Growth factors of the TGF-b family in blood of achondroplasia patients at stages of orthopedic treatment

Author(s):  
Е.П. Выхованец ◽  
Н.В. Сакулин ◽  
С.Н. Лунева ◽  
Н.В. Накоскина ◽  
О.В. Климов

Наиболее важной задачей при дистракционном остеосинтезе является создание простых и эффективных способов контроля темпов дистракции позволяющих производить удлинение конечности в оптимальном режиме у различных групп пациентов. Цель исследования - анализ содержания сывороточных концентраций TGFb-1 и TGFb-2, BMP-4 и BMP-6 у лиц при увеличении роста с косметической целью и у пациентов с ахондроплазией на этапах дистракционного остеогенеза при удлинении голени методом Илизарова. Методика. Определение ростовых факторов проводили на комплексе оборудования фирмы Thermofisher (США): детектор Multiscan FC, встряхиватель iEMS, автоматический промыватель планшет WellWash. Для измерения концентрации факторов в сыворотке крови использовали наборы для иммуноферментного анализа (ИФА) eBioscience и RayBiotech Inc. (США). Результаты . Показано, что в сыворотке крови людей с ахондроплазией, еще до какого-либо ортопедического лечения концентрации TGF-b2 и ВМР-4, ниже, а TGF-b1 и ВМР-6, выше, чем концентрации этих факторов у людей при увеличении роста с косметической целью. У последних удлинение конечностей сопровождается возрастанием содержания в сыворотке крови факторов TGF-b1 и TGF-b2 на этапах начала и середины процесса дистракции. У пациентов с ахондроплазией, наблюдается обратная динамика: концентрация данных факторов (ВМР-4 и ВМР-3) в крови ахондропатов к концу дистракции увеличивается в 3,5 и 2 раза соответственно, снижаясь в периоде фиксации. Заключение. Таким образом, у пациентов с ахондроплазией происходит нарушение этапности процессов костного ремоделирования. Elaboration of simple and effective ways for managing the distraction rate to provide an optimum regimen of limb lengthening for different groups of patients is an important task in implementation of transosseous osteosynthesis. The aim of this study was to analyze blood serum concentrations of TGFb-1, TGFb-2, BMP-4, and BMP-6 in individuals undergoing cosmetic height increase and patients with achondroplasia at different stages of distraction osteogenesis in tibial lengthening using the Ilizarov method. Methods. Concentrations of growth factors were measured using a set of Thermofisher (USA) equipment, including a Multiscan FC detector, iEMS Shaker, and automatic WellWash Washer and ELISA kits (eBioscience and RayBiotech Inc., USA). Results. Serum concentrations of TGFb-2 and BMP-4 were lower and TGFb-1 and BMP-6 were higher in achondroplasia patients than in individuals with cosmetic height increase even before any orthopedic treatment. Long bone lengthening for cosmetic height increase was associated with increases in serum levels of TGFb-1 and TGFb-2 at the start and in the middle of distraction. In achondroplasia patients, opposite changes were observed; serum concentrations of BMP-4 and BMP-3 increased 3.5 and 2 times, respectively, by the end of distraction and decreased during fixation. Conclusion. Therefore, we observed a disorder of the stage-by-stage bone remodeling process in achondroplasia patients.

2013 ◽  
Vol 31 (12) ◽  
pp. 1966-1970 ◽  
Author(s):  
Maksim V. Stogov ◽  
Svetlana N. Luneva ◽  
Konstantin I. Novikov

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Harald Binder ◽  
Stefan Eipeldauer ◽  
Markus Gregori ◽  
Leonard Höchtl-Lee ◽  
Anita Thomas ◽  
...  

Objectives.Circulating levels of VEGF-A (Vascular Endothelia Growth Factor-A), TGF-β1 (Transforming Growth Factor-beta 1), and M-CSF (Macrophage-Colony Stimulating Factor) were found to be predictors of bone healing and therefore prognostic criteria of delayed bone healing or nonunion. The aim of this study was to evaluate a potential rise of these markers in patients with multiple fractures of long bones compared to patients with single fractured long bone.Methods.92 patients were included in the study and finally after excluding all female patients 45 male patients were left for final analysis and divided into the single or multiple fracture group. TGF-β1, M-CSF, and VEGF-A serum levels were analysed over a time period of two weeks.Results.MCSF serum concentrations were higher in the group with multiple fractures as also TGF-β1 serum concentrations were at one and two weeks after trauma. No statistically significant difference was observed in the VEGF-A serum concentrations of both groups at either measurement point.Conclusion.We did observe a correlation between the quantity of the M-CSF and TGF-β1 expressions in serum and the number of fractured bones; surprisingly there was no statistically significant difference in the serum levels between patients with single and multiple fractures of long bones.


1994 ◽  
Vol 266 (1) ◽  
pp. E129-E135 ◽  
Author(s):  
J. K. Yeh ◽  
J. F. Aloia ◽  
M. Chen ◽  
N. Ling ◽  
H. C. Koo ◽  
...  

Growth factors may be mediators of local and systemic factors that enhance bone formation. This study examined the effect of treadmill exercise and ovine growth hormone administration on levels of insulin-like growth factor I (IGF-I) in serum (ng/ml), long bone, and vertebrae and on bone formation rate. Forty female rats were divided into four groups: control; exercise (17 m/min, 1 h/day); growth hormone (0.05 mg.100 g-1.day-1); growth hormone plus exercise. After 9 wk of study, the serum levels of IGF-I were higher in the intervention groups than in the control group; however, the IGF-I concentration and the periosteal bone formation rate in the long bone were significantly higher only in the exercised rats. The IGF-I concentration and the cancellous bone formation rate in the vertebrae did not differ among the experimental groups. The vertebral and long bone formation rate were correlated with bone concentrations of IGF-I. Serum levels of IGF-I were also correlated with serum osteocalcin and the long bone formation but not with the vertebral bone formation. The association of bone formation with serum and bone IGF-I supports the suggestion that IGF-I is one of the growth factors that regulate bone formation, in particular as a mediator of the response of bone to exercise.


2011 ◽  
Vol 5 (4) ◽  
Author(s):  
Jinyong Wee ◽  
Robert E. Akins ◽  
William G. Mackenzie ◽  
Rahamim Seliktar ◽  
David G. Levine ◽  
...  

Distraction osteogenesis is a routine surgical procedure to lengthen a long bone. A fixed lengthening rate is typically used. We investigate measuring forces continuously and producing a variable distraction rate. A motorized distractor was instrumented with a load cell to measure the forces developed in a limb during distraction osteogenesis. The motor moves 2.6 μm at each step, with a variable frequency depending on the distraction rate. The forces were measured every 15 s and used to change the rate on the autodistractor. The autodistractor, load cell, data logger, controller, and battery pack were all mounted on a monolateral rail fixator, which was tested on a sheep that underwent tibial lengthening. Results show the feasibility of continually recording forces in vivo. The lengthening rate changed automatically, based around a threshold force of 300 N. Findings indicate that force readings are feasible and practical with a simple device. Force determination may provide an additional means to evaluate tissue integrity in real-time and away from the clinic. An automatic variable rate device could improve limb lengthening.


2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.


2021 ◽  
pp. 1-26
Author(s):  
Xue-min Huang ◽  
Yan-hua Liu ◽  
Han Zhang ◽  
Yuan Cao ◽  
Wei-feng Dou ◽  
...  

Abstract The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case-control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a 78-item semi-quantitative food frequency questionnaire. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography–tandem mass spectrometry. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines (RCS) were plotted to evaluate the dose-response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the ORs of the highest quartile were 0.45 (95%CI: 0.29-0.71, Ptrend = 0.001) for VD dietary intake and 0.26 (95%CI: 0.11-0.60, Ptrend = 0.003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0.02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0.02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.


Author(s):  
Magda Wiśniewska ◽  
Natalia Serwin ◽  
Violetta Dziedziejko ◽  
Małgorzata Marchelek-Myśliwiec ◽  
Barbara Dołęgowska ◽  
...  

Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 548
Author(s):  
Chia-Wen Lu ◽  
Yi-Chen Lee ◽  
Chia-Sheng Kuo ◽  
Chien-Hsieh Chiang ◽  
Hao-Hsiang Chang ◽  
...  

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 μg/L, 1043.45 ± 306.36 μg/L, and 1246.83 ± 538.13 μg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35–10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25–3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24–3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.


2020 ◽  
Vol 9 (12) ◽  
pp. 4104
Author(s):  
Lukas Zak ◽  
Thomas Manfred Tiefenboeck ◽  
Gerald Eliot Wozasek

Limb length discrepancy (LLD) is a common problem after joint-preserving hip surgeries, hip dysplasia, and hip deformities. Limping, pain, sciatica, paresthesia, and hip instability are common clinical findings and may necessitate limb-lengthening procedures. The study included five patients (two female and three male, mean age of 28 years (20–49; SD: 12)) with symptomatic limb length discrepancy greater than 2.5 cm (mean: 3.6 cm) after total hip arthroplasty (THA), hip dysplasia, or post-traumatic hip surgery. They underwent either ipsi- or contralateral intramedullary limb-lengthening surgeries using the PRECICE™ telescopic nail. All patients achieved complete bone healing and correction of the pelvic obliquity after intramedullary lengthening. None of the patients had a loss of proximal or distal joint motion. The mean distraction-consolidation time (DCT) was 3.8 months, the distraction index (DI) 0.7 mm/day, the lengthening index (LI) 1.8 months/cm, the consolidation index (CI) 49.2 days/cm, the healing index (HI) 1.1 months/cm, and the modified healing index (HI*) 34 days/cm. Intramedullary limb lengthening after LLD in cases of hip dysplasia, hip deformity, and various kinds of hip surgery is a useful and safe procedure in young patients to achieve equal limb length. No functional impairment of the preceded hip surgery was seen.


2021 ◽  
Author(s):  
Simone Marcella ◽  
Angelica Petraroli ◽  
Mariantonia Braile ◽  
Roberta Parente ◽  
Anne Lise Ferrara ◽  
...  

Abstract Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSAKIT WT and ROSA KIT D816V and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSAKIT WT, ROSAKIT D816V and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients.


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