RESUMO
A total of 882 pigs (PIC TR4â ×â [Fast LWâ ×â PIC L02]; initially 33.2â ±â 0.31 kg) were used in a 112-d study to evaluate the effects of different bones and analytical methods on the assessment of bone mineralization response to changes in dietary P, phytase, and vitamin D in growing pigs. Pens of pigs (20 pigs per pen) were randomized to one of five dietary treatments with nine pens per treatment. Dietary treatments were designed to create differences in bone mineralization and included: 1) P at 80% of NRC (2012) standardized total tract digestible (STTD) P requirement, 2) NRC STTD P with no phytase, 3) NRC STTD P with phytase providing an assumed release of 0.14% STTD P from 2,000 FYT/kg, 4) high STTD P (128% of the NRC P) using monocalcium phosphate and phytase, and 5) diet 4 with additional vitamin D3 from 25(OH)D3. On day 112, one pig per pen was euthanized for bone, blood, and urine analysis. Additionally, 11 pigs identified as having poor body condition which indicated a history of low feed intake (unhealthy) were sampled. There were no differences between treatments for final body weight, average daily gain, average daily feed intake, gain to feed, or bone ash measurements (treatmentâ ×â bone interaction) regardless of bone ash method. The response to treatment for bone density and bone mineral content was dependent upon the bone sampled (density interaction, Pâ =â 0.053; mineral interaction, Pâ =â 0.078). For 10th rib bone density, pigs fed high levels of P had increased (Pâ <â 0.05) bone density compared with pigs fed NRC levels with phytase, with pigs fed deficient P, NRC levels of P with no phytase, and high STTD P with extra 25(OH)D3 intermediate, with no differences for metacarpals, fibulas, or 2nd ribs. Pigs fed extra vitamin D from 25(OH)D3 had increased (Pâ <â 0.05) 10th rib bone mineral content compared with pigs fed deficient P and NRC levels of P with phytase, with pigs fed industry P and vitamin D, and NRC P with monocalcium intermediate. Healthy pigs had greater (Pâ <â 0.05) serum Ca, P, vitamin D concentrations, and defatted bone ash than those unhealthy, with no difference between the two health statuses for non-defatted bone ash. In summary, differences between bone ash procedures were more apparent than differences between diets. Differences in bone density and mineral content in response to dietary P and vitamin D were most apparent with 10th ribs.
Lameness is defined as impaired movement or deviation from normal gait. The evaluation of bone mineralization can be an important component of a diagnostic investigation of lameness. Lameness in growing pigs can cause an increase in morbidity and mortality, which leads to economic losses and animal welfare concerns for producers. Calcium and P are the primary minerals in skeletal tissue and their deficiency is considered to be one of the causes of lameness. To evaluate bone mineralization, it is important to know the differences between methodologies used to determine bone ash and the expected differences between the bones analyzed. Furthermore, there has been limited data comparing bone mineralization and serum Ca and P concentrations between healthy pigs and those exhibiting clinical signs of illness (unhealthy). By removing the lipid in the bone (defatting) before the bone is ashed, variation across bones is decreased compared with not removing lipid before ashing (non-defatted). The reduction in variation across bones allows for more differences to be detected among dietary treatments and health statuses of pigs. The 10th rib is more sensitive to detect dietary differences using bone density than metacarpals, fibulas, and 2nd ribs. When comparing healthy vs. unhealthy pigs exhibiting clinical signs of illness, healthy pigs have increased defatted percentage bone ash and serum Ca, P, and vitamin D.
Assuntos
6-Fitase , Ração Animal , Calcificação Fisiológica , Dieta , Fósforo na Dieta , Vitamina D , Animais , 6-Fitase/administração & dosagem , 6-Fitase/farmacologia , 6-Fitase/metabolismo , Ração Animal/análise , Dieta/veterinária , Suínos/fisiologia , Suínos/crescimento & desenvolvimento , Calcificação Fisiológica/efeitos dos fármacos , Vitamina D/administração & dosagem , Vitamina D/sangue , Fósforo na Dieta/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Animal , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Suplementos Nutricionais/análise , Densidade Óssea/efeitos dos fármacos , Fósforo/metabolismo , Fósforo/sangue , Distribuição AleatóriaRESUMO
Octacalcium phosphate (OCP, Ca8H2(PO4)6·5H2O) is known to be a possible precursor of biological hydroxyapatite formation of organic bone tissue. OCP has higher biocompatibility and osseointegration rate compared to other calcium phosphates. In this work, the synthesis of low-temperature calcium phosphate compounds and substituted forms of those at physiological temperatures is shown. Strontium is used to improve bioactive properties of the material. Strontium was inserted into the OCP structure by ionic substitution in solutions. The processes of phase formation of low-temperature OCP with theoretical substitution of strontium for calcium up to 50 at.% in conditions close to physiological, i.e., temperature 35-37 °C and normal pressure, were described. The effect of strontium substitution range on changes in the crystal lattice of materials, the microstructural features, surface morphology and biological properties in vitro has been established. The results of the study indicate the effectiveness of using strontium in OCP for improving biocompatibility of OCP based composite materials intended for bone repair.
Assuntos
Materiais Biocompatíveis/farmacologia , Regeneração Óssea , Osso e Ossos/citologia , Fosfatos de Cálcio/síntese química , Fosfatos de Cálcio/farmacologia , Mesoderma/citologia , Animais , Materiais Biocompatíveis/síntese química , Osso e Ossos/efeitos dos fármacos , Durapatita/química , Técnicas In Vitro , Mesoderma/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3H , Espécies Reativas de Oxigênio/metabolismo , Estrôncio/química , Engenharia TecidualRESUMO
BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Cálcio/administração & dosagem , Suplementos Nutricionais , Guias de Prática Clínica como Assunto/normas , Recomendações Nutricionais , Vitamina D/administração & dosagem , Adulto , Osso e Ossos/fisiopatologia , Cálcio/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Medicina Baseada em Evidências/normas , Feminino , Nível de Saúde , Disparidades em Assistência à Saúde/normas , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Osteoporose/prevenção & controle , Vitamina D/efeitos adversosRESUMO
Bone tissue engineering compasses the use of mesenchymal stem cells (MSCs) along with engineered biomaterial construct to augment bone regeneration. Till now, MSCs were isolated from various sources and used in cellular constructs. For the first time, in this study, MSCs were isolated from human Ovarian Follicular Fluid (OFF) and characterized by CD 44+ and CD 105+ markers via confocal microscopy and flow cytometry. Additionally, MSCs stemness, proliferation and colony-forming unit ability, multi-lineage differentiation potential were also studied. To test its suitability for bone tissue engineering applications, we grew the MSCs with the conditioned medium obtained from biocomposite scaffold by fusing a natural polymer, Chitosan (CS) and a synthetic polymer, Polycaprolactone (PCL) and the scaffold were coated with Zinc divalent ions to impart osteogenic properties. The physico-chemical characterization of scaffold, such as FTIR, XRD, and SEM studies was carried out. The biological characterization showed that the scaffolds were compatible with MSCs and promoted osteoblast differentiation which was confirmed at both cellular and molecular levels. The cellular construct increased calcium deposition, analyzed by alizarin red staining and ALP activity at cellular level. At the molecular level, the osteoblast markers expression such as Runx2 and type 1 collagen mRNAs, and osteonectin (ON) and osteocalcin (OC) secretory proteins were increased in the presence of scaffold. Overall, the current study recommends that MSCs can be easily obtained from human waste OFF, and grown in standard in vitro conditions. Successful growth of such MSCs with CS/PCL/Zn scaffold opens new avenues in utilizing the cell source for bone tissue engineering.
Assuntos
Materiais Biocompatíveis , Regeneração Óssea/fisiologia , Líquido Folicular/fisiologia , Folículo Ovariano/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Adulto , Materiais Biocompatíveis/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Células Cultivadas , Quitosana/administração & dosagem , Feminino , Líquido Folicular/citologia , Líquido Folicular/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais , Recuperação de Oócitos/métodos , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Folículo Ovariano/efeitos dos fármacos , Poliésteres/administração & dosagem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos , Zinco/administração & dosagemRESUMO
BACKGROUND: The pathobiology of prostate cancer-induced bone pain (PCIBP) is underpinned by both inflammatory and neuropathic components. Here, we used a rat model of PCIBP to assess the analgesic efficacy of a glycine transporter 2 (GlyT2) inhibitor (N-(6-((1,3-dihydroxypropan-2-yl)amino)-2-(dimethylamino)pyridin-3-yl)-3,5-dimethoxy-4-(4-(trifluoromethyl)phenoxy) benzamide) relative to two clinically available adjuvant drugs that are recommended for the relief of neuropathic pain, viz, pregabalin and duloxetine. METHODS: PCIBP was induced in male Wistar Han rats following intra-tibial injection (ITI) of rat prostate cancer (AT3B) cells into the left tibia. Sham-rats received an ITI of heat-killed AT3B cells. PCIBP rats with fully developed mechanical allodynia in the ipsilateral hindpaws as assessed using von Frey filaments, received single oral (p.o.) bolus doses of the GlyT2 inhibitor (3-30 mg/kg), pregabalin (3-100 mg/kg), duloxetine (3-100 mg/kg), or vehicle. Baseline paw withdrawal thresholds (PWTs) were determined in the ipsilateral (injured side) and contralateral hindpaws immediately prior to dosing and at scheduled times for 3 h post dosing in individual animals. RESULTS: Single oral bolus doses of the GlyT2 inhibitor (3-30 mg/kg) evoked partial pain relief at the doses tested in the ipsilateral hindpaws of PCIBP rats without any discernible behavioural side effects. By contrast, single oral bolus doses of pregabalin at 10-100 mg/kg evoked dose-dependent and complete alleviation of mechanical allodynia. By comparison, single oral bolus doses of duloxetine at doses up to 100 mg/kg lacked efficacy. CONCLUSION: Oral administration of this GlyT2 inhibitor evoked partial pain relief in PCIBP rats and did not evoke central nervous system side effects in contrast to GlyT2 inhibitors reported by others.
Assuntos
Dor do Câncer/tratamento farmacológico , Cloridrato de Duloxetina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Glicina/antagonistas & inibidores , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Pregabalina/farmacologia , Neoplasias da Próstata/fisiopatologia , Analgésicos/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Dor do Câncer/etiologia , Modelos Animais de Doenças , Hiperalgesia/metabolismo , Masculino , Neuralgia/etiologia , Medição da Dor/métodos , Limiar da Dor/efeitos dos fármacos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/metabolismo , Ratos , Ratos WistarRESUMO
INTRODUCTION: Endogenous or exogenous (corticosteroid-induced) glucocorticoids (GCs) excess represents, together with diabetes, the most common cause of secondary osteoporosis. AREAS COVERED: We present a comprehensive overview about the pathophysiology, clinical management and treatment of GCs induced osteoporosis (GIOP). According to PRISMA guidelines, a literature search identifying articles about bone and GCs was done. EXPERT OPINION: Despite the progress over the years and the increase in therapeutic options, there still are controversial issues about the management of GIOP. These mainly include the failure of BMD or FRAX to completely account for the rapid increase in fracture risk of most GC-treated patients, the understanding about the independent contribution on bone fragility of the underlying disease requiring GCs therapy, and the necessity of clearer information about the anti-fracture efficacy and long term-safety of most therapeutic options. Moreover, there are no specific indications for the management of bone fragility in endogenous hypercortisolism. Notwithstanding the above limitations there is a general consensus to recommend an assessment of fracture risk in all individuals >40 years committed to receive (or continuing) high dose (>7.5 mg of prednisone equivalent) GCs for ≥3 months and in all patients with fragility fracture history.
Assuntos
Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Fraturas por Osteoporose/etiologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Glucocorticoides/administração & dosagem , Humanos , Adesão à Medicação , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/prevenção & controle , Guias de Prática Clínica como AssuntoRESUMO
The treatment of pets, service animals, and pre-clinical research subjects with radionuclides raises concern for the safety of the people who interact with the animals after their treatment. Three treatments of skeletal conditions in dogs are considered in this study: Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid, which is a bone-seeking radiopharmaceutical; unencapsulated Y permanent interstitial implants, which are sometimes called "liquid brachytherapy"; and Sn radiosynoviorthesis, which is also called radiosynovectomy. External exposure rate readings of the Sm and Sn treatments, and Monte Carlo simulations of Sn at a distance of 1 m and of all three in direct contact with tissue were analyzed for doses. Dogs that have received any of these treatments using typically administered activities may be released from radiation safety isolation immediately after treatment from the standpoint of external exposure. People should avoid prolonged close proximity, such as sleeping with a treated dog, for three weeks following an Y interstitial implant or for a month following Sn radiosynoviorthesis. No such avoidance is necessary after treatment with Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid.
Assuntos
Osso e Ossos/efeitos da radiação , Exposição à Radiação/análise , Segurança , Animais , Osso e Ossos/efeitos dos fármacos , Cães , Método de Monte Carlo , Ácidos Fosforosos/química , Ácidos Fosforosos/farmacologiaRESUMO
BACKGROUND: Osteoporosis is a bone disease identified by disordering of bone formation and resorption cells. It increases the risk of bone fragility and fracture. Autocrine and paracrine signalling of osteoclasts and osteoblasts plays an important role in the regulation of bone remodelling. Calcitonin is an approved pharmacologic agent for the treatment of osteoporosis. METHODS: A novel mathematical model comprising the interaction among osteoclasts and osteoblasts cells with intermittent administration of calcitonin has been presented to study the dynamics of osteoporotic bone. The stability of model and sensitivity of parameters are also discussed. FINDINGS: The population of osteoclastic and osteoblastic cells has been predicted via numerical simulation. The results of Monte Carlo sensitivity analysis are shown via tornado diagram. INTERPRETATION: It is concluded that intermittent administration of calcitonin is an effective therapy for the treatment of osteoporosis.
Assuntos
Osso e Ossos/efeitos dos fármacos , Hormônios/farmacologia , Modelos Biológicos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Humanos , Método de Monte Carlo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacosRESUMO
INTRODUCTION: Recently several new approaches were emerging in bone tissue engineering to develop a substitute for remodelling the damaged tissue. In order to resemble the native extracellular matrix (ECM) of the human tissue, the bone scaffolds must possess necessary requirements like large surface area, interconnected pores and sufficient mechanical strength. MATERIALS AND METHODS: A novel bone scaffold has been developed using polyurethane (PE) added with wintergreen (WG) and titanium dioxide (TiO2). The developed nanocomposites were characterized through field emission scanning electron microscopy (FESEM), Fourier transform and infrared spectroscopy (FTIR), X-ray diffraction (XRD), contact angle measurement, thermogravimetric analysis (TGA), atomic force microscopy (AFM) and tensile testing. Furthermore, anticoagulant assays, cell viability analysis and calcium deposition were used to investigate the biological properties of the prepared hybrid nanocomposites. RESULTS: FESEM depicted the reduced fibre diameter for the electrospun PE/WG and PE/WG/TiO2 than the pristine PE. The addition of WG and TiO2 resulted in the alteration in peak intensity of PE as revealed in the FTIR. Wettability measurements showed the PE/WG showed decreased wettability and the PE/WG/TiO2 exhibited improved wettability than the pristine PE. TGA measurements showed the improved thermal behaviour for the PE with the addition of WG and TiO2. Surface analysis indicated that the composite has a smoother surface rather than the pristine PE. Further, the incorporation of WG and TiO2 improved the anticoagulant nature of the pristine PE. In vitro cytotoxicity assay has been performed using fibroblast cells which revealed that the electrospun composites showed good cell attachment and proliferation after 5 days. Moreover, the bone apatite formation study revealed the enhanced deposition of calcium content in the fabricated composites than the pristine PE. CONCLUSION: Fabricated nanocomposites rendered improved physico-chemical properties, biocompatibility and calcium deposition which are conducive for bone tissue engineering.
Assuntos
Osso e Ossos/fisiologia , Poliuretanos/farmacologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Osso e Ossos/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Teste de Materiais , Nanocompostos/química , Nanocompostos/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração , Termogravimetria , Titânio/farmacologia , Molhabilidade , Difração de Raios XRESUMO
Currently, bio-mimetic material synthetic processes are involved in bone implant design which is closely related to natural bone. In this work, Zinc, Cerium and Selenium substituted hydroxyapatite/ Poly (sorbitol sebacate glutamate) (Zn, Ce, Se-HAP/PSSG, M-HAP/PSSG) composite was prepared by sol-gel method as a bio-mimetic materials for bone implantation. The physiochemical characterizations of M-HAP/PSSG was analyzed by Fourier transform infra red (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) equipped with energy dispersive X-ray analysis (EDX) and High resolution transmission electron microscopy (HRTEM). Then, the prepared M-HAP/PSSG composite was compared with HAP/PSSG, Zn-HAP/PSSG, Ce-HAP/PSSG and Se-HAP/PSSG composites in order to evaluate the influence of single minerals on HAP matrix. Then the coating ability of the final better M-HAP/PSSG composite on surface treated titanium (Ti) was investigated to evaluate the perfection of implant material. The higher micro-hardness was observed on M-HAP/PSSG composite coated Ti (305.92⯱â¯20.42) due to the presence of multi-minerals as well as the co-polymer PSSG when compared with M-HAP coated Ti plate (273.0⯱â¯15.75). The bio-compatibility and osteogenic activity evaluation of all prepared composite on human osteoblasts MG-63 cells shows that the better cell attachment, proliferation and differentiation was observed by M-HAP/PSSG bio-composites when compared with other composites. Histological staining and X-ray photographs of in-vivo rat model confirms that the formation of new tibial bone when the defected rat was treated with M-HAP/PSSG composite coated Ti implant. In conclusion, the bio-composite M-HAP/PSSG is better scaffold for coating on the surface of Ti implant for orthopedic implantation.
Assuntos
Osso e Ossos/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Durapatita/farmacologia , Implantes Experimentais , Minerais/farmacologia , Sorbitol/farmacologia , Titânio/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Antibacterianos/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Durapatita/química , Dureza , Humanos , Masculino , Testes de Sensibilidade Microbiana , Osteogênese/efeitos dos fármacos , Ratos Wistar , Regeneração/efeitos dos fármacos , Sorbitol/síntese química , Sorbitol/química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Natação , Difração de Raios XRESUMO
ASB20123, a C-type natriuretic peptide/ghrelin chimeric peptide, was designed as a novel peptide and demonstrated full agonistic activity for natriuretic-peptide receptor B and a significantly longer half-life in plasma compared with the native peptide. We researched the toxicological profile of ASB20123, the correlation between the morphological change of the epiphyseal plate and bone and cartilage toxicity, and biomarkers to detect the toxicity. ASB20123 was systemically administered to male and female rats at daily dose levels of 0.5, 1.5, and 5.0 mg/kg/day for 4 weeks. In this study, toxicity was observed as changes related to bone and cartilage tissues, and no other toxicological changes were observed in all animals. Next, ASB20123 was administered to 12-month-old rats with a little epiphyseal plate. The toxic changes related to bone and cartilage tissues were not observed in any animal with a closed epiphyseal plate, indicating that the toxic changes were triggered by the growth-accelerating effect on the bone and cartilage. Furthermore, we searched for the biomarker related to the bone and cartilage toxicity using rats treated with ASB20123 at doses of 0.005, 0.05, 0.5, and 5.0 mg/kg/day for 4 weeks. A close correlation between necrosis/fibrosis in the epiphysis and metaphysis and thickness of the epiphyseal plate in the femur was confirmed in this study. A decrease in the bone mineral density (BMD) of the femur also was associated with the appearance of bone toxicity. These results indicated that the toxicity of ASB20123 was limited to bone- and cartilage-specific changes, and these changes were triggered by an excessive growth accelerating effect. Furthermore, our data suggested that the thickness of the epiphyseal plate and BMD could be reliable biomarkers to predict bone toxicity.
Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Peptídeo Natriurético Tipo C/farmacologia , Animais , Biomarcadores , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Epífises/efeitos dos fármacos , Feminino , Lâmina de Crescimento/efeitos dos fármacos , Masculino , Peptídeo Natriurético Tipo C/efeitos adversos , Peptídeo Natriurético Tipo C/análogos & derivados , RatosRESUMO
Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated mechanisms are studied and analyzed in laboratory animals in order to prevent them from occurring in humans. Rodents such as rats and mice have commonly been used in such studies because of their similarity to humans. In 1959, James G. Wilson designed, developed, and tested a protocol on how to observe and analyze structural malformations in rodent fetuses, which included: external examination, skeletal evaluation, soft tissue analysis, and data collection/analysis. For standardization purposes, i.e., to normalize findings from one lab to another, it is important that this protocol be followed with precision. Although many years have passed since Wilson initially created this protocol, it is still widely used to this day, and only minor changes have been made to his instructions such as the chemical reagents used in the experiments and methods of analysis of the experimental data. Such testing has resulted in major advances in the dissemination of teratology information, including the identification of an increasing number of teratogens and the understanding of the pathogenesis of birth defects. While mechanistically birth defect prevention will include the understanding of individual genomes and pharmacogenomics, overall, morphological assessment will still be required as an integral part of birth defects research. As the interaction between teratogenic and genetic factors is better understood, it is anticipated that the incidence of most types of defects will substantially be reduced.
Assuntos
Anormalidades Induzidas por Medicamentos/diagnóstico , Anormalidades Congênitas/diagnóstico , Teratogênicos/toxicidade , Anormalidades Induzidas por Medicamentos/genética , Animais , Osso e Ossos/anormalidades , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/embriologia , Anormalidades Congênitas/genética , Feminino , Feto/anormalidades , Feto/efeitos dos fármacos , Humanos , Camundongos , Gravidez , RatosRESUMO
BACKGROUND: Resolvin D1 (RvD1), an important member of resolvins, exerts a wide spectrum of biological effects, including resolution of inflammation, tissue repair, and preservation of cell viability. The aim of the present study is to investigate the anti-arthritic potential and clarify the bone protective actions of RvD1 in vitro and in vivo. METHODS: RAW264.7 cells were treated with 50 ng/ml LPS for 72 h in the presence or absence of RvD1 (0-500 nM). Primary human monocytes were treated with M-CSF + RANKL for 14 days ± RvD1 (0-500 nM) with or without siRNA against RvD1 receptor FPR2. Expressions of inflammatory mediators, degrading enzymes, osteoclasts (OC) formation, and bone resorption were analyzed. The therapeutic effect of RvD1 (0-1000 ng) was carried out in murine collagen antibody-induced arthritis. Arthritis scoring, joint histology, and inflammatory and bone turnover markers were measured. RESULTS: RvD1 is not toxic and inhibits OC differentiation and activation. It decreases bone resorption, as assessed by the inhibition of TRAP and cathepsin K expression, hydroxyapatite matrix resorption, and bone loss. In addition, RvD1 reduces TNF-α, IL-1ß, IFN-γ, PGE2, and RANK and concurrently enhances IL-10 in OC. Moreover, in arthritic mice, RvD1 alleviates clinical score, paw inflammation, and bone and joint destructions. Besides, RvD1 reduces inflammatory mediators and markedly decreases serum markers of bone and cartilage turnover. CONCLUSION: Our results provide additional evidence that RvD1 plays a key role in preventing bone resorption and other pathophysiological changes associated with arthritis. The study highlights the clinical relevance of RvD1 as a potential compound for the treatment of inflammatory arthritis and related bone disorders.
Assuntos
Artrite Experimental/prevenção & controle , Ácidos Docosa-Hexaenoicos/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos , Animais , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Células RAW 264.7RESUMO
There are limited reports of radiologically confirmed fractures and bone health monitoring in with Duchenne muscular dystrophy. We performed a retrospective study of 91 boys, with a median age of 11.0 years, who are currently managed in Scotland with the aim to assess the frequency of radiologically confirmed fractures and report on bone health monitoring in relation to International Care Consensus Guidance. Of these boys, 59 (65%) were receiving glucocorticoid (GC) therapy and 23 (25%) had received previous treatment. Of those currently on GC, 37 (63%) had an assessment of bone mineral density and none had routine imaging for vertebral fractures during the study period. Of the 91 boys, 44 (48%) had sustained at least one symptomatic radiographically confirmed fracture. The probability of sustaining a first symptomatic fracture was 50% by 12.8 years old (95%CI: 12.1, 13.6). The most common sites for non-vertebral fracture were the femur and tibia. In this review of boys with DMD, almost half had sustained at least one radiologically confirmed symptomatic fracture. There is a need for standardized bone health monitoring in DMD that includes routine imaging of the spine to identify vertebral fractures, given the persistence of insult to the skeleton in these boys.
Assuntos
Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/terapia , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/terapia , Adolescente , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Criança , Fraturas Ósseas/complicações , Fraturas Ósseas/epidemiologia , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/epidemiologia , Estudos Retrospectivos , EscóciaRESUMO
Phosphorus (P) is essential for building and maintaining a healthy and strong skeleton. Moreover, dietary P supply may play a role for bone turnover, and the excretion of bone turnover metabolites may be useful as markers for sufficient dietary P supply. The objective was to study the long-term effects of low, medium, and high dietary P supply on bone metabolism in terms of serum concentration and urinary excretion of bone turnover components and metabolites in healthy growing-finishing pigs compared with bone mineral content (BMC) and bone mineral density (BMD) of humerus and femur. Pigs were fed diets containing low [LP; 4.1 g/kg dry matter (DM)], medium (MP; 6.2 g/kg DM), or high dietary P (HP; 8.9 g/kg DM) from 39.7 kg body weight (BW) until slaughter at 110 kg BW. Urine and blood were collected at 40, 70, and 110 kg BW while bones were collected at slaughter. Serum was analyzed for osteocalcin (OC), bone alkaline phosphatase (BAP), and C-terminal telopeptides of type I collagen (CTX-I), whereas urine was analyzed for pyridinoline (PYD), deoxypyridinoline (DPD), CTX-I, hydroxylysine (HYL), galactosyl-hydroxylysine (GAL-HYL), glycosyl-galactosyl-hydroxylysine (GLC-GAL-HYL), and hydroxyproline (HYP). Humerus and femur were analyzed for BMC and BMD. The LP diet caused reduced OC and increased BAP and CTX-I concentrations in serum. Furthermore, BAP was increased in response to the HP diet. Urine metabolites of bone resorption were all increased in pigs fed the LP diet, but only a few responses were obtained in response to the HP diet. Furthermore, age-related decreases were identified for BAP, HYL, GAL-HYL, and GLC-GAL-HYL. Bone mineral content and BMD were markedly lowered in pigs fed the LP diet but were not affected in pigs fed the HP diet. In conclusion, OC, BAP, and CTX-I in serum have proved useful for P adequacy in growing-finishing pigs. In addition, urine bone resorption metabolites have also proved useful for P adequacy and analysis of PYD, DPD, and CTX-I was considered to be the most relevant markers due to their specificity for bone and their negative correlation with BMD, BMC, ash, calcium (Ca), and P contents. Finally, DPD may be the preferred marker in long-term P feeding assessments.
Assuntos
Biomarcadores/análise , Densidade Óssea/efeitos dos fármacos , Cálcio da Dieta/farmacologia , Fósforo na Dieta/farmacologia , Suínos/fisiologia , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Dieta/veterinária , FemininoRESUMO
BACKGROUND: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. MATERIALS AND METHODS: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. RESULTS: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). CONCLUSIONS: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.
Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Testosterona/deficiência , Testosterona/farmacologia , Osso e Ossos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos , Testosterona/metabolismoRESUMO
Estrogen deficiency following menopausal provokes alveolar bone loss, remodeling and inflammation. Eugenol is a phenolic compound with wide dental applications and anti-inflammatory properties. In the present study, the potential protective role of eugenol against alveolar bone deformities was investigated in an ovariectomized (OVX) rodent model. Two doses of eugenol (2.5 and 5 mg/kg/d) were administered to OVX animals for 12 weeks. In Serum, markers of bone metabolism and pro-inflammatory cytokines were estimated using ELISA. Alveolar bone morphometry was analyzed using high-resolution micro-computed tomography (CT). Bone histological analysis (H&E stain) was also performed. Alveolar bone expression of osteoclastogenesis modulating factors, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-b ligand (RANKL) and inflammatory mediators, were measured using immunohistochemistry. Eugenol failed to correct elevated body weights and uterine atrophy in OVX rats. The significant elevation of bone metabolic markers and inflammatory cytokines in OVX animals were markedly improved by eugenol treatment, particularly the higher dose. Eugenol treatment considerably attenuated morphometric trabecular alterations of the alveolar bone and improved alveolar resorption and gingival infiltration. Alveolar bone of OVX animals showed augmented expression of RANKL, OPG and inflammatory cytokines, which were corrected by eugenol treatment. Alveolar bone loss and remodeling associated with estrogen insufficiency was ameliorated by eugenol owing to its anti-inflammatory properties, suggesting an extra dental impact for eugenol.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Osso e Ossos/efeitos dos fármacos , Eugenol/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estrogênios/deficiência , Eugenol/administração & dosagem , Feminino , Mediadores da Inflamação/metabolismo , Menopausa , Ovariectomia , Ratos , Ratos Wistar , Microtomografia por Raio-XRESUMO
Clinical trials and meta-analyses investigating bisphosphonates as an adjuvant breast cancer therapy have shown a consistent trend, with postmenopausal women and women receiving ovarian suppression with gonadotropin-releasing hormone therapy gaining improved breast cancer outcomes with the use of adjuvant bisphosphonate therapy. The interpretation of these data is controversial, because the primary endpoints of the majority of adjuvant bisphosphonate studies have been negative. Pros and cons as well as the value of adjuvant bisphosphonate therapy are discussed here.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Difosfonatos/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Neoplasias da Mama/patologia , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , HumanosRESUMO
Foods consist of a large number of different nutrients that are contained in a complex structure. The nature of the food structure and the nutrients therein (i.e., the food matrix) will determine the nutrient digestion and absorption, thereby altering the overall nutritional properties of the food. Thus, the food matrix may exhibit a different relation with health indicators compared to single nutrients studied in isolation. The evidence for a dairy matrix effect was presented and discussed by an expert panel at a closed workshop, and the following consensus was reached: 1) Current evidence does not support a positive association between intake of dairy products and risk of cardiovascular disease (i.e., stroke and coronary heart disease) and type 2 diabetes. In contrast, fermented dairy products, such as cheese and yogurt, generally show inverse associations. 2) Intervention studies have indicated that the metabolic effects of whole dairy may be different than those of single dairy constituents when considering the effects on body weight, cardiometabolic disease risk, and bone health. 3) Different dairy products seem to be distinctly linked to health effects and disease risk markers. 4) Different dairy structures and common processing methods may enhance interactions between nutrients in the dairy matrix, which may modify the metabolic effects of dairy consumption. 5) In conclusion, the nutritional values of dairy products should not be considered equivalent to their nutrient contents but, rather, be considered on the basis of the biofunctionality of the nutrients within dairy food structures. 6) Further research on the health effects of whole dairy foods is warranted alongside the more traditional approach of studying the health effects of single nutrients. Future diet assessments and recommendations should carefully consider the evidence of the effects of whole foods alongside the evidence of the effects of individual nutrients. Current knowledge gaps and recommendations for priorities in future research on dairy were identified and presented.
Assuntos
Laticínios , Dieta , Gorduras na Dieta/farmacologia , Comportamento Alimentar , Proteínas do Leite/farmacologia , Minerais/farmacologia , Valor Nutritivo , Disponibilidade Biológica , Peso Corporal/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , HumanosRESUMO
For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.