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PubMed1982

Tracing of two-neuron pathways in the olfactory system by the aid of transneuronal degeneration: projections to the amygdaloid body and hippocampal formation.

Following an olfactory bulb lesion in guinea pig (2 to 3 days), neuronal degeneration occurs in several olfactory-bulb-related areas, primarily in the piriform cortex. The degenerating neurons, which are argyrophilic, are also found in the posterolateral cortical amygdaloid nucleus and the ventrolateral entorhinal cortex. It is suggested that the neurons degenerate because of a transneuronal effect due to a sudden loss of afferent input from the olfactory bulb, although a retrograde effect acting in concert with transneuronal factors cannot be excluded. Terminal degeneration can be identified in several areas outside the olfactory bulb projection area, and is interpreted as degeneration in the axons of the degenerating cortical neurons. Such terminal degeneration, which is best seen 3 to 4 days postoperatively, has been identified in part of the basolateral amygdaloid complex, in the basomedial amygdaloid nucleus, and in the temporal parts of the fascia dentata of the hippocampal formation. Terminal degeneration has also been observed in the deep layers of the anterior olfactory nucleus, the olfactory tubercle, the nucleus of the lateral olfactory tract, and the anterior amygdaloid area. All these projections, apparently, represent the second link in two-neuron pathways, where mitral or tufted cells in the olfactory bulb make up the first neuron. This interpretation was confirmed in control experiments in which areas of argyrophilic neurons coincided with the location of retrogradely labeled neurons following injection of fluorescent substances into several of the above-mentioned areas of terminal degeneration.

Afferent Pathways↗
PubMed1986

Age-dependent cell death in the olfactory cortex: lack of transneuronal degeneration in neonates.

Adult olfactory cortical neurons in layer IIa undergo fulminant transneuronal degeneration after removal of afferent olfactory bulb fibers (Price, '76, Neurosci Abst. 2:161; Heimer and Kalil, '78, J. Comp. Neurol. 178:559-609). This provides an unusual example of dependence of a mature population of neurons on axonal input. In order to investigate whether similar transneuronal degeneration occurs in immature animals, a series of rats were subjected to unilateral olfactory bulb removal at various ages during the first 3 postnatal weeks. The brains were examined for degeneration after short survivals by use of the de Olmos cupric silver method, which selectively stains degenerating neurons. In addition, animals with long survivals were examined with the HRP retrograde tracing method, in order to determine if cells that survive the acute effects of deafferentation develop normal patterns of connections. Young neurons are more resistant to the effects of olfactory bulb removal than more mature neurons. There was little degeneration of cortical neurons after bulb ablation during the first 2 postnatal weeks. Although layer IIa does not become distinct from layer IIb in these experimental animals, cells that have connections normally characteristic of the cells of layer IIa, and are situated at the superficial edge of layer II, were identified with the HRP method. The severity of transneuronal degeneration increases and becomes adultlike between the second and third postnatal weeks. This increase in transneuronal degeneration is temporally associated with a progressive reduction in axonal sprouting following deafferentation during the first 3 postnatal weeks, as described in the companion paper (Friedman and Price, '86). Thus, axon sprouting may "protect" the immature IIa neurons from the effects of removal of the fibers from the olfactory bulb. A period of normal cell death has also been identified in olfactory cortex by the use of the de Olmos cupric silver method. This cellular degeneration is much less severe and has a different time course and laminar distribution than the transneuronal degeneration produced by olfactory bulb ablation in adults. Although normal cell death appears to be potentiated by removal of the olfactory bulb on postnatal day 1, it is clearly a different process from the transneuronal reaction.

Age Factors↗
PubMed2001

Height of lumbar discs measured from radiographs compared with degeneration and height classified from MR images.

The relation between height of lumbar discs (measured from lateral radiographic views) and disc degeneration (classified from MR images) deserves attention in view of the wide, often parallel or interchanged use of both methods. The time sequence of degenerative signs and decrease of disc height is controversial. To clarify the issue, this cross-sectional study documents the relation between disc degeneration and disc height in a selected cohort. Forty-three subjects were selected at random from a cohort examined for potential disc-related disease caused by long-term lifting and carrying. From each subject a lateral radiographic view of the lumbar spine as well as findings from an MR investigation of (in most cases) levels T12/L1 to L5/S1 were available; thus, n = 237 lumbar discs were available for measurement and classification. Disc height was measured from the radiographic views with a new protocol compensating for image distortion and permitting comparison with normal, age- and gender-appropriate disc height. Degeneration as well as disc height were classified twice from MR images by independent observers in a blinded fashion. Disc degeneration classified from MR images is not related to a measurable disc height loss in the first stage of degeneration, whereas progressive degeneration goes along with progressive loss of disc height, though with considerable interindividual variation. Loss of disc height classified from MR images is on average compatible with loss of disc height measured from radiographs. In individual discs, however, classification of height loss from MR images is imprecise. The first sign of disc degeneration (a moderate loss of nucleus signal) precedes disc height decrease. As degeneration progresses, disc height decreases. Disc height decrease and progress of degeneration, however, appear to be only loosely correlated.

Adult↗
PubMed2003

Correlation between bone mineral density and intervertebral disk degeneration in pre- and postmenopausal women.

The purpose of this study was to investigate the relationship between intervertebral disk degeneration and bone mass. Magnetic resonance imaging was performed to evaluate lumbar disk degeneration according to Thompson's classification (grades 1 and 2, normal disk; grades 3, 4, and 5, degenerated disk), and bone mineral density (BMD) in the lumbar vertebrae, radius, and calcaneus was measured by dual-energy X-ray absorptiometry for 90 women (22-74 years old). The relationship between the grade of intervertebral disk degeneration and the BMD ( Z score) was analyzed in pre- and postmenopausal women. In premenopausal women, BMD was significantly higher at all measured sites in the degenerated disk group judged at the L5-S1 level than in the normal disk group ( P < 0.05). In postmenopausal women, BMD was significantly higher at the anteroposterior L2-L4, lateral L3, and calcaneus in the degenerated disk group judged at the L2-L3 level than in the normal disk group ( P < 0.05). BMD at the anteroposterior L2-L4 and calcaneus was significantly higher in the degenerated disk group judged at the L3-L4 level than in the normal disk group ( P < 0.05). In conclusion, the BMD of not only the lumbar vertebrae but also the calcaneus and radius was mutually related to lumbar intervertebral disk degeneration from an early stage of degeneration.

Adult↗
PubMed1984

Frequency spectra of the first heart sound and of the aortic component of the second heart sound in patients with degenerated porcine bioprosthetic valves.

To determine the usefulness of the frequency of heart sounds in the assessment of porcine bioprosthetic valve degeneration, frequency spectra of phonocardiograms of the first heart sound and the aortic component of the second sound were analyzed in 31 patients with degenerated porcine bioprosthetic valves. Comparisons were made with 35 control patients whose valves were inserted 1 month or less. Among 23 patients with degenerated porcine bioprosthetic valves in the mitral position, the dominant frequency of the first heart sound was 95 +/- 11 Hz, which exceeded the first sound in 18 controls (51 +/- 3 Hz) (p less than 0.01). The degenerated mitral porcine bioprosthetic valves of 14 patients showed calcification or fibrosis and the first heart sound in these patients was 115 +/- 16 Hz, which exceeded that of control subjects (p less than 0.001). The degenerated mitral porcine bioprosthetic valves of 9 patients showed torn leaflets only, and the first heart sound in these patients was 64 +/- 9 Hz, which did not differ from that of control subjects. In the aortic position, 8 valves were degenerated and the aortic component of the second sound was 109 +/- 12 Hz, which was higher than that in 17 control subjects (63 +/- 4 Hz) (p less than 0.001). Only 2 of these degenerated valves showed tears unaccompanied by calcific deposits or fibrosis, and the frequencies were comparable to that of control subjects. These observations indicate that the frequency of heart sounds in patients with degenerated porcine bioprosthetic valves becomes abnormally elevated when degeneration is accompanied by calcification or fibrosis, which causes the cusps to stiffen.

Aortic Valve↗
PubMed2006

The effect of exogenous melatonin administration on trabecular width, ligament thickness and TGF-beta(1) expression in degenerated intervertebral disk tissue in the rat.

Intervertebral disk (IVD) degeneration, a complex pathological condition of varying origins, causes low back pain. Degenerative changes in IVD tissue affect the adjacent vertebral structure, resulting in a decreased vertebral trabecular width. It has been suggested that transforming growth factor-beta 1 (TGF-beta(1)) may have a role in the repair of connective tissue, as it occurs in the IVD degeneration process. In this study, we investigated the effects of exogenous melatonin (MEL) administration on vertebral trabecular width, ligament thickness and TGF-beta(1) expression in degenerated IVD tissue. Fifteen adult male Swiss Albino rats were divided randomly into three groups; nonoperated control, operated degeneration, and MEL treatment groups. In the operated degeneration and MEL treatment groups, cuts were made parallel to the end plates in the posterior annulus fibrosus at the fifth and tenth vertebral segments of the tail to induce IVD degeneration. In each group, TGF-beta(1) immunoreactivity and morphometry of vertebral trabecular width and anterior and posterior ligament thickness were evaluated. Histologically, disorganisation and irregularity of collagen fibres was seen in the degenerated (operated) IVD. Increased TGF-beta(1) expression in multinuclear chondrocytes was also observed as was decreased vertebral trabecular width. Importantly, the reduction of trabecular width observed in the operated degenerated group was reversed after MEL administration (p<0.0001). Similarly, TGF-beta(1) expression in multinuclear chondrocytes was dramatically increased after exogenous MEL application. Thus, there was a regression in histopathological changes after MEL treatment, with disk appearances similar to those of the control group. Based on our findings, we suggest that MEL activates the recovery process in the degenerated IVD tissue, possibly by stimulating TGF-beta(1) activity. This is the first report investigating the involvement of the pineal hormone MEL in the repair of rat IVD.

Animals↗
PubMed1992

Nuclear degeneration and meiotic aberrations observed in human oocytes matured in vitro: analysis by light microscopy.

OBJECTIVE: To apply an improved air-dry procedure for the light microscopic identification of both degenerate and aberrant meiotic configurations in cultured human oocytes. MATERIAL AND DESIGN: Meiotically immature, normal appearing human oocytes retrieved after oophorectomy were placed into culture for 9 to 46 hours. Subsequently, oocytes were assessed morphologically and then air dried for light microscopic examination of chromatin configurations. MAIN OUTCOME MEASURES: Oocyte chromatin configurations were identified as normal, degenerate, or aberrant and then classified according to meiotic stage. Retrospective analyses were conducted to determine if [1] normal meiotic configurations were associated with morphologically viable oocytes and [2] degenerate or aberrant meiotic configurations were always associated with degenerate oocytes. In addition, for each meiotic stage, the proportion of oocytes exhibiting either degenerate or aberrant chromatin configurations was calculated. RESULTS: Of 101 oocyte chromatin configurations analyzed, 71.3% were normal, 11.9% were degenerate, and 16.8% displayed meiotic aberrations. Retrospective analyses revealed that the majority of both normal and aberrant chromatin configurations were associated with morphologically viable oocytes (93.1% and 88.2%, respectively), whereas all of the degenerate chromatin configurations were associated with morphologically degenerate oocytes. When assessed by stage, nuclear degeneration was observed exclusively at the germinal vesicle and diakinesis stages, whereas meiotic aberrations occurred most frequently after chromosome condensation. These aberrations were manifested either as clumped metaphase I configurations or as two distinct groups of bivalents that appeared to result from bivalent migration along the meiotic spindle without homologue segregation. CONCLUSIONS: Slightly > 25% of human oocytes recovered after oophorectomy were incapable of undergoing normal meiotic maturation in culture. The majority of these abnormal oocytes appeared morphologically normal and yet possessed meiotic aberrations. These observations indicate that caution should be taken when using oocytes matured in vitro for application in assisted reproductive technology programs.

Anaphase↗
PubMed1998

Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression.

Axial and radial specimens of non-degenerate and degenerate human anulus fibrosus (AF) were tested in confined compression to test the hypothesis that degeneration significantly affects the compressive properties of AF. Due to the highly oriented structure of AF, a secondary objective was to investigate anisotropic behaviors of AF in compression. Uniaxial swelling and stress relaxation experiments were performed on site-matched samples of anulus from the anterior outer region of L2-3 intervertebral discs. The experimental stress-relaxation behavior was modeled using the finite deformation biphasic theory and a finite-difference approximation scheme. Significant effects of degeneration but not orientation were detected for the reference stress offset, sigma(offset), and parameters describing the compressive stiffness (i.e. reference aggregate modulus, H(A0), and nonlinear stiffening coefficient, beta). Average values were 0.13+/-0.06 and 0.05+/-0.05 MPa for sigma(offset), 0.56+/-0.21 and 1.10+/-0.53 MPa for H(A0) and 2.13+/-1.48 and 0.44+/-0.61 for beta for all normal and degenerate specimens, respectively. No significant effect of degeneration or orientation were detected for either of the parameters describing the strain-dependent permeability (i.e. reference permeability, k0 and strain-dependent permeability coefficient, M) with average values for all specimens of 0.20+/-0.10 x 10(-15) m4/N-s and 1.18+/-1.30 for k0 and M, respectively. The loss of sigma(offset) was compensated with an elastic stiffening and change in the shape of the equilibrium stress-strain curve with H(A0) for degenerate tissues almost twice that of normal tissues and beta less than one sixth. The increase in reference elastic modulus with degeneration is likely related to an increase in tissue density resulting from the loss of water content. The significant effects of degeneration reported in this study suggested a shift in load carriage from fluid pressurization and swelling pressure to deformation of the solid matrix of the AF. The results also suggest that the highly organized and layered network of the anulus fibrosus, which gives rise to significant anisotropic effects in tension, does not play a major role in contributing to the magnitude of compressive stiffness or the mechanisms of fluid flow of the anulus in the confined compression configuration.

Adolescent↗
PubMed2000

Disc degeneration in patients with lumbar spondylolysis.

The grade of intervertebral disc degeneration in 73 symptomatic patients with lumbar spondylolysis was evaluated with magnetic resonance imaging to assess the prevalence of disc degeneration. The results were compared with those of age- and sex-matched asymptomatic control populations and with patients with clinical back pain symptoms but without spondylolysis. The relationship between disc degeneration and age of patients, the duration and severity of clinical symptoms, and the grade of vertebral slip was evaluated. A five-point grading scale based on T2 signal intensity recommended by Gibson et al. was used to evaluate the degree of disc degeneration. The grade of disc degeneration below the spondylolytic defect in the patients was highly significantly related to the age of patients (p < 0.01) and was more severe than in the controls (p < 0.01), but there was no difference of disc degeneration above the defect between the patients and the controls (p > 0.05). Furthermore, the grade of disc degeneration below the spondylolytic defect in the patients was highly significantly correlated with the duration of clinical symptoms (p < 0.01), although it was not associated with the severity of clinical symptoms or the grade of vertebral slip (p > 0.05). The results suggest that the degree of disc degeneration at the spondylolytic level is a more important determinant for choice of the fusion procedure than the age of the patients or the grade of vertebral slip, and that preoperative magnetic resonance examination is of great importance to evaluation of disc degeneration.

Adolescent↗
PubMed2002

Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during intervertebral disc degeneration.

STUDY DESIGN: This study correlates the mRNA and protein levels of large and small proteoglycans with the morphologic grade of degeneration. OBJECTIVES: To investigate changes in mRNA and protein levels of aggrecan, versican, biglycan, decorin and fibromodulin in the anulus fibrosus and the nucleus pulposus at different stages of tissue degeneration. SUMMARY OF BACKGROUND DATA: Proteoglycans are found in both the anulus fibrosus and nucleus pulposus and contribute to the hydration of the tissue (aggrecan) and the regulation of matrix assembly (small proteoglycans). Changes in their abundance may influence the biochemical and biomechanical properties of the disc and may have an effect on disc function. METHODS: Thirty-four human lumbar intervertebral discs were graded using Thompson's morphologic scale. The mRNA and protein content of aggrecan, versican, biglycan, decorin and fibromodulin was measured in extracts of anulus fibrosus and nucleus pulposus tissues dissected from these specimens. Protein levels were analyzed by Western blotting, and mRNA levels were semiquantified by reverse transcription polymerase chain reaction. RESULTS: In the anulus fibrosus, the mRNA and protein content of all proteoglycans was significantly elevated at early stages of degeneration then declined in severely degenerated tissues. In contrast, matrix components in the nucleus pulposus showed a continuous decrease in content with increasing grade of degeneration. CONCLUSIONS: Cells of the anulus fibrosus and nucleus pulposus react to tissue degeneration differently. Decreased mRNA expression by nucleus pulposus cells and declining protein content of the matrix make the nucleus more vulnerable to degeneration than the anulus. The cells in the anulus fibrosus respond to early degeneration by upregulating biosynthetic processes. However, in heavily degenerated tissues, the decline in the synthesis of aggrecan and the increase in the concentrations of small proteoglycans may be responsible for the failure of the repair processes.

Aggrecans↗
PubMed2004

Lumbar disc degeneration: epidemiology and genetic influences.

STUDY DESIGN: A literature review. OBJECTIVE: To synthesize the scientific literature on the prevalence of lumbar disc degeneration and factors associated with its occurrence, including genetic influences. METHODS: A literature review was conducted of the prevalence of disc degeneration. Studies of the etiology of disc degeneration were summarized, with particular attention given to studies of genetic influences. RESULTS AND CONCLUSIONS: There are extreme variations in the reported prevalence of specific degenerative findings of the lumbar spine among studies, which cannot be explained entirely by age or other identifiable risk factors (e.g., prevalence figures for disc narrowing varied from 3% to 56%). It is likely that these variations are due, in great part, to inconsistencies in case definitions and measurements, which are impeding epidemiologic research on disc degeneration. Research conducted over the past decade has led to a dramatic shift in the understanding of disc degeneration and its etiology. Previously, heavy physical loading was the main suspected risk factor for disc degeneration. However, results of exposure-discordant monozygotic and classic twin studies suggest that physical loading specific to occupation and sport has a relatively minor role in disc degeneration, beyond that of upright postures and routine activities of daily living. Recent research indicates that heredity has a dominant role in disc degeneration, explaining 74% of the variance in adult populations studied to date. Since 1998, genetic influences have been confirmed by the identification of several gene forms associated with disc degeneration.

Genetic Predisposition to Disease↗
PubMed2005

Disc degeneration in the rabbit: a biochemical and radiological comparison between four disc injury models.

STUDY DESIGN: A biochemical and radiologic comparison of 4 disc injury models to produce disc degeneration in the rabbit was carried out in 2 experiments. OBJECTIVES: To develop a reliable animal model of intervertebral disc degeneration. SUMMARY OF BACKGROUND DATA: In order to study various interventions for retarding or preventing disc degeneration, a reliable animal model of disc degeneration is needed. METHODS: First experiment: 7 New Zealand white rabbits (1 year old, 3.5-4.5 kg body weight) were used to test 4 different disc injury models; intradiscal injection of Camptothecin (an apoptotic agent) using a 23-gauge needle at L2-L3, nucleus aspiration using a 21-gauge needle at L3-L4, 3 anulus punctures using a 21-gauge needle at L4-L5, and 1 anulus puncture using a 18-gauge needle at L5-L6. The L1-L2 level was used as a control. Rabbits were killed 12 weeks later. Lumbar spinal magnetic resonance images were assessed using 4 grades of disc degeneration. The water content of the nucleus was measured. Dimethylmethylene blue (DMMB) assay was used to measure the sulfated-glycosaminoglycan content. Second experiment: the 21-gauge 3-puncture and the 18-gauge 1-puncture models, thought most effective in producing disc degeneration in the first experiment, were again used in a second study. Six rabbits were killed 8 weeks later, the water and sulfated-glycosaminoglycan contents being measured as in the first experiment. RESULTS: In the first experiment, the water content in the aspiration and puncture models was significantly decreased. Only the sulfated-glycosaminoglycan content in the aspiration model showed a significant decrease as compared to the control. Disc heights and magnetic resonance grades documented significant degeneration occurring in the aspiration and puncture models. In the second experiment, the water content showed a significant decrease in the 21-gauge 3-puncture model, whereas neither of the results for the sulfated-glycosaminoglycancontent showed a significant difference as compared to the control data. CONCLUSION: In the first experiment, the 21-gauge 3-puncture and the 18-gauge 1-puncture models produced the most consistent disc degeneration in the rabbit lumbar spine. When these 2 models were again studied in the second experiment, the 21-gauge 3-puncture technique was superior in producing disc degeneration over a shorter period of time.

Animals↗
PubMed2005

2004 Young Investigator Award Winner: vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration.

STUDY DESIGN: Intervertebral disc degeneration was evaluated by morphologic appearance, magnetic resonance imaging, and by biochemical matrix composition. Caliber and distribution of openings of the adjacent vertebral osseous endplates were measured. OBJECTIVES: Correlation between occlusion of vertebral endplate openings and intervertebral disc degeneration was quantified. SUMMARY OF BACKGROUND DATA: Calcifications of vertebral endplates with disease and age have suggested insufficient nutrition as a mechanism for intervertebral disc degeneration. It has been proposed that occlusion of endplate openings, which contain vascular sources for the disc, may limit the transport of nutrients, leading to disc degeneration. METHODS: Fresh magnetic resonance images from 39 human lumbar discs were scored. Sectioned discs with endplates were morphologically graded. Samples of nuclear and anular regions were evaluated for proteoglycan and collagen contents. Backlight microscopic images of 4 endplate regions were obtained, and caliber and distribution of endplate openings for each disc were measured. Analysis of variance regression models were used to assess correlation between endplate openings and disc degeneration. RESULTS: The decrease in opening density significantly correlated to morphologic degeneration grade, best for openings with 20 to 50 im equivalent diameter and in the nuclear region. Although the density of 20 to 50 im openings also significantly indirectly correlated to age, it was not as strong as the correlation to degeneration grade. Opening density was also significantly correlated to proteoglycan content in all regions. However, all other biochemical parameters as well as the T2 intensity score showed only weak or no correlation to opening density. CONCLUSIONS: A high indirect correlation between the density of openings in the osseous endplate (particularly of the size of the capillary buds) and the morphologic degeneration grade of the disc support the hypothesis that occlusion of these openings may deprive the cells of nutrients, leading to insufficient maintenance of the extracellular matrix and disc degeneration.

Adult↗
PubMed2005

Internal strains in healthy and degenerated lumbar intervertebral discs.

STUDY DESIGN: A biomechanical study investigating the intradiscal mechanics of human lumbar intervertebral discs (IVDs). OBJECTIVES: To assess the relationship between nucleus pulposus migration and intradiscal strains as a function of degeneration. SUMMARY OF BACKGROUND DATA: Intradiscal deformation studies have documented the nucleus pulposus migration capabilities during bending but without assessing subsequent intradiscal strains of the anulus fibrosus. Degenerated IVDs show higher anular laxity, hypermobility, and, perhaps, segmental instability. It is unknown if nucleus pulposus migration might be the cause of increased intradiscal anular strains and if such a phenomenon is modulated by IVD degeneration. METHODS: Eighteen healthy and degenerated IVDs were subjected to compression, extension, flexion, and lateral bending. Craniocaudal radiographs at unloaded and loaded steps documented positions of wires placed within and beads glued to the external surface in the mid-transverse plane. Circumferential and radial strains from the anterior, lateral, and posterolateral regions during load were compared between healthy and degenerated IVDs. RESULTS: The nucleus pulposus migrated to the opposite side of bending regardless of bending direction and significantly more in degenerated IVDs. The highest nucleus pulposus migration was observed during lateral bending. Circumferential tensile strains were significantly higher in the posterolateral regions of degenerative IVDs during all loads. Degeneration significantly increased radial tensile and compressive strains during all bending loads. CONCLUSIONS: Increased nucleus pulposus migration in degenerated IVDs may result in increased shifting of the IVD pivot point during bending movements as well as intradiscal anular strains, particularly in the posterolateral anulus. This phenomenon may explain the segmental instability observed in degenerated segments as well as the associated anular tears present in the posterolateral region before IVD failure.

Aged↗
PubMed2005

Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression.

STUDY DESIGN: The biphasic compressive material properties of normal and degenerate human nucleus pulposus tissue were measured in confined compression. OBJECTIVES: The objective of this study was to determine the effects of degeneration and age on the mechanical properties of human nucleus pulposus. SUMMARY OF BACKGROUND DATA: The nucleus pulposus exhibits swelling behavior in proportion to proteoglycan content. In shear, the nucleus exhibits both fluid-like and solid-like properties, suggesting a biphasic nature. To date, biphasic compressive properties of human nucleus pulpous have not been reported. METHODS: Human nucleus pulposus samples were tested in confined compression. Isometric swelling stress and effective aggregate modulus were measured. Linear biphasic theory was used to determine the permeability of the tissue. Mechanical behavior was correlated with proteoglycan and water content. RESULTS: Degeneration produced significant decreases in swelling stress (Psw = 0.138 +/- 0.029 MPa nondegenerate, Psw = 0.037 +/- 0.038 MPa degenerate) and effective aggregate modulus (H(A)(eff) = 1.01 +/- 0.43 MPa nondegenerate, H(A)(eff) = 0.44 +/- 0.19 MPa degenerate). Both properties were inversely correlated with proteoglycan content. Permeability increased with degeneration (ka = 0.9 +/- 0.43 x 10(-15) m4/N-s nondegenerate, ka = 1.4 +/- 0.58 x 10(-15) m4/N-s degenerate). CONCLUSIONS: Swelling is the primary load-bearing mechanism in both nondegenerate and degenerate nucleus pulposus. Knowledge of the biphasic material properties of the nucleus pulposus will aid the development of new treatment strategies for disc degeneration aimed at restoring mechanical function of the intervertebral disc.

Adult↗
PubMed2006

Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment.

Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD.

Adrenergic Agonists↗
PubMed2006

Biologic modification of animal models of intervertebral disc degeneration.

Intervertebral disc degeneration is a chronic process that can become manifest in clinical disorders such as idiopathic low back pain, sciatica, disc herniation, spinal stenosis, and myelopathy. The limited available treatment options (including discectomy and spinal fusion) for these and other disabling conditions that arise from intervertebral disc degeneration are highly invasive, achieve limited success, and only address acute symptoms while doing nothing to halt the process of degeneration. Although the precise pathophysiology of intervertebral disc degeneration has yet to be clearly delineated, the progressive decline in aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final common pathway. Animal models as well as in vitro studies of the process of disc degeneration have yielded many potentially useful targets for the reversal of disc degeneration. One current research trend is the use of established animal models of disc degeneration to study the role of therapeutic modalities in reversing the process of degeneration, often with use of the delivery of genes or gene products that influence the anabolic and catabolic pathways of the disc. This article reviews the ability of gene-product delivery systems and gene therapy to alter biologic processes in animal models of disc degeneration and examines future trends in this field.

Animals↗
PubMed2003

[Degenerate PCR and its application in gene cloning].

Degenerate PCR is introduced in this paper, including what is degenerate PCR, how to design degenerate primers, how to optimize degenerate PCR parameters, how to applying degenerate PCR to obtain full-length gene and which fields can apply degenerate PCR. The limits and recent advances of degenerate PCR are also discussed. Based on this introduction,strategies of gene cloning and applications of degenerate PCR in gene cloning are summarized in brief. Degenerate PCR is a very useful tool for searching and discovering new genes and new members of a protein family.

English Abstract↗