ascorbic-acid and Osteoarthritis

Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.

Topics: Aged; Alkaptonuria; Ascorbic Acid; Cartilage Diseases; Dioxygenases; Homogentisic Acid; Humans; Joint Diseases; Ochronosis; Osteoarthritis; Quality of Life; Spondylarthropathies; Tyrosine

The successful use of rose hip for the treatment of osteoarthritis is well documented. Several randomized placebo controlled double-blind studies, as mono or combination therapy, have demonstrated treatment efficacy as well as excellent tolerability.. This review focuses on the molecular mechanism underlying the clinical effects of rose hip in osteoarthritis (OA).. The database Medline was screened - using the search term "Rosa canina" or "rose hip" - for publications on pharmacological or mechanistic studies with relevance to OA; in addition for findings on pharmacologically active constituents as well as clinical studies. The screening results were complemented by following-up on cited literature.. In particular, 24 pharmacological studies on Rosa canina or preparations thereof were considered relevant. Potent antioxidant radical scavenging effects are well documented for numerous rose hip constituents besides Vitamin C. Furthermore, anti-inflammatory activities include the reduction of pro-inflammatory cytokines and chemokines, reduction of NF-kB signaling, inhibition of pro-inflammatory enzymes, including COX1/2, 5-LOX and iNOS, reduction of C-reactive protein levels, reduction of chemotaxis and chemoluminescence of PMNs, and an inhibition of pro-inflammatory metalloproteases.. The antioxidant and anti-inflammatory effects of Rosa canina match its clinical action - especially considering new findings on the pharmacological disease pattern of OA. The entirety of several compounds including phenolics, terpenoids, galactolipids, carotenoids, fruit acids and fatty oils can be considered responsible for the observed pharmacological and clinical effects. Further research is needed to eludicate how and in which manner single rose hip compounds interact with their molecular pharmacological targets.

Topics: Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Chemokines; Cytokines; Double-Blind Method; Free Radical Scavengers; Fruit; Humans; NF-kappa B; Osteoarthritis; Plant Extracts; Randomized Controlled Trials as Topic; Rosa; Treatment Outcome

Osteoarthritis (OA) treatment is limited by the inability of prescribed medications to alter disease outcome. As a result, patients with OA often take food substances called nutraceuticals in an attempt to affect the structural changes that occur within a degenerating joint. The role of nutraceuticals in OA management can be defined only by an evidence-based approach to support their use. This paper reviews the clinical trials studying glucosamine, chondroitin sulfate, vitamin C, vitamin E, and avocado-soybean unsaponifiables. It highlights the need for additional randomized, placebo-controlled trials to further define the utility of nutraceuticals in OA treatment.

Topics: Ascorbic Acid; Cartilage, Articular; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Glycine max; Humans; Osteoarthritis; Persea; Plant Extracts; Randomized Controlled Trials as Topic; Vitamin E

Despite the recognition that degenerative cartilage disorders like osteoarthritis (OA) and osteochondritis dissecans (OCD) may have nutritional abnormalities at the root of their pathogenesis, balanced dietary supplementation programs have played a secondary role in their management. This review emphasizes the importance and role of nutritional factors such as glucose and glucose-derived sugars (i.e. glucosamine sulfate and vitamin C) in the development, maintenance, repair, and remodeling of cartilage. Chondrocytes, the cells of cartilage, consume glucose as a primary substrate for ATP production in glycolysis and utilize glucosamine sulfate and other sulfated sugars as structural components for extracellular matrix synthesis and are dependent on hexose uptake and delivery to metabolic and biosynthetic pools. Data from several laboratories suggests that chondrocytes express multiple isoforms of the GLUT/SLC2A family of glucose/polyol transporters. These facilitative glucose transporter proteins are expressed in a tissue and cell-specific manner, exhibit distinct kinetic properties, and are developmentally regulated. They may also be regulated by endocrine factors like insulin and insulin-like growth factor I (IGF-I) and cytokines such as interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha). Recent studies suggest that degeneration of cartilage may be triggered by metabolic disorders of glucose balance and that OA occurs coincident with metabolic disease, endocrine dysfunction and diabetes mellitus. Based on these metabolic, endocrine and developmental considerations we present a novel hypothesis regarding the role of glucose transport and metabolism in cartilage physiology and pathophysiology and speculate that supplementation with sugar-derived vitamins and nutraceuticals may benefit patients with degenerative joint disorders.

Topics: Animals; Ascorbic Acid; Bone and Bones; Bone Development; Cartilage; Cartilage, Articular; Chondrocytes; Chondrogenesis; Endocrine Glands; Glucose; Humans; Monosaccharide Transport Proteins; Nutritional Physiological Phenomena; Osteoarthritis; Regional Blood Flow

There are at least four mechanisms whereby the nutrient vitamins A, C, D, and E may be related to the processes that impede or give rise to OA. These nutrient vitamins have major roles in modulating oxidative stress, participating in immune responses, and contributing to cell differentiation. There is a substantial need to understand the contribution of these nutrients to OA, because they may provide important insight into ameliorating the initiation and progression of the disease. Simultaneously, greater understanding will add rationality to an area of potential intervention that is often based on anecdote. Investigation will be complex; there is the need to select appropriate systems. Typical animal model systems used in the study of OA are inappropriate because most animals can synthesize ascorbic acid. There is the need to disaggregate, as much as possible, the numerous subsets of OA and the plethora of processes that contribute to that heterogeneity. Certainly, there is the need to recognize the interdependency of the actions of each of these nutrients at the cellular level. Furthermore, humans rarely consume these nutrients as independent products. For example, watermelon is a primary source of both ascorbic acid and beta-carotene. Failure to address these complexities denies the scientist the opportunity to advance our understanding of health and disease processes. More importantly, failure to address these complexities denies the person with OA the opportunity to address his or her own health.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Humans; Osteoarthritis; Vitamin A; Vitamin D; Vitamin E

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Carbazoles; Chondroitin Sulfates; Chronic Disease; Dog Diseases; Dogs; Double-Blind Method; Gait; Glucosamine; Lameness, Animal; Manganese Compounds; Meloxicam; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Stifle; Thiazines; Thiazoles; Treatment Outcome

The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on aging-associated skin changes and backache and joint pain was tested in a case-controlled study of 40 test subjects and 40 age-matched control subjects (mean age, 65 years) complaining of backache and knee joint pain due to osteoarthritis, spondylosis deformans, and/or osteoporosis. Supplementation with 900 mg calcium (given as AAA Ca) and 3.5 g collagen and other matrix components, including glucosamine, daily for 4 months resulted in a marked alleviation of subjective pain, assessed by the face scale. A fall of skin impedance in response to exercise loads, such as standing up, walking, squatting, and climbing up and down stairs, reported as an objective manifestion of pain, was also alleviated. The basal skin impedance, which increases with age, was significantly reduced in response to the Ca-collagen-matrix supplementation, suggesting a change of skin properties similar to rejuvenation, along with subjective smoothening and moistening of the skin. Urinary excretion of N-terminal crosslinking telopeptide of type I collagen (NTx) was decreased in the Ca-collagen-matrix supplementation group, but not in the control group. In addition to calcium suppression of parathyroid hormone, preventing bone resorption, collagen, acting on the intestinal lymphatic system, may protect collagen from degradation through the inhibition of cytokine-induced release of metalloproteinases, including collagenase.

Topics: Absorption; Aged; Ascorbic Acid; Bone Density; Calcium; Case-Control Studies; Collagen; Collagen Type I; Electric Impedance; Extracellular Matrix; Female; Glucosamine; Glycosaminoglycans; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Osteoarthritis; Osteoporosis; Pain; Peptides; Skin Physiological Phenomena

A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted.. Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score.. Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects.. The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.

Topics: Activities of Daily Living; Adult; Ascorbic Acid; Chondroitin Sulfates; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Combinations; Glucosamine; Humans; Lumbar Vertebrae; Male; Manganese Compounds; Middle Aged; Military Personnel; Naval Medicine; Osteoarthritis; Osteoarthritis, Knee; Pain; Pilot Projects; Radiography; Running; Surveys and Questionnaires

Selenium-ACE, a formulation containing the trace element selenium with three vitamins, is widely promoted for the treatment of arthritis. A controlled double-blind trial of Selenium-ACE in osteoarthritis failed to demonstrate any significant efficacy for the compound over placebo at 3 or 6 months though there was a non-significant trend to improvement in some clinical parameters in both groups. Side-effects were more frequently seen in the placebo group.

Topics: Adult; Aged; Ascorbic Acid; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Movement; Osteoarthritis; Pain; Random Allocation; Selenium; Time Factors; Vitamin A; Vitamin E

Topics: Animals; Ascorbic Acid; Cartilage; Cartilage, Articular; Chondrogenesis; Dexamethasone; Humans; Magnetic Phenomena; Mice; Osteoarthritis

Oxidative stress might play an important role in the development of osteoarthritis, but not much is known about the effect of antioxidants on osteoarthritis risk. We, therefore, aimed to investigate the effect of dietary vitamin C, E, beta-carotene, and non-enzymatic antioxidant capacity (NEAC), which measures overall antioxidant activity from the diet, on the risk of osteoarthritis.. For this study 43,865 men and women from the Swedish National March Cohort (SNMC) were followed for up to 19 years. We computed dietary intake of vitamin C, E and beta-carotene using information from a Food Frequency Questionnaire (FFQ). To estimate dietary NEAC we combined the information from the FFQ with food item-specific antioxidant capacity values from an antioxidant food database. Cases of osteoarthritis were identified through the Swedish National Patient Registers. We categorized all exposure variables into sex-specific quartiles and used multivariable-adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs).. In total, we observed 5976 cases of OA during 469,148 person-years of follow-up. After adjusting for potential confounders, we did not find any association between vitamin C, beta-carotene and NEAC (p-values for trend > 0.5), but a positive association was found with higher dietary vitamin E intake (HR Q4 vs Q1: 1.11; 95% CI 1.02-1.21; p for trend = 0.01) and the risk of OA.. Our findings do not provide evidence for dietary antioxidants to protect from the development of OA, and a higher dietary vitamin E intake might even increase the risk.

Topics: Antioxidants; Ascorbic Acid; Diet; Female; Humans; Male; Osteoarthritis; Risk Factors; Sweden

Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis.. Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed.. Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group.. In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.

Topics: Animals; Ascorbic Acid; Body Weight; Boswellia; Chondroitin Sulfates; Dogs; Fatty Acids, Omega-6; Female; Glucosamine; Male; Osteoarthritis; Plant Extracts; Triterpenes; Vitamin E

This study aimed to investigate the role of endothelin-1 (ET-1), originally known as the potent vasoconstrictor, and its receptors in chondrocyte senescence and osteoarthritis (OA) development.. Temporal changes of ET-1 and its receptors with OA development were characterized in a posttraumatic OA (PTOA) mouse model at time zero, 1-month and 4-month after surgical induction via destabilization of medial meniscus (DMM). A transgenic ET-1 overexpression (TET-1) mouse model was deployed to assess the impact of upregulated ET-1 on chondrocyte senescence and cartilage degradation. Effects of endothelin receptor blockade on chondrocyte senescence and OA development were further examined both in vitro and in vivo.. Local expression of ET-1 in subchondral bone and synovium upregulated after DMM with an increase of plasma ET-1 level from 3.18 ± 0.21 pg/ml at time zero to 6.47 ± 0.34 pg/ml at 4-month post-surgery. Meanwhile, endothelin type B receptor (ET. ET-1 could induce chondrocytes senescence and cartilage damages via ET

Topics: Animals; Antioxidants; Ascorbic Acid; Cartilage, Articular; Cellular Senescence; Chondrocytes; Cyclin-Dependent Kinase Inhibitor p16; Disease Models, Animal; Endothelin-1; Mice, Transgenic; Osteoarthritis; Receptors, Endothelin; Up-Regulation

Osteoarthritis (OA) is one of the most common degenerative diseases especially in the knee joint. The definitive method for the treatment of this disease is not known. In recent years, use of platelet-derived products has been considered as a new therapeutic approach because of its low cost, easy to use, and minimum side effects. Serum rich of growth factors (SRGF) is one of the biological compounds used to healing and regeneration. Its effects may improve in combination with antioxidants such as vitamin C. This vitamin increases the synthesis of proteoglycans by chondrocytes. The present study investigated effect of xenogenous SRGF in combination with vitamin C on the monosodium iodoacetate-induction osteoarthritis in rats.. Animals were randomly categorized into three groups including OA, SRGF, and vitamin C+SRGF. Treatments were performed with 3 time intra-articular injection in weekly intervals. Knee samples were taken after two weeks of the last treatment for histopathologic investigations.. In the OA group, surface fibrillation and irregularity, multiple clefts, loss of chondrocytes, proteoglycan depletion with Toluidine blue staining were detected. In the treated group with SRGF/vitamin C, the severity of degenerative lesions was decreased. Chondrocytes had proliferated and matrix proteoglycan increased in compared to the SRGF and OA groups. Also, osteoarthritis stage was markedly reduced in this group rather than two other groups.. The results of this study show the synergic effect of vitamin C and growth factors on accelerating articular repair.

Topics: Animals; Ascorbic Acid; Cartilage, Articular; Chondrocytes; Disease Models, Animal; Injections, Intra-Articular; Intercellular Signaling Peptides and Proteins; Iodoacetic Acid; Knee Joint; Male; Osteoarthritis; Proteoglycans; Random Allocation; Rats; Rats, Wistar

Proinflammatory cytokines and reactive oxygen species (ROS) are known to be involved in the initiation and progression of osteoarthritis (OA). New evidence clarifying the correlation between ROS and inflammation has indicated that oxidative stress can up-regulate inflammatory cytokines. l-Ascorbic acid (AA), an antioxidant, has been shown to have anti-inflammatory effects and improve matrix deposition in chondrocytes. The purpose of this study was to examine the effects of hyaluronic acid (HA; 100 μg/mL) supplemented with AA (50 μg/mL) on human normal and interleukin-1 beta-stimulated (IL-1β, 10 ng/mL) chondrocytes. HA, AA, and HA + AA treatment did not change cell morphology, viability, proliferation, and glycosaminoglycan production in normal chondrocytes. HA, AA, and HA + AA, by contrast, partially restored viability and morphology of hypertrophic chondrocytes, and HA and HA + AA further decreased the cytotoxicity of IL-1β. Real-time PCR revealed that AA and HA + AA had no substantial effects on unstimulated chondrocytes, except for down-regulation of matrix metalloproteinase (MMP)-9 mRNA levels. For IL-1β-stimulated chondrocytes, significant down-regulation of IL-1β, tumor necrosis factor-alpha (TNF-α), MMP-3, and MMP-9 mRNA expression was found when cells were cultured in HA-supplemented media. Moreover, HA + AA supplementation further significantly decreased MMP-3 and MMP-9 mRNA expression. The protein production of MMP-3 was decreased, with a significant difference between the HA + AA group and HA group. The antioxidant capacity and superoxide dismutases activity were also partially restored in stimulated chondrocytes. HA supplemented with AA modulates MMPs expression and antioxidant fuction in chondrocytes. AA may enhance the anticatabolic effects of HA on OA chondrocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1809-1817, 2018.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Chondrocytes; Drug Synergism; Female; Gene Expression Regulation, Enzymologic; Humans; Hyaluronic Acid; Male; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Middle Aged; Osteoarthritis; Tumor Necrosis Factor-alpha

The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in cultured OB. Expanded cells continued to express differentiated OB markers independently of AA supplementation and demonstrated no changes in their capacity to osteogenically differentiate. Transcriptomic analyses revealed that apoptotic, cell cycle-proliferation, and catabolic pathways were the main pathways affected in the presence of AA during OB expansion. Supplementation with AA can thus help to expand subchondral bone OB in vitro while maintaining their special cellular characteristics. The clearance of such senescent OB could be envisioned as a potential therapeutic target for the treatment of OA.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cell Proliferation; Cells, Cultured; Cellular Senescence; Female; Humans; Male; Middle Aged; Osteoarthritis; Osteoblasts; Reactive Oxygen Species; Transcriptome; Vitamins

Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of vitamin C relates to a reduction in cartilage loss and OA. This study examined the efficacy of vitamin C to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the in vivo monosodium iodoacetate (MIA)-induced OA rat. Results demonstrated that, in SW1353 cells, treatment with 5 μM MIA inhibited cell growth and increased oxidative stress, apoptosis, and proteoglycan loss. In addition, the expression levels of the pro-inflammatory cytokines IL-6, IL-17A, and TNF-α and matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP-13 were increased. All of these MIA-induced changes could be prevented with treatment of 100 μM vitamin C. In an animal model, intra-articular injection of MIA-induced cartilage degradation resembled the pathological changes of OA, and treatment of vitamin C could lessen these changes. Unexpectedly, vitamin C's effects did not strengthen with the increasing dosage, while the 100 mg/kg dosage was more efficient than the 200 or 300 mg/kg dosages. Vitamin C possessed multiple capacities for prevention of OA progress, including a decrease in apoptosis and in the expression of pro-inflammatory cytokines and MMPs in addition to the well-known antioxidation.

Topics: Animals; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Chondrocytes; Cytokines; Humans; Iodoacetic Acid; Male; Matrix Metalloproteinases; Osteoarthritis; Oxidative Stress; Proteoglycans; Rats; Rats, Wistar; Vitamins

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Dietary Fiber; Exercise; Health Behavior; Health Status; Humans; Osteoarthritis; Quality of Life; Self Care

Patients with trapeziometacarpal joint arthritis stage II or III (according to Dell) and no benefit from non-operative therapy were selected to undergo joint arthroplasty. We performed 32 arthroplasties for first carpometacarpal arthritis in 27 patients using a cementless total trapeziometacarpal joint prosthesis. We undertook a prospective cohort study and evaluated the clinical results of total joint arthroplasty after an average of 39 months. Visual analogue scale (VAS) scores for pain, daily activities (ADL) and satisfaction were taken pre- and postoperatively, and the first web opening was measured. First web opening improved significantly as did pain, ADL and patient satisfaction. Surgery of arthritis of the first carpometacarpal joint can be complicated by complex regional pain syndrome (CRPS) type I. In all our patients Vitamin C 500 mg daily was started two days before surgery and continued during 50 days. There were no cases of CRPS under vitamin C prophylaxis. These results justify further investigation in a randomised clinical trial.

Topics: Arthroplasty; Ascorbic Acid; Complex Regional Pain Syndromes; Female; Humans; Male; Metacarpal Bones; Metacarpophalangeal Joint; Osteoarthritis; Prospective Studies; Trapezoid Bone; Treatment Outcome

The exact pro-oxidant and antioxidant status in osteoarthritis patients is still not clear. To add a new insight to the question, changes in the erythrocyte lipid peroxidation products (MDA), levels of glutathione (GSH), ascorbic acid and plasma vitamin E (nonenzymatic antioxidant parameters); and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase in erythrocytes and plasma glutathione - S - transferase (GST) were measured in patients with osteoarthritis.. This work was undertaken to assess oxidative stress and antioxidant status in patients with osteoarthritis.. The study was conducted in 20 patients and compared to controls. Levels of erythrocyte MDA, GSH, ascorbic acid, plasma vitamin E; and activities of antioxidant enzymes were measured in patients with osteoarthritis.. Erythrocyte GSH was measured by the method of Beutler et al. Ascorbic acid levels were measured by the method of Tietz. Plasma vitamin E levels were measured by the method of Baker et al. MDA was determined as the measure of thio barbituric acid reactive substances (TBARS). SOD activity in the hemolysate was measured by the method of Misra and Fridovich. Activity of catalase was measured by the method of Beers and Sizer. GPX activity was measured as described by Paglia and Valentine in erythrocytes and Plasma GST activity was measured as described by Warholm et al. These parameters were measured in 20 patients and compared to controls.. Statistical analysis between group 1 (controls) and group 2 (patients) was performed by the student's t - test using the stat -view package.. It was observed that there was a significant increase in erythrocyte MDA levels; SOD, GPX and plasma GST activities; and a significant decrease in erythrocyte GSH, ascorbic acid, plasma vitamin E levels and catalase activity in patients with osteoarthritis when compared to controls.. The results of our study suggest higher oxygen-free radical production, evidenced by increased MDA and decreased GSH, ascorbic acid, vitamin E and catalase activity, support to the oxidative stress in osteoarthritis. The increased activities of antioxidant enzymes may be a compensatory regulation in response to increased oxidative stress.

Topics: Adult; Antioxidants; Ascorbic Acid; Case-Control Studies; Female; Glutathione Peroxidase; Glutathione Transferase; Humans; Lipid Peroxidation; Male; Middle Aged; Osteoarthritis; Oxidative Stress; Superoxide Dismutase; Vitamin E

Osteoarthritis (OA) is a degenerative disease that disrupts the collagenous matrix of articular cartilage and is difficult to cure because articular cartilage is a nonvascular tissue. Treatment of OA has targeted macromolecular substitutes for cartilage components, such as hyaluronic acid or genetically engineered materials. However, the goal of the present study was to examine whether intra-articular injection of the elementary nutrients restores the matrix of arthritic knee joints in mature animals. A nutritive mixture solution (NMS) was composed of elementary nutrients such as glucose or dextrose, amino acids and ascorbic acid. It was administered five times (at weeks 6, 8, 10, 13 and 16) into the unilateral anterior cruciate ligament transected knee joints of mature New Zealand White rabbits, and the effect of NMS injection was compared with that of normal saline. OA progression was histopathologically evaluated by haematoxylin and eosin staining, by the Mankin grading method and by scanning electron microscopy at week 19. NMS injection decreased progressive erosion of articular cartilage overall compared with injection of normal saline (P < 0.01), and nms joints exhibited no differences relative to normal cartilage that had not undergone transection of the anterior cruciate ligament, as assessed using the mankin grading method. Haematoxylin and eosin staining and scanning electron microscopy findings also indicated that nms injection, in contrast to normal saline injection, restored the cartilage matrix, which is known to be composed of a collagen and proteoglycan network. thus, nms injection is a potent treatment that significantly retards oa progression, which in turn prevents progressive destruction of joints and functional loss in mature animals.

Topics: Age Factors; Amino Acids; Animals; Anterior Cruciate Ligament Injuries; Ascorbic Acid; Cartilage, Articular; Disease Progression; Female; Food; Glucose; Injections, Intra-Articular; Osteoarthritis; Pharmaceutical Solutions; Rabbits; Random Allocation

Datasets resulting from metabolomics or metabolic profiling experiments are becoming increasingly complex. Such datasets may contain underlying factors, such as time (time-resolved or longitudinal measurements), doses or combinations thereof. Currently used biostatistics methods do not take the structure of such complex datasets into account. However, incorporating this structure into the data analysis is important for understanding the biological information in these datasets.. We describe ASCA, a new method that can deal with complex multivariate datasets containing an underlying experimental design, such as metabolomics datasets. It is a direct generalization of analysis of variance (ANOVA) for univariate data to the multivariate case. The method allows for easy interpretation of the variation induced by the different factors of the design. The method is illustrated with a dataset from a metabolomics experiment with time and dose factors.

Topics: Algorithms; Analysis of Variance; Animals; Ascorbic Acid; Biomarkers; Computer Simulation; Dose-Response Relationship, Drug; Energy Metabolism; Gene Expression Profiling; Guinea Pigs; Male; Models, Biological; Models, Statistical; Multivariate Analysis; Osteoarthritis; Proteome; Software; Treatment Outcome

Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the identification of biomarkers. A metabolic fingerprint consists of a typical combination of metabolites in a biological fluid and is identified by a combination of (1)H NMR spectroscopy and multivariate data analysis (MVDA). The current feasibility study was aimed at identifying a metabolic fingerprint for OA and applying this in a nutritional intervention study. Urine samples were collected from osteoarthritic male Hartley guinea pigs (n = 44) at 10 and 12 mo of age, treated from 4 mo onward with variable vitamin C doses (2.5-3, 30 and 150 mg/d) and from healthy male Strain 13 guinea pigs (n = 8) at 12 mo of age, treated with 30 mg vitamin C/d. NMR measurements were performed on all urine samples. Subsequently, MVDA was carried out on the data obtained using NMR. An NMR fingerprint was identified that reflected the osteoarthritic changes in guinea pigs. The metabolites that comprised the fingerprint indicate that energy and purine metabolism are of major importance in OA. Metabolic fingerprinting also allowed detection of differences in OA-specific metabolites induced by different dietary vitamin C intakes. This study demonstrates the feasibility of metabolic fingerprinting to identify disease-specific profiles of urinary metabolites. NMR fingerprinting is a promising means of identifying new disease markers and of gaining fresh insights into the pathophysiology of disease.

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Diet; Dose-Response Relationship, Drug; Energy Metabolism; Guinea Pigs; Magnetic Resonance Spectroscopy; Male; Multivariate Analysis; Osteoarthritis; Peptide Mapping; Purines; Treatment Outcome

Reactive oxygen species (ROS) are implicated in both cartilage aging and the pathogenesis of osteoarthritis. We developed an in vitro model to study the role of chondrocyte-derived ROS in cartilage matrix protein degradation. Matrix proteins in cultured primary articular chondrocytes were labeled with [(3)H]proline, and the washed cell matrix was returned to a serum-free balanced salt solution. Exposure to hydrogen peroxide resulted in oxidative damage to the cell matrix as established by monitoring the release of labeled material into the medium. Calcium ionophore treatment of chondrocytes, in a dose-dependent manner, significantly enhanced the release of labeled matrix, suggesting a chondrocyte-dependent mechanism of matrix degradation. Antioxidant enzymes such as catalase or superoxide dismutase did not influence matrix release by the calcium ionophore-activated chondrocytes. However, vitamin E, at physiological concentrations, significantly diminished the release of labeled matrix by activated chondrocytes. The fact that vitamin E is a chain-breaking antioxidant indicates that the mechanism of matrix degradation and release is mediated by the lipid peroxidation process. Lipid peroxidation was measured in chondrocytes loaded with cis-parinaric acid. Both resting and activated cells showed constitutive and enhanced levels of lipid peroxidation activity, which were significantly reduced in the presence of vitamin E. In an immunoblot analysis, malondialdehyde and hydroxynonenal adducts were observed in chondrocyte-matrix extracts, and the amount of adducts increased with calcium ionophore treatment. Furthermore, vitamin E diminished aldehyde-protein adduct formation in activated extracts, which suggests that vitamin E has an antioxidant role in preventing protein oxidation. This study provides in vitro evidence linking chondrocyte lipid peroxidation to cartilage matrix protein (collagen) oxidation and degradation and suggests that vitamin E has a preventive role. These observations indicate that chondrocyte lipid peroxidation may have a role in the pathogenesis of cartilage aging and osteoarthritis.

Topics: Aldehydes; Animals; Ascorbic Acid; Cartilage; Cells, Cultured; Chondrocytes; Collagen; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix Proteins; Glycoproteins; Immunoblotting; Ionophores; Lipid Peroxidation; Lipopolysaccharides; Matrilin Proteins; Metalloendopeptidases; Nitric Oxide; Osteoarthritis; Phagocytosis; Phenanthrolines; Protease Inhibitors; Rabbits; Reactive Oxygen Species; Time Factors; Vitamin E

The application of mechanical loads to bone cells in vitro has been found to generate variable responses, which may in part be due to the source of the cell used and the characteristics of the strain applied. The aim of this study was to establish a system for applying well-defined physiological levels of mechanical strain to a well-defined population of human osteoblast-like cells. Human bone-derived cells obtained from the greater trochanter of the femur during total hip arthroplasty for osteoarthritis were cultured in the presence of 10 nmol/L dexamethasone and 100 mumol/L L-ascorbate-2-phosphate. Replicates of cells from each patient were loaded on separate occasions using controlled cyclical strains of 4000 microstrain (mu epsilon) or less. Strain gauges recorded reliable, reproducible strains between 1000 and 6000 mu epsilon. To establish reproducibility, sequential explant cultures derived from two patients were studied. A consistent increase (p < 0.05) in proliferation between replicates and explants derived from one patient subjected to 1600 mu epsilon on separate occasions was observed. Cells derived from sequential explants of the second patient showed no consistent increase in proliferation between replicates and explants. Three of six patients showed a significant increase (p < 0.05) in PGE2 production after 5 h in response to stretch (4000 mu epsilon) in all replicates on separate occasions, whereas, in the other three populations of cells, no increase in PGE2 was measured in any of the replicates. These results show that the application of highly controlled strains causes a significant effect on human bone cells, but only in a proportion of subjects. The response is consistent between sequential explants derived from the same patient. The implications of this study are that human osteoblast-like cells do respond to physiological strain in vitro, although some cells are more strain sensitive than others.

Topics: Anti-Inflammatory Agents; Arthroplasty, Replacement, Hip; Ascorbic Acid; Cell Division; Cells, Cultured; Dexamethasone; Dinoprostone; Femur; Humans; Osteoarthritis; Osteoblasts; Reproducibility of Results; Stress, Mechanical

The signs and symptoms of osteoarthritis are common complaints seen in patients suffering with chronic temporomandibular disorders (TMD), specifically, internal derangements with a diagnosis of osteoarthritis. With or without the complaints of pain and swelling, joint noises are bothersome and annoying to both the patient and at times, to those seated close to the patient during mealtime. In fact, many patients are driven to seek care by family members because of his or her TMJ noises. For years in veterinarian medicine, glucosamine and chondroitin sulfates have been used to treat symptoms of osteoarthritis. Recently, the use of these two supplements has been recommended for human beings as well. Reports of decreased joint noises, pain and swelling after the administration of therapeutic doses of these supplements have sparked an interest in their possible use in the treatment of osteoarthritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Chondrogenesis; Chondroitin Sulfates; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Temporomandibular Joint Disorders

Topics: Antioxidants; Ascorbic Acid; Diet; Humans; Obesity; Osteoarthritis; Vitamin D; Vitamin E

Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a pathway that leads to many of the degenerative changes associated with aging. We hypothesized that increased intake of antioxidant micronutrients might be associated with decreased rates of osteoarthritis (OA) in the knees, a common age-related disorder.. Participants in the Framingham Osteoarthritis Cohort Study underwent knee evaluations by radiography at examinations 18 (1983-1985) and 22 (1992-1993). Usual dietary intake was assessed using the Food Frequency Questionnaire, administered at examination 20 (1988-1989). Knees without OA at baseline (Kellgren and Lawrence [K&L] grade < or = 1) were classified as having incident OA if they had a K&L grade > or = 2 at followup. Knees with OA at baseline were classified as having progressive OA if their score increased by > or = 1 at followup. Knees were also classified as having cartilage loss or osteophyte growth if their maximal joint space narrowing or osteophyte growth score increased by > or = 1 (range 0-3). The association of vitamin C, beta carotene, and vitamin E intake, ranked in sex-specific tertiles, with incidence and progression of OA was compared with that of a panel of nonantioxidant vitamins, Bl, B6, niacin, and folate, using logistic regression and generalized estimation equations to adjust for correlation between fellow knees. The lowest tertile for each dietary exposure was used as the referent category. Odds ratios (OR) were adjusted for age, sex, body mass index, weight change, knee injury, physical activity, energy intake, and health status.. Six hundred forty participants received complete assessments. Incident and progressive OA occurred in 81 and 68 knees, respectively. We found no significant association of incident OA with any nutrient. A 3-fold reduction in risk of OA progression was found for both the middle tertile (adjusted OR = 0.3, 95% confidence interval [95% CI] 0.1-0.8) and highest tertile (adjusted OR = 0.3, 95% CI 0.1-0.6) of vitamin C intake. This related predominantly to a reduced risk of cartilage loss (adjusted OR = 0.3, 95% CI 0.1-0.8). Those with high vitamin C intake also had a reduced risk of developing knee pain (adjusted OR = 0.3, 95% CI 0.1-0.8). A reduction in risk of OA progression was seen for beta carotene (adjusted OR = 0.4, 95% CI 0.2-0.9) and vitamin E intake (adjusted OR = 0.7, 95% CI 0.3-1.6), but was less consistent. No significant associations were observed for the nonantioxidant nutrients.. High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA. We found no effect of antioxidant nutrients on incident OA. These preliminary findings warrant confirmation.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Disease Progression; Feeding Behavior; Female; Humans; Incidence; Knee Joint; Male; Micronutrients; Osteoarthritis; Retrospective Studies; Vitamin E

Expression of beta 1 integrins was studied in vitro as articular chondrocytes reestablished a matrix in culture and in situ in a nonhuman primate model of osteoarthritis in order to investigate a potential role for integrins in mediating cell-extracellular matrix interactions in cartilage. Chondrocytes were found to express alpha 1 beta 1, alpha 3 beta 1, and alpha 5 beta 1 integrins both in vitro and in situ. Cell surface expression of beta 1 integrins increased as chondrocytes were maintained in cultured from 3 to 7 days. Increased beta 1 integrin expression was also observed in osteoarthritic cartilage compared with normal cartilage. The greatest relative increase in both systems was noted for the alpha 1 beta 1 integrin. The increase in chondrocyte beta 1 integrin expression in vitro was noted in both monolayer and alginate cultures and occurred prior to detectable changes in the differentiated phenotype of the chondrocyte. Disruption of the cytoskeleton with the drug dihydrocytochalasin B inhibited the cell culture induced increase in integrin expression, while treatment of cultured cells with TGF-beta resulted in increased expression of the alpha 5 beta 1 integrin. The modulation of beta 1 integrin expression noted in vitro and in situ indicates that chondrocytes are capable of regulated expression of beta 1 integrins and suggests that beta 1 integrins may play an important role in mediating chondrocyte-extracellular matrix interactions in cartilage.

Topics: Animals; Ascorbic Acid; Base Sequence; Cartilage, Articular; Cattle; Cell Adhesion; Cell Membrane; Cells, Cultured; Cytochalasin B; Cytoskeleton; Disease Models, Animal; DNA Primers; Extracellular Matrix; Humans; Integrin beta1; Integrins; Lymphotoxin-alpha; Macaca fascicularis; Molecular Sequence Data; Osteoarthritis; RNA, Messenger

Cartilage degeneration was induced in the hind knees of guinea-pigs by surgery. Partial medial meniscectomy induced rapidly progressing lesions whereas the lesions induced by section of the lateral collateral ligament with or without section of the medial collateral ligament developed later and progressed more slowly. In all cases the lesions were first seen focally on the medial tibial plateau where they extended both laterally and deeper into the cartilage. Later, lesions appeared on the medial femoral condyle and meniscus, and eventually also on cartilage in the lateral joint compartment. During the later stages, these models had many features of human osteoarthritis. The appearance and progression of spontaneous lesions in the hyaline cartilage of the hind knees of young guinea-pigs first reported by Bendele and Hulman (1988) has been confirmed. Extra ascorbic acid added to the drinking water had a slight chondroprotective effect on the development of spontaneous lesions but gave no significant protection against the development of lesions induced by lateral collateral ligament section.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Drinking; Guinea Pigs; Knee Joint; Ligaments, Articular; Male; Menisci, Tibial; Osteoarthritis

The responsiveness of human synovial cells and chondrocytes to L-ascorbate, CTAP Ib, III, IV and V was assessed by assays which measured DNA and glycosaminoglycan synthesis and plasminogen activator formation. Differences in behavior were noted between synovial and cartilage derived cells and between normal and OA chondrocytes.

Topics: Ascorbic Acid; Cartilage, Articular; Cells, Cultured; DNA; Glycosaminoglycans; Growth Substances; Humans; Osteoarthritis; Peptides; Plasminogen Activators; Synovial Membrane

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Guinea Pigs; Osteoarthritis; Proteoglycans; Vitamin E

The effect of variation in dietary ascorbic acid on surgically induced osteoarthritis was examined in the stifle joints of guniea pigs. Two different surgical procedures were used to induce osteoarthritis in the right stifle joint of these animals. Guinea pigs were maintained either on a high (150 mg/day) or low (2.4 mg/day) dietary intake of vitamin C. Regardless of the surgical procedure used to induce osteoarthritis, the animals maintained on the high level of vitamin C consistently showed severe joint damage than animals on the low level of the vitamin.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Female; Guinea Pigs; Hindlimb; Male; Menisci, Tibial; Methods; Osteoarthritis

Developing osteoarthritis, surgically induced in the right hind knee joint of guinea pigs by different procedures (A or B), was studied in animals maintained on either minimal or supplemented levels of dietary vitamin C. Procedure A, consisting of transecting the anterior cruciate and major portion of the medial collateral ligaments, resulted in a slower developing and less severe form of the disease than procedure B which also included a partial menisectomy. Regardless of the surgical procedure used, animals on minimal levels of ascorbate always exhibited more severe pathology than those on high levels. When compared with controls, a significant enhancement of acid phosphatase characterized arthritic cartilage in both supplemented and minimal diet groups, although the increase was 2-fold greater in the latter. In addition, a significant elevation of arylsulfatase A and B activities was observed only in the minimal diet group. Early stages of pathology in both diet groups were characterized by formation of repair cartilage which stained strongly with Safranin O on histologic sections. As the disease progressed, pitting, ulcerations, and eburnation occurred in the minimal diet group. Cartilage weight in normal joints was greater for guinea pigs kept on high levels of vitamin C. It is likely that this stimulated synthesis of cartilage in the supplemented animals protected against the erosion of the articular cartilage which characterized the more severe disease process in the guinea pigs on minimal levels of ascorbate.

Topics: Animals; Ascorbic Acid; Cartilage, Articular; DNA; Guinea Pigs; Knee Joint; Lysosomes; Osteoarthritis

Sulfated proteoglycan structure and metabolism in osteoarthritic articular cartilage from the hind-limb joints of guinea pigs in which the disease had been surgically induced were evaluated and compared with those from nonoperated or sham-operated controls. In these studies, conducted on animals receiving high and low dietary levels of ascorbic acid, the effect of vitamin C on these variables was also examined. Sulfated proteoglycan biosynthesis per unit of DNA as reflected by in vivo uptake of 35S-sulfate was stimulated both by arthritic development and high dietary vitamin C. Under these conditions, the specific activities, 35S-cpm/micrograms uronic acid, of the proteoglycans were elevated. Neither arthritic development nor variation in dietary levels of vitamin C altered the structure of the proteoglycans. Two species of proteoglycans that exhibited the same electrophoretic mobilities in agarose/acrylamide gels, the same elution profiles on high performance liquid chromatography,, and the same galactosamine/glucosamine ratios were found in all normal and osteoarthritic cartilage specimens tested. The specific activities of these two specimens tested. The specific activities of these two species were dissimilar. In all samples, the larger of the two species had a higher specific activity.

Topics: Animals; Ascorbic Acid; Cartilage, Articular; Chemical Phenomena; Chemistry; Chondroitin Sulfate Proteoglycans; Chromatography, High Pressure Liquid; Electrophoresis; Guinea Pigs; Osteoarthritis; Proteoglycans; Reference Values; Tissue Distribution

A correlation between increased arylsulfatase activities and decreased sulfated proteoglycan content in human osteoarthritic articular cartilage suggested a possible interrelationship between these parameters. Since we had previously shown that ascorbate caused a decrease in levels of arylsulfatase A and B activities in normal chondrocyte cultures, the validity of the above relationship was examined by measuring the effect of vitamin C on the biosynthesis and distribution of 35S-labeled proteoglycans and arylsulfatase A and B activities in cell extracts of chondrocytes derived from normal and osteoarthritic tissue. Arylsulfatase A and B activities were found to be reduced in the presence of ascorbic acid in all normal and osteoarthritic cell lines examined when measured 3, 6, 10, and 13 days after the introduction of the vitamin in the culture medium. Acid phosphatase activity, on the other hand, was found to be elevated in the presence of ascorbate. The inhibitory effect by ascorbic acid on arylsulfatase activities could be reversed by withdrawing the vitamin from the nutrient medium. Addition of EDTA to the cell extracts before assay also reversed the inhibiton. Sulfated proteoglycan biosynthesis as reflected in 35S-sulfate uptake per milligram of DNA was significantly increased in the presence of ascorbic acid. The distribution of the newly synthesized molecules between the cell layer and medium fractions was altered. In the presence of ascorbate, more deposition into the cell layer of newly synthesized macromolecules occurred. These data suggest an inverse relationship between arylsulfatase activities and the stability of the newly synthesized sulfated proteoglycans in the extracellular matrix.

Topics: Acid Phosphatase; Arylsulfatases; Ascorbic Acid; Cartilage, Articular; Cell Line; Cerebroside-Sulfatase; Chondro-4-Sulfatase; Chondroitin Sulfate Proteoglycans; Edetic Acid; Humans; Osteoarthritis; Proteoglycans; Sulfatases

Topics: Adult; Alkaptonuria; Ascorbic Acid; Humans; Male; Methylthiouracil; Middle Aged; Osteoarthritis; Radiography; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Ascorbic Acid; Flavones; Hesperidin; Osteoarthritis; Vitamins

Topics: Ascorbic Acid; Humans; Methylthiouracil; Ochronosis; Osteoarthritis; Thiouracil; Vitamins

Topics: Arthritis, Rheumatoid; Ascorbic Acid; Desoxycorticosterone; Desoxycorticosterone Acetate; Disease; Humans; Osteoarthritis; Sciatic Nerve; Sciatica; Spondylitis

Topics: Adrenal Cortex Hormones; Ascorbic Acid; Desoxycorticosterone Acetate; Osteoarthritis; Vitamins