomy between 2015 and 2022 were retrospectively reviewed. Owners complaining of poor behavior were interviewed about the main behavioral problem leading to referral and its eventual resolution after surgery. Eleven mares were included. The most common complaints were increased sensitivity on both flanks (10/11, 91%) and general riding problems (9/11, 82%). In 5/11 cases (45%), both ovaries were removed by laparoscopic ovariectomy. Histopathologic findings consistent with GCT/GTCT were found in five out of six examined ovaries (five granulosa theca cell tumors, GTCT). According to owner interviews, the scores assigned to each behavior improved significantly after surgery, regardless of histological findings. Although many factors can influence the behavior of horses, granulosa cell tumors (GCTs) proved to be a common cause and, as reported by the owners, ovariectomy resulted in improvement or complete resolution of the abnormal behavior. Full article

Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as ovarian function decreases. Hormone-replacement therapy is mainly used to treat menopause; however, its long-term use is accompanied by side effects such as breast cancer and endometriosis. To identify the effect of a complex extract of Polygonatum sibiricum (PS) and Nelumbinis semen (NS) on improving menopause without side effects, an ovariectomized rat model was established to analyze several menopause symptoms. Compared to single extracts, the complex extract restored vaginal epithelial cell thickness and decreased serotonin concentration by increasing the estrogen receptors ERα (ESR1) and ERβ (ESR2), depending on the ratio. Although the complex extract exerted a lower weight-loss effect than the single extracts, improved blood-lipid metabolism was observed after increasing high-density lipoprotein cholesterol levels and decreasing low-density lipoprotein cholesterol and triglyceride levels, and ovariectomy-induced osteoporosis was alleviated by suppressing osteoclast production. Thus, by increasing only ERβ expression without regulating ERα expression in the uterus, the complex extract of PS and NS may be a natural treatment for improving menopause symptoms without side effects, such as endometriosis. Full article

Osteoporosis and age-related bone loss increase bone fracture risk and impair bone healing. The need for identifying new factors to prevent or treat bone loss is critical. Previously, we reported that young MRL/MpJ mice have superior bone microarchitecture and biomechanical properties as compared to wild-type (WT) mice. In this study, MRL/MpJ mice were tested for resistance to age-related and long-term ovariectomy-induced bone loss to uncover potential beneficial factors for bone regeneration and repair. Bone tissues collected from 14-month-old MRL/MpJ and C57BL/6J (WT) mice were analyzed using micro-CT, histology, and immunohistochemistry, and serum protein markers were characterized using ELISAs or multiplex assays. Furthermore, 4-month-old MRL/MpJ and WT mice were subjected to ovariectomy (OV) or sham surgery and bone loss was monitored continuously using micro-CT at 1, 2, 4, and 6 months (M) after surgery with histology and immunohistochemistry performed at 6 M post-surgery. Sera were collected for biomarker detection using ELISA and multiplex assays at 6 M after surgery. Our results indicated that MRL/MpJ mice maintained better bone microarchitecture and higher bone mass than WT mice during aging and long-term ovariectomy. This resistance of bone loss observed in MRL/MpJ mice correlated with the maintenance of higher OSX⁺ osteoprogenitor cell pools, higher activation of the pSMAD5 signaling pathway, more PCNA⁺ cells, and a lower number of osteoclasts. Systemically, lower serum RANKL and DKK1 with higher serum IGF1 and OPG in MRL/MpJ mice relative to WT mice may also contribute to the maintenance of higher bone microarchitecture during aging and less severe bone loss after long-term ovariectomy. These findings may be used to develop therapeutic approaches to maintain bone mass and improve bone regeneration and repair due to injury, disease, and aging. Full article

Historically, a high level of estrogen in women is regarded as the signature for a longer lifespan than men. Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Ovariectomy brings on numerous complications such as early menopause, heart disease, and osteoporosis. Thus, ovariectomy impacts the long-term health and lifespan of women. However, the level of estrogen at different life stages should be managed differently. Life quality can be measured in many ways, but mainly it relates to how an individual is doing in terms of being healthy, comfortable, and able to participate in or enjoy life experiences. First of all, ovariectomy not only reduces the level of estrogen but also destroys the reproductive metabolism and potentially other metabolism functions; it may also reduce the lifespan because of the overall impact, not necessary due to the low level of estrogen. Secondly, according to the principal law of the lifespan (PLOSP), the impacts of ovariectomy at different life stages will be different. The objective of this article is to provide readers with a new view of the research on estrogen. Based on the PLOSP, we recapture the estrogen levels at different life stages and explore potential alternative approaches to the manipulation of the levels of estrogen based on the biological features of the difference life stages. Thus, a low level of estrogen in the early life stage may make a woman live longer than a woman with a normal level of estrogen. However, a low estrogen level does not equal ovariectomy. Here, we explain the different impacts of the estrogen levels during different life stages; the effects on the lifespan of the manipulation of estrogen levels at different life stages; and the differences among the estrogen levels, ovariectomy effects, life stages, and lifespan. The personalized manipulation of estrogen levels and relevant growth factors according to the characterization of the life stages may be able to extend the heathy lifespan of women. Full article

Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 μm and 86.9 μm) at the peri-implant area, compared to control (43.2 μm and 39.2 μm), enoxaparin (39.6 μm and 24 μm), and fondaparinux (36.2 μm and 32.7 μm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation. Full article

Background: Ovarian masses in pediatric populations are the most common abdominal masses in young girls. In neonates, the majority of masses are benign while in children and teen-agers the risk of malignancy exists. The aim of this study is to perform a 25-year experience retrospective analysis of clinical and therapeutic aspects of ovarian tumors in girls, in order to show how the development of minimally invasive technology has changed the management of this pathology. Methods: The records of patients under the age of 18 who were operated in three pediatric surgical units due to ovarian mass, in the last 25 years, were reviewed retrospectively. The study group comprised 147 patients operated between 1996 and 2021 with a diagnosis of ovarian masses. Data involved were demographical, surgical, follow-up and final diagnosis. We analyzed the type of surgical technique, intra-operative data (operative time, the use of different technologies), complications, length of stay and long-term follow-up. Based on these data, we assessed how the surgical approach to ovarian masses has changed in the last 25 years in newborns and young girls. Results: The patients ages ranged between 7 days and 15 years (median, 59 days). All the procedures were completed in laparoscopy or robotics without conversion in open surgery. One-hundred and eleven patients were neonates; they all had follicular cysts and they were all managed in laparoscopy using 1 or 3 trocars. In 80/111 patients (72%), a small part of ovarian parenchyma was saved; in 31/111 patients (28%), in which the ovarian parenchyma was not available, an ovariectomy was performed. Patients in which we saved a small part of ovary, at long term follow-up (minimum follow-up of 12 years) (29/80, 36%), developed a normal ovary at US control. Thirty-six were older patients. They had a histological diagnosis of benign (30) or malign (6) tumors. All the patients (8/36) with a pre-operative suspicion of ovarian malignancy received an ovariectomy and an adnexectomy using sealing devices. In the last 10 years in all the children, except neonates, we adopted sealing devices and, in the last 4 years, in 20 cases, we always adopted ICG fluorescence technology to check ovarian vascularization in case of torsion or to check lympho-nodes condition in case of malignancy. Conclusions: In neonatal ovarian cysts, surgical management remained unchanged and an ovarian sparing procedure is always indicated and the long-term follow-ups confirm this hypothesis. The principal innovation in this age period is the use of ICG fluorescence technology to check ovarian vascularization in case of torsion. In teenagers, the decision-making strategy is based on the tumoral markers and on the morphological aspects of the mass. Robotics cystectomy or ovariectomy now-days represents the safer and faster way to perform this. Sealing devices are essential tools for dissection and resection to avoid bleeding. ICG fluorescence technology in all ages is fundamental to check ovary vascularization after detorsion or to check lympho-node status in case of malignancy. All the suspected lesions have to be removed with an endo-bag. Full article

Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1–34 and 107–139); mcPTHrP 1–34+107–139 using a minicircle vector. We also transfected mcPTHrP 1–34+107–139 into human mesenchymal stem cells (MSCs) and generated Thru 1–34+107–139-producing engineered MSCs (eMSCs) as an alternative delivery system. Osteoporosis was induced in 12-week-old C57BL/6 female mice via ovariectomy. The ovariectomized (OVX) mice were then treated with the two systems; (1) mcPTHrP 1–34+107–139 was intravenously administered three times (once per week); (2) eMSCs were intraperitoneally administered twice (on weeks four and six). Compared with the control OVX mice, the mcPTHrP 1–34+107–139-treated group showed better trabecular bone structure quality, increased bone formation, and decreased bone resorption. Similar results were observed in the eMSCs-treated OVX mice. Altogether, these results provide experimental evidence to support the potential of delivering PTHrP 1–34+107–139 using the minicircle technology for the treatment of osteoporosis. Full article

The purpose of this study was to explore the antidepressant-like effects of vitamin D₃ at different doses (1.0, 2.5, and 5.0 mg/kg sc) on a model of depression produced by chronic unpredictable mild stress (CUMS) for 28 days in long-term (3 months) ovariectomized (OVX) adult rats. Sucrose preference (SPT), forced swimming (FST) and open-field (OFT) tests were conducted to examine the depression-like state. Serum corticosterone/adrenocorticotrophic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3/NT-4 expressions by ELISA kits and/or western blotting were determined to assess the possible mechanisms of the vitamin D₃ effects on the depression-like profile in long-term OVX rats subjected to CUMS. The results showed that vitamin D₃ (5.0 mg/kg), as well as fluoxetine treatment, considerably reversed the depression-like state in the SPT and FST, decreased serum corticosterone/ACTH levels, and increased BDNF and NT-3/NT-4 levels in the hippocampus of long-term OVX rats compared to OVX rats with CUMS (p < 0.05). Thus, a high dose of vitamin D₃ (5.0 mg/kg sc) could improve the depression-like profile in long-term OVX adult female rats subjected to the CUMS procedure, which might be mediated by the regulation of BDNF and the NT-3/NT-4 signaling pathways in the hippocampus, as well as the corticosterone/ACTH levels of the blood serum. Full article

Rice porridge containing Allium fistulosum (Welsh onion) root water extract (RAFR) has anti-inflammatory bioactive compounds. We examined whether the long-term administration of rice porridge with RAFR would prevent or delay the progression of osteoarthritis and menopausal symptoms in estrogen-deficient animals by ovariectomy. The rats consumed 40% fat energy diets containing 250 mg RAFR (rice: Allium fistulosum root = 13:1)/kg body weight (bw) (OVX-OA-RAFR-Low), 750 mg RAFR/kg bw (OVX-OA-RAFR-High) and 750 mg starch and protein/kg bw(OVX), respectively. After consuming the assigned diets for eight weeks, monoiodoacetate (OVX-OA) or saline (OVX) were injected into the knee joints of the rats for an additional three weeks. Sham rats were administered saline injections (normal-control). OVX-OA-RAFR improved oral glucose tolerance and also protected against decreases in bone mineral density and lean body mass in the legs and increases in fat mass in the abdomen, compared to the OVX and OVX-OA. OVX-OA-RAFR improved swelling and limping scores, normalized weight distribution between the osteoarthritic and normal limbs, and increased maximum running speeds compared to the OVX-OA. The OVX-OA deteriorated the articular cartilage by reducing the articular matrix and bone loss in the knee joint and it prevented knee joint deterioration when compared to the OVX. The improvement in osteoarthritis symptoms in OVX-OA-RAFR decreased the mRNA expression of matrix metallo-proteinase-1 and matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1β and interleukin-6 in the articular cartilage compared to OVX-OA rats. In conclusions, RAFR is effective in treating osteoarthritis symptoms and it may be used for a therapeutic agent in osteoarthritis-induced menopausal women. Full article

The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E₂) on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days) on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX) rats and OVX rats treated with 17β-E₂ (0.5 µg/rat SC, once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light/dark test (LDT), and locomotor and grooming activities were tested in the open field test (OFT). Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E₂ produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency. Full article