The biological properties of calcium phosphate-derived materials are strongly influenced by changes in Ca/P stoichiometry and grain size, which have not yet been fully elucidated to date. For this reason, the objective of this in vitro study was to understand osteoblast (bone forming cells) adhesion on nanoparticulate calcium phosphates of various Ca/P ratios. A group of calcium phosphates with Ca/P ratios between 0.5 and 2.5 were obtained by adjusting the Ca/P stoichiometry of the initial reactants necessary for calcium phosphate precipitation. For samples with 0.5 and 0.75 Ca/P ratios, tricalcium phosphate (TCP) and Ca(2)P(2)O(7) phases were observed. In contrast, for samples with 1.0 and 1.33 Ca/P ratios, the only stable phase was TCP. For samples with 1.5 Ca/P ratios, the TCP phase was dominant, however, small amounts of the hydroxyapatite (HA) phase started to appear. For samples with 1.6 Ca/P ratios, the HA phase was dominant. Last, for samples with 2.0 and 2.5 Ca/P ratios, the CaO phase started to appear in the HA phase, which was the dominant phase. Moreover, the average nanometer grain size, porosity (%), and the average pore size decreased in general with increasing Ca/P ratios. Most importantly, results demonstrated increased osteoblast adhesion on calcium phosphates with higher Ca/P ratios (up to 2.5). In this manner, this study provided evidence that Ca/P ratios should be maximized (up to 2.5) in nanoparticulate calcium phosphate formulations to increase osteoblast adhesion, a necessary step for subsequent osteoblast functions such as new bone deposition.
Tendinopathy is a serious health problem and its etiology is not fully elucidated. Among intrinsic and extrinsic predisposing factors of tendinopathy, the impact of therapeutic agents, especially fluoroquinolone (FQ) group antibiotics, is recently being recognized. FQs are potent bactericidal agents widely used in various infectious diseases, including community acquired pneumonia and bronchitis, chronic osteomyelitis, traveler's diarrhea, typhoid fever, shigellosis, chronic bacterial prostatitis, uncomplicated cervical and urethral gonorrhea and prophylaxis of anthrax. FQs have an acceptable tolerability range. However, many lines of evidence for developing tendinitis and tendon rupture during FQ use have resulted in the addition of a warning in patient information leaflets. FQ-induced tendinopathy presents a challenge for the clinician because healing response is poor due to low metabolic rate in mature tendon tissue and tendinopathy is more likely to develop in patients who are already at high risk, such as elderly, solid organ transplant recipients and concomitant corticosteroid users. FQs become photo-activated under exposure to ultraviolet light, and this process results in formation and accumulation of intracellular reactive oxygen species (ROS). The subsequent FQ-related oxidative stress disturbs mitochondrial functions, leading to apoptosis. ROS overproduction also has direct cytotoxic effects on extracellular matrix components. Understanding the mechanisms of the FQ-associated tendinopathy may enable designing safer therapeutic strategies, hence optimization of clinical response. In this review, we evaluate multi-factorial etiology of the FQ-induced tendinopathy and discuss proposed preventive measures such as antioxidant use and protection from natural sunlight and artificial ultraviolet exposure.
All the statins tested are associated with calcific tendinopathy risk of which full awareness is required during everyday medical practice. However, statin-associated improvement of bone biomechanical properties is a favourable feature which may add to their beneficial effects in atherosclerotic cardiovascular disease, especially in the elderly.
-Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks. 6 weeks after treatment, the test animals were euthanised and Achilles tendon specimens were collected. A computer monitored tensile testing machine was utilised for biomechanical testing. The mean elastic modulus of the control group was significantly higher than that of the norfloxacin and pefloxacin groups (p < 0.05 and p < 0.01, respectively). The mean yield force (YF) of the control group was significantly higher than those of ciprofloxacin, norfloxacin and pefloxacin groups (p < 0.001, p < 0.05 and p < 0.01, respectively). The mean ultimate tensile force (UTF) of the control group was significantly higher than of the ciprofloxacin, norfloxacin, and pefloxacin groups (p < 0.001, p < 0.05 and p < 0.01, respectively). Hyaline degeneration and fibre disarrangement were observed in the tendons of the ciprofloxacin, pefloxacin, and ofloxacin treated-groups, whereas myxomatous degeneration was observed only in the ciprofloxacin and pefloxacin groups. In conclusion, these findings in our rat model reveal significant deterioration of biomechanical parameters following fluoroquinolone exposure, and indicate significantly higher biomechanical toxicity for ciprofloxacin and pefloxacin.
ObjectiveThe aim of the present study was to evaluate histopathological and biomechanical effects of isotretinoin on Achilles tendon.Materials & methodsSixteen rats were divided into two groups including the control group (n = 8) and isotretinoin group (n = 8). The control group received 1.42 ml/kg soy oil per day whereas the isotretinoin group received 15 mg/kg/day (gavage dose 1.42 ml/kg) isotretinoin dissolved in soy oil through gavage method for 6 weeks. Achilles tendons were excised at the end of week 6. The tendon samples were evaluated by hematoxylin-eosin under a light microscope. Quantitative evaluation was performed via Movin and Bonar scoring. A computer-monitored tensile testing machine was utilised for biomechanical testing. Biomechanical characteristics of the tendon samples (elastic modulus, yield force, ultimate tensile force) were measured.ResultsHistopathological evaluation revealed a significantly higher Movin and Bonar scores in histopathological evaluation. Movin score in isotretinoin group was 4.1 ± 2.5 and it was 2.3 ± 1.0 in control group (p = 0.032). Bonar score in isotretinoin group was 2.9 ± 1.4 and it was 1.6 ± 0.7 in control group (p = 0.022). In line with histopathological evaluation, biomechanical measurements in isotretinoin group (elastic modulus, yield force, ultimate tensile force) were significantly lower than the control group. Elastic modulus in isotretinoin group was 227 ± 27.7 N/mm2 and in control group it was 281.7 ± 38.7 N/mm2 (p = 0.006). In isotretinoin group; yield force was 33.7 ± 4.3 Pa and in control group it was 40.8 ± 5.9 Pa (p = 0.021). Ultimate tensile force in isotretinoin group was 35.7 ± 4.2 Pa and in control group it was 44 ± 7 Pa (p = 0.009).ConclusionThe present study detected histopathological and biomechanical negative effect of isotretinoin on Achilles tendon. Therefore, isotretinoin should be questioned in medical history of patients with tendinopathy.
SummaryDefects in long bones are known to lead to increased risk of pathologic fracture. Holes weaken bones and increase the risk of fracture during bending, especially on exposure to torsional forces. Here, we investigated the effect of holes of varying numbers and sizes drilled into sheep femur bones on the resistance of the bone to torsional forces. Ninety-six fresh sheep femur bones were allocated to 8 groups, which were further subdivided into 4 groups of 3 bones each. In each group, 1 to 4 holes ranging from 2 to 5.5 mm were drilled into the femurs, and the bones were subjected to a rotation test. Forces that caused fractures and the force curves were measured and recorded. The effect of the number and size of the holes drilled in the femurs on the occurrence of fractures was compared using two-way analysis of variance, and Tukey's multiple comparison test was used for multiple comparisons. P<0.05 was considered statistically significant. We found that the resistance of a bone to torsional forces decreased significantly with increase in the number and size of the drilled holes (P<0.001). The rate of fractures increased as the number and sizes of the holes increased. The resistance of the bones to torsional forces decreased as the number of holes increased. We showed that the size of a defect in a bone is extremely important for torsional resistance and is, in fact, more important than the number of defects. Keywords: Fracture, Rotational forces, Bone, Femur, Sheep Koyun Femurlarında Çeşitli Boyutlardaki Deliklerin Kırık Oranları Üzerine Etkilerinin Değerlendirilmesi ÖzetUzun kemiklerdeki defektlerin patololojik kırığa neden olduğu bilinmektedir. Delikler özellikle torsiyonel güçlere maruz kalınca bükülme esnasında kemiği zayıflatır ve kırık riskini artırır. Buradaki çalışmamızda biz koyun femur kemiklerinde drille delinmiş çeşitli sayı ve boyutlardaki deliklerin etkilerini araştırdık. 96 tane taze koyun kemiği her biri ilaveten 3 kemiği içeren 4'lü alt gruplara bölünerek 8 gruba ayrıldı. Her bir grubta 2 mm'den 5.5 mm'ye kadar değişen 1'den 4'e kadar delikler femurlar delinerek açıldı ve kemikler rotasyon testine tabi tutuldular. Kırığa neden olan kuvvetler ve kuvvet eğrileri ölçüldü ve kayıt edildi. Delik açılan femurlarda kırık oluşturan deliklerin boyutları ve sayısının etkisi iki yönlü varyans analizi ve Tukey'in çoklu karşılaştırma testi ile mukayese edildi. P<0.05 istatistiksel olarak anlamlı bulundu. Dril ile delinmiş deliklerin boyut ve sayısında artma ile birlikte kemiğin torsiyonel kuvvetlere karşı direncinin önemli derecede azaldığını bulduk (P<0.001). Kırık oranı deliklerin sayısı ve boyutu arttıkça artmaktadır. Torsiyonel kuvvetlere karşı kemiğin direnci deliklerin sayısı arttıkça azalmaktadır. Biz bir kemik defektinin boyutunun torsiyonel direnç için oldukça önemli olduğunu ve gerçekte de defektlerin sayısının boyutuna göre daha etkili olduğunu gösterdik.
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