The influence of serum, glucose and oxygen on intervertebral disc cell growth in vitro:implications for degenerative disc disease

The avascular nature of the human intervertebral disc (IVD) is thought to play a major role in disc pathophysiology by limiting nutrient supply to resident IVD cells. In the human IVD, the central IVD cells at maturity are normally chondrocytic in phenotype. However, abnormal cell phenotypes have been associated with degenerative disc diseases, including cell proliferation and cluster formation, cell death, stellate morphologies, and cell senescence. Therefore, we have examined the relative influence of possible blood-borne factors on the growth characteristics of IVD cells in vitro.

Experimental procedures for the identification of material properties of intervertebal disc - a contribution for the development of biomimetic substitutes for the nucleus pulposus

Tese de Doutoramento em Engenharia Mecânica.

Disc degeneration: current surgical options.

Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

A retrospective study of the epidemiological and clinic-pathological aspects of cattle and buffaloes with degenerative joint disease (DJD) was conducted in the state of Pará, Brazil. From 1999 to 2014, eleven cattle and 24 buffaloes were evaluated. All the treated animals with suspected DJD underwent a clinical examination of the musculoskeletal system. In seven cattle and eight buffaloes with clinical signs of the disease postmortem examination was performed. The common clinical signs observed in both species were chronic lameness, stiff gait, postural changes, audible crackles in the affected limb, prolonged recumbency, difficulty in getting up and progressive weight loss. The lesions observed at necropsy were: irregular articular surfaces, erosion of the articular cartilage and the underlying bone tissue, and proliferation of the periarticular bone tissue with formation of osteophytes. The most affected joints in cattle and buffaloes wereof the hind limb. In buffaloes, the main predisposing factor to the onset of DJD was phosphorus deficiency. In cattle, defects of the anatomical conformation of the hind limbs, chronic trauma due to the activities performed, such as semen collection, and advanced age possibly contributed to the emergence of the disease.

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

Foi realizado um estudo retrospectivo sobre os aspectos epidemiológicos e clínico-patológicos em bovinos e búfalos com doença articular degenerativa (DAD) no estado do Pará, Brasil. Durante os anos de 1999 a 2014 foram avaliados 11 bovinos e 24 bubalinos. Todos os animais atendidos com suspeita clínica de DAD foram submetidos a exame clínico do sistema locomotor. Foram necropsiados sete bovinos e oito bubalinos com sinais clínicos da enfermidade. Os sinais clínicos comuns observados em ambas as espécies foram claudicação crônica, andar rígido, alterações posturais, crepitações audíveis no membro acometido, decúbito prolongado, dificuldade para levantar, e emagrecimento progressivo. As lesões articulares evidenciadas na necropsia consistiram em irregularidade da superfície articular, presença de erosão na cartilagem articular e no tecido ósseo subjacente, proliferação de tecido ósseo periarticular com formação de osteófitos. Tanto nos bovinos como nos bubalinos as articulações mais acometidas foram as dos membros posteriores. Nos bubalinos, possivelmente o principal fator predisponente ao surgimento de DAD foi à deficiência de fósforo, ao contrário dos bovinos, nos quais os defeitos de conformação anatômica dos membros posteriores, traumas crônicos em virtude da atividade exercida, como a coleta de sêmen e a idade avançada, foram o que, possivelmente, contribuíram para surgimento da enfermidade.

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Detection of degenerative cartilage disease: comparison of high-resolution morphological MR and quantitative T2 mapping at 3.0 Tesla

The aim of the study was to investigate the association of T2 relaxation times of the knee with early degenerative cartilage changes. Furthermore the impact of unloading the knee on T2 values was evaluated.

Incidence of spinal compressive lesions in chondrodystrophic dogs with abnormal recovery after hemilaminectomy for treatment of thoracolumbar disc disease: a prospective magnetic resonance imaging study

OBJECTIVE: To investigate causes of the lack of clinical improvement after thoracolumbar disc surgery. STUDY DESIGN: Case-control magnetic resonance imaging (MRI) study. ANIMALS: Chondrodystrophic dogs with acute thoracolumbar disc disease treated by hemilaminectomy: 10 that had no short-term clinical improvement and 12 with "normal" clinical improvement. METHODS: Dogs that had surgery for treatment of intervertebral disc extrusion (2003-2008) where thoracolumbar disc disease was confirmed by MRI were evaluated to identify dogs that had lack of clinical improvement after surgery. Ten dogs with delayed recovery or clinical deterioration were reexamined with MRI and compared with 12 dogs with normal recovery and MRI reexamination after 6 weeks (control group). RESULTS: Of 173 dogs, 10 (5.8%) had clinical deterioration within 1-10 days after surgery. In 8 dogs, residual spinal cord compression was identified on MRI. Bleeding was present in 1 dog. In 3 dogs, the cause was an incorrect approach and insufficient disc material removal. In 3 dogs, recurrence occurred at the surgical site. In 1 dog, the centrally located extruded material was shifted to the contralateral side during surgery. These 8 dogs had repeat surgery and recovery was uneventful. In 2 dogs, deterioration could not be associated with a compressive disc lesion. Hemorrhagic myelomalacia was confirmed by pathologic examination in 1 dog. The other dog recovered after 6 months of conservative management. CONCLUSION: Delayed postsurgical recovery or deterioration is commonly associated with newly developed and/or remaining compressive disc lesion. CLINICAL RELEVANCE: We recommend early MRI reexamination to assess the postsurgical spinal canal and cord, and to plan further therapeutic measures in chondrodystrophic dogs with delayed recovery after decompressive hemilaminectomy for thoracolumbar disc disease.

Axial T2 mapping in intervertebral discs: a new technique for assessment of intervertebral disc degeneration

To demonstrate the potential benefits of biochemical axial T2 mapping of intervertebral discs (IVDs) regarding the detection and grading of early stages of degenerative disc disease using 1.5-Tesla magnetic resonance imaging (MRI) in a clinical setting.

Cartilage tissue engineering for degenerative joint disease

Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed.

Influence of diurnal hyperosmotic loading on the metabolism and matrix gene expression of a whole-organ intervertebral disc model

It is generally agreed that the mechanical environment of intervertebral disc cells plays an important role in maintaining a balanced matrix metabolism. The precise mechanism by which the signals are transduced into the cells is poorly understood. Osmotic changes in the extracellular matrix (ECM) are thought to be involved. Current in-vitro studies on this topic are mostly short-term and show conflicting data on the reaction of disc cells subjected to osmotic changes which is partially due to the heterogenous and often substantially-reduced culture systems. The aim of the study was therefore to investigate the effects of cyclic osmotic loading for 4 weeks on metabolism and matrix gene expression in a full-organ intervertebral disc culture system. Intervertebral disc/endplate units were isolated from New Zealand White Rabbits and cultured either in iso-osmotic media (335 mosmol/kg) or were diurnally exposed for 8 hours to hyper-osmotic conditions (485 mosmol/kg). Cell viability, metabolic activity, matrix composition and matrix gene expression profile (collagen types I/II and aggrecan) were monitored using Live/Dead cell viability assay, tetrazolium reduction test (WST 8), proteoglycan and DNA quantification assays and quantitative PCR. The results show that diurnal osmotic stimulation did not have significant effects on proteoglycan content, cellularity and disc cell viability after 28 days in culture. However, hyperosmolarity caused increased cell death in the early culture phase and counteracted up-regulation of type I collagen gene expression in nucleus and annulus cells. Moreover, the initially decreased cellular dehydrogenase activity recovered with osmotic stimulation after 4 weeks and aggrecan gene down-regulation was delayed, although the latter was not significant according to our statistical criteria. In contrast, collagen type II did not respond to the osmotic changes and was down-regulated in both groups. In conclusion, diurnal hyper-osmotic stimulation of a whole-organ disc/endplate culture partially inhibits a matrix gene expression profile as encountered in degenerative disc disease and counteracts cellular metabolic hypo-activity.

Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era

The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time.

Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease

The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases.

Influence of intervertebral disc fenestration at the herniation site in association with hemilaminectomy on recurrence in chondrodystrophic dogs with thoracolumbar disc disease: a prospective MRI study

OBJECTIVE To describe the influence of fenestration at the disc herniation site on recurrence in thoracolumbar disc disease of chondrodystrophoid dogs. STUDY DESIGN Prospective clinical study. ANIMALS Chondrodystrophic dogs (n=19). METHODS Dogs were divided into 2 groups: group 1 (9 dogs) had thoracolumbar disc extrusion (Hansen type I) treated by hemilaminectomy and concomitant fenestration of the affected intervertebral disc and group 2 (10 dogs) had hemilaminectomy without fenestration. All dogs had 3 magnetic resonance imaging (MRI) examinations: preoperatively, immediately postoperatively to assess removal of herniated disc material, and again 6 weeks after surgery. RESULTS There were 13 male and 6 female dogs; mean age, 7.1 years. Thoracolumbar disc herniation was confirmed with MRI. Immediate post surgical MRI revealed that the herniated disc removal was complete in all but 1 dog and that fenestration did not lead to complete removal of nucleus pulposus within the intervertebral disc space. On the 3rd MRI examination, none of the group 1 dogs had further disc material herniation at the fenestrated site. Six of the 10 group 2 dogs had a recurrence of herniation leading to clinical signs in 3 dogs (pain in 2 dogs, paresis in 1 dog). CONCLUSION In thoracolumbar disc herniation, fenestration of the affected intervertebral disc space prevents further extrusion of disc material. CLINICAL RELEVANCE Fenestration reduces the risk of early recurrence of disc herniation and associated postoperative complications.