Quasi-static and dynamic properties of the intervertebral disc: experimental study and model parameter determination for the porcine lumbar motion segment.

PURPOSE: The study of axial loading is essential to determine the properties of intervertebral disc. The objectives of this work are (1) to quantify the mechanical properties of porcine lumbar intervertebral discs under static and cyclic compressive loading, and (2) to determine the parameters of a five-parameter rheological model for porcine and compare them with those obtained for human lumbar intervertebral discs. METHODS: Thus, the porcine lumbar motion segments were subjected to quasi-static and dynamic compression tests. The quasi-static tests were used to obtain the static stiffness coefficient at different strain rates, while the data from the cyclic compressive tests were used to both determine the dynamic stiffness coefficient and to be fitted in a 5-parameter model, in order to simulate the creep response of the porcine intervertebral discs. RESULTS: The results demonstrated that dynamic stiffness coefficient of porcine discs is between four and ten times higher than the static stiffness coefficient, depending on load applied. The parameters of the rheological model suggested a low permeability of nucleus and endplate during the fast response of porcine discs. In addition, the fast response in terms of displacement is four times higher than those documented for human discs. CONCLUSIONS: This study revealed that care must be taken on the comparison between porcine and human discs, since they present different behaviour under quasi-static and dynamic compressive loading.

Long-Term Creep Behavior of the Intervertebral Disk: Comparison between Bioreactor Data and Numerical Results.

The loaded disk culture system is an intervertebral disk (IVD)-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands), which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, eight goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Paul et al., 2012, 2013; Detiger et al., 2013), four of these IVDs were kept in physiological condition (control) and the other four were previously injected with chondroitinase ABC (CABC), in order to promote degenerative disk disease (DDD). The loading profile intercalated 16 h of activity loading with 8 h of loading recovery to express the standard circadian variations. The displacement behavior of these eight IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced finite element (FE) model. The simulations were run on a custom FE solver (Castro et al., 2014). The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in two of the four IVDs. The four control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected). However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles, and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery periods.

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics]. / Polimorfismo del gen de aldosa reductasa y velocidad de aparición de retinopatía en diabéticos no insulinodependientes.

BACKGROUND: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. AIM: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. PATIENTS AND METHODS: A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. RESULTS: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. CONCLUSIONS: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.