skeletal disease
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Gut Pathogens ◽  
2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Jana Schreier ◽  
Daniela Karasova ◽  
Magdalena Crhanova ◽  
Ivan Rychlik ◽  
Silke Rautenschlein ◽  
...  

Abstract Background Enterococcus cecorum (EC) is one of the main reasons for skeletal disease in meat type chickens. Intervention strategies are still rare and focus mainly on early antibiotic treatment of the disease, although there are no data available concerning the effectivity of this procedure. The present study aimed to investigate the effectivity of early lincomycin-spectinomycin treatment during the first week of life after EC-infection. Furthermore, the impact of lincomycin-spectinomycin treatment and EC infection on the development of cecal microbiota was investigated. Methods A total of 383 day-old broiler chicks were randomly assigned to four groups (non-infected and non-treated, non-infected and treated, EC-infected and non-treated, and EC-infected and treated). The EC-infected groups were inoculated orally with an EC suspension at the day of arrival and at study day 3. The treatment groups were treated with lincomycin-spectinomycin via the drinking water for six consecutive days, starting two hours after the first inoculation. Necropsy of 20 chickens per group was performed at study days 7, 14, 21, and 42. Bacteriological examination via culture and real-time PCR was performed to detect EC in different extraintestinal organs. Cecal samples of nine chickens per group and necropsy day were analyzed to characterize the composition of the cecal microbiota. Results No clinical signs or pathologic lesions were found at necropsy, and EC was not detected in extraintestinal organs of the EC-infected and treated birds. Lincomycin-spectinomycin promoted the growth of the bacterial genus Escherichia/Shigella and reduced the amount of potentially beneficial Lactobacillus spp. in the ceca regardless of EC-infection. Unexpectedly, the highest abundances of the genus Enterococcus were found directly after ending antibiotic treatment in both treatment groups, suggesting the growth of resistant enterococcal species. EC was not detected among the most abundant members of the genus Enterococcus. Oral EC-infection at the first day of life did not influence the development of cecal microbiota in the present study. Conclusions Lincomycin-spectinomycin treatment during the first week of life can prevent the EC-associated disease in broiler type chickens and has a direct impact on the development of the cecal microbiota. The low abundance of EC in the ceca of infected chickens underlines the pathogenic nature of the disease-causing EC strains. Further research on alternative prevention and intervention strategies is needed with regard to current efforts on reducing the use of antibiotics in livestock animals.


2021 ◽  
Vol 12 (4) ◽  
pp. 2345-2349
Author(s):  
Mohsin Aijaz Soomro ◽  
Raheel Akbar Baloch ◽  
Najeeb ur Rehman ◽  
Niaz Hussain Keerio ◽  
Muhammad Faraz Jokhio ◽  
...  

Osteoporosis is a skeletal disease that is characterized by low bone mineral density. It also disrupts the microarchitectural of the bone. In leads to increased bone fragility and risk of fractures. Even while it occurs in persons of various ages and ethnicities (including Caucasians and whites), it is more common among Caucasians (whites), elderly people, and women. Osteoporosis is becoming a global epidemic as the world's population ages and lives longer. Osteoporosis affects an estimated 200 million individuals worldwide. It affects a 3rd of women and one in every 12 men. This increases morbidity as well as mortality due to several complications. Moreover, It also reduces the patient's quality of life, lengthens their life expectancy when they are disabled, and places a heavy financial load on the health insurance systems of countries that are responsible for their care. Thus, it is essential to improve diagnostic methods and to introduce early intervention to prevent this disease. Lifestyle modification is an important recommendation for the population at risk. There are several pharmacological interventions that could be taken to prevent osteoporosis as vitamin D and calcium supplements and to treat osteoporosis as bisphosphonates and anabolic drugs. The most important step in the treatment is tailored to the individual patients and to optimize the treatment according to each case individually. Therefore, increasing doctor awareness, which promotes improved awareness among the general public, will be useful in averting this epidemic. 


2021 ◽  
Vol 48 (3) ◽  
pp. 30-33
Author(s):  
H. Valkov ◽  
M. Kovacheva-Slavova ◽  
I. Lyutakov ◽  
T. Angelov ◽  
P. Getsov ◽  
...  

Abstract Diffuse idiopathic skeletal hyperostosis (DISH) is a common but underdiagnosed systemic skeletal disease. It is characterized by calcifications affecting mainly the spinal anterior longitudinal ligament. In the majority of cases, the patients are asymptomatic, but cervical osteophytes can sometimes cause hoarseness, dysphagia (DISHphagia) and even dyspnea. Case description: A 61-year-old man was admitted to our department with complaints of difficulty in swallowing and weight loss. Dysphagia had been increasing gradually for nine months. Barium swallow esophagram revealed asymmetric swallowing with expansion above the upper esophageal sphincter without other abnormalities. The extension was confirmed by esophago-gastro-duodenoscopy (EGD). Furthermore, CT scan of the thorax clearly demonstrated degenerative changes of the cervical and thoracic region, extensive ossification of the anterior longitudinal ligament, and osteophytes from C2-C7 with a forward displacement of the esophagus by 14 mm. The so-called “wax dripping down the candle” phenomenon was as well observed. Conclusion: DISH is a systematic, musculo-skeletal disease of older adults with unknown etiology. Dysphagia is the most common symptom of the disease and might be caused by osteophytes of the cervical region. We presented a case of DISH with a rare localization of the osteophytes in the cervical region C2-C7. Due to the increasing incidence of the Forestier’s syndrome and its associated “DISHphagia”, the gastroenterologist should increase the awareness of this underestimated disease and improve the diagnostic approach.


2021 ◽  
Vol 22 (19) ◽  
pp. 10336
Author(s):  
Luca Dalle Carbonare ◽  
Franco Antoniazzi ◽  
Alberto Gandini ◽  
Silvia Orsi ◽  
Jessica Bertacco ◽  
...  

Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the RUNX2 gene have been identified in most CCD patients. Transcription factor RUNX2, the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of RUNX2 mutations in CCD patients, we investigated RUNX2 gene expression and the osteogenic potential of two CCD patients’ cells. In addition, with the aim to better understand how RUNX2 mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, RUNX2 mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of RUNX2 mutations in CCD patients and suggests that an in-depth analysis of the RUNX2-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects.


2021 ◽  
Vol 12 ◽  
Author(s):  
Liangwei Mei ◽  
Yi Zheng ◽  
Teng Ma ◽  
Bing Xia ◽  
Xue Gao ◽  
...  

Inflammatory osteolysis is a pathological skeletal disease associated with not only the production of inflammatory cytokines but also local oxidative status. Excessive reactive oxygen species (ROS) promote bone resorption by osteoclasts and induce the apoptosis of osteoblasts. In consideration of the lack of effective preventive or treatments options against osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. In our study, we found that a novel antioxidant compound, JSH-23, plays a role in restoring bone homeostasis by scavenging intracellular ROS during both osteoclastogenesis and osteoblastogenesis. Mechanically, JSH-23 suppressed RANKL-induced osteoclastogenesis, bone resorption and the expression of specific genes (including NFATc1, c-Fos, TRAP, CTSK and DC-STAMP) via inhibition of the NF-κB signaling pathway. Meanwhile, JSH-23 suppressed RANKL-induced ROS generation via the TRAF6/Rac1/NOX1 pathway and the enhanced expression of Nrf2/HO-1. In addition, JSH-23 attenuated H2O2-induced apoptosis and mineralization reduction in osteoblasts by reducing ROS production and enhancing Nrf2/HO-1 expression. Our in vivo results further revealed that JSH-23 exerts its protective effects on bone mass through its antioxidant activity. In conclusion, our results show that the application of JSH-23 might be a novel and plausible strategy for the treatment of osteolysis-related disease.


2021 ◽  
Vol 22 (17) ◽  
pp. 9590
Author(s):  
Anna Nasulewicz-Goldeman ◽  
Waldemar Goldeman ◽  
Anna Nikodem ◽  
Marcin Nowak ◽  
Diana Papiernik ◽  
...  

Osteoporosis is a skeletal disease associated with excessive bone turnover. Among the compounds with antiresorptive activity, nitrogen-containing bisphosphonates play the most important role in antiosteoporotic treatment. In previous studies, we obtained two aminomethylidenebisphosphonates—benzene-1,4-bis[aminomethylidene(bisphosphonic)] (WG12399C) acid and naphthalene-1,5-bis[aminomethylidene(bisphosphonic)] (WG12592A) acid—which showed a significant antiproliferative activity toward J774E macrophages, a model of osteoclast precursors. The aim of these studies was to evaluate the antiresorptive activity of these aminobisphosphonates in ovariectomized (OVX) Balb/c mice. The influence of WG12399C and WG12592A administration on bone microstructure and bone strength was studied. Intravenous injections of WG12399C and WG12592A bisphosphonates remarkably prevented OVX-induced bone loss; for example, they sustained bone mineral density at control levels and restored other bone parameters such as trabecular separation. This was accompanied by a remarkable reduction in the number of TRAP-positive cells in bone tissue. However, a significant improvement in the quality of bone structure did not correlate with a parallel increase in bone strength. In ex vivo studies, WG12399C and WG12592A remarkably bisphosphonates reduced osteoclastogenesis and partially inhibited the resorptive activity of mature osteoclasts. Our results show interesting biological activity of two aminobisphosphonates, which may be of interest in the context of antiresorptive therapy.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 930
Author(s):  
Min-Yu Tu ◽  
Kuei-Yang Han ◽  
Ying-Wei Lan ◽  
Ku-Yi Chang ◽  
Cheng-Wei Lai ◽  
...  

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (−509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (−509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (−509 C/T) genotype in all subjects and TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (−509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.


Author(s):  
Jonathan J Rios ◽  
Kristin Denton ◽  
Hao Yu ◽  
Kandamurugu Manickam ◽  
Shannon Garner ◽  
...  

Embryonic formation and patterning of the vertebrate spinal column requires coordination of many molecular cues. After birth, the integrity of the spine is impacted by developmental abnormalities of the skeletal, muscular, and nervous systems, which may result in deformities such as kyphosis and scoliosis. We sought to identify novel genetic mouse models of severe spine deformity by implementing in vivo skeletal radiography as part of a high-throughput saturation mutagenesis screen. We report selected examples of genetic mouse models following radiographic screening of 54,497 mice from 1,275 pedigrees. An estimated 30.44% of autosomal genes harbored predicted damaging alleles examined twice or more in the homozygous state. Of the 1,275 pedigrees screened, 7.4% presented with severe spine deformity developing in multiple mice, and of these, meiotic mapping implicated ENU alleles in 21% of pedigrees. Our study provides proof-of-concept that saturation mutagenesis is capable of discovering novel mouse models of human disease, including conditions with skeletal, neural, and neuromuscular pathologies. Furthermore, we report a mouse model of skeletal disease, including severe spine deformity, caused by recessive mutation in Scube3. By integrating results with a human clinical exome database, we identified a patient with undiagnosed skeletal disease who harbored recessive mutations in SCUBE3, and we demonstrated that disease-associated mutations are associated with reduced trans-activation of Smad signaling in vitro. All radiographic results and mouse models are made publicly available through the Mutagenetix online database with the goal of advancing understanding of spine development and discovering novel mouse models of human disease.


2021 ◽  
pp. 56-69
Author(s):  
Derya Köseoğlu ◽  
Gülnur Take ◽  
Banu Aktaş Yılmaz ◽  
Erdal Kan ◽  
Nuri Çakır

Background: Osteoporosis is a metabolic skeletal disease with low bone mass and bone microarchitectural disorganization. Thiazolidinediones (TZD) increase insulin sensitivity through activation of peroxisome proliferator-activated receptor gamma (PPARγ). One of the most important side effects of this drugs is its effects on bone, especially in postmenopausal women. The purpose of this study was to evaluate the effect of diabetes mellitus (DM), insulin, and TZDs on bone in postmenopausal Wistar rats. Methods: Sixteen postmenopausal Wistar rats were divided into four groups: (i) control group, (ii) Streptozotocin-induced DM group without treatment, (iii) Streptozotocin-induced DM group with insulin therapy, and (iv) Streptozotocin-induced DM group receiving rosiglitazone. Pictures of the obtained samples were taken under computer-equipped photo-light microscope, and bone tissue ratios were calculated in an area of 1 mm2. In this area, trabecular thicknesses were measured from six randomly selected regions. In addition, femoral neck regions were determined by measuring the farthest distance. Results: Compared to the control group, trabecular thicknesses were decreased in the uncontrolled DM and rosiglitazone groups. In the rosiglitazone-treated group, trabecular thickness was decreased compared to the uncontrolled DM group. The histological examination of the bones showed that uncontrolled DM and rosiglitazone treatment negatively affected the osteoblast and osteocyte activity. Insulin-treated group had a similar histologic examination compared to the control group. Conclusion: Our study showed that DM had unfavorable effects on bones, and rosiglitazone further exerts this effect. However, the negative effect of DM may be neutralized with the use of insulin. Keywords: diabetes mellitus, bone, osteoporosis, bone histomorphometry, rosiglitazone, insulin, thiazolidinediones


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