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1.
J Fish Biol ; 104(1): 310-314, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37721715

ABSTRACT

Identifying the factors that influence the citation of articles helps authors improve the impact and reach of their research. Analysis of publications in the Journal of Fish Biology between 2008 and 2021 revealed that variables such as the number of keywords, abstract length, number of authors, and page length were associated with higher impact papers. These trends applied to both review and regular papers. These findings suggest that papers that are more informative, have higher numbers of authors, and have more keywords are more likely to be cited. Adoption of some simple "best-practice" behaviors can improve the likelihood that a paper is cited.


Subject(s)
Fishes , Journal Impact Factor , Animals , Biology
2.
Rev Med Liege ; 75(5-6): 369-375, 2020 May.
Article in French | MEDLINE | ID: mdl-32496682

ABSTRACT

The development of new drugs is a significant activity in a university hospital that favors access to therapeutic novelties to patients. Rheumatology, whose drug armamentarium was poor in the 1980s, has benefited from the huge progresses of immunology in the 1980-1990s, allowing a therapeutic revolution in whom the academic hospital of Liège (CHU Liège) has been strongly implicated. First protocols with anti-TNF-? monoclonal antibodies have been applied in 1997. Sixty-one protocols have been initiated in rheumatoid arthritis, 12 in ankylosing spondylitis, 10 in psoriatic arthritis, 9 in systemic erythematosus lupus, 3 in giant cell arteritis, 1 in polymyalgia rheumatica, 5 in osteoarthritis and 4 in osteoporosis. Potential and pitfalls will be discussed disease by disease and also by drug categories. The balance remains globally positive, but remission is far from be reached.


La recherche clinique médicamenteuse est une activité importante dans un hôpital universitaire. Elle valide des nouveautés thérapeutiques et fait bénéficier les patients de traitements novateurs bien avant leur mise sur le marché. La rhumatologie est une discipline dont l'arsenal thérapeutique était pauvre dans les années 1980, et les immenses progrès de l'immunologie, réalisés entre 1980 et 1995, lui ont permis de vivre une véritable révolution thérapeutique à laquelle notre service a amplement participé. C'est en 1997 que les premiers traitements par anticorps monoclonaux anti-TNF-? (les traitements dits biologiques) ont été utilisés au CHU de Liège. Soixante et une études seront initiées dans la polyarthrite rhumatoïde, 12 dans la spondylarthrite ankylosante, 10 dans la polyarthrite psoriasique, 9 dans le lupus érythémateux disséminé, 3 dans l'artérite temporale de Horton, une dans la pseudopolyarthrite rhizomélique, une dans la sclérodermie, 5 dans l'arthrose, 4 dans l'ostéoporose. Les espoirs et les déceptions observées dans les différentes indications, et avec les différentes molécules, sont analysées. Le bilan est globalement positif, mais les résultats encore insuffisants que pour arriver au concept de rémission.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Polymyalgia Rheumatica , Rheumatology , Humans , Rheumatology/trends , Tumor Necrosis Factor-alpha
3.
Sci Rep ; 7(1): 5440, 2017 07 14.
Article in English | MEDLINE | ID: mdl-28710357

ABSTRACT

While the direct physical impact on seabed biota is well understood, no studies have defined thresholds to inform an ecosystem-based approach to managing fishing impacts. We addressed this knowledge gap using a large-scale experiment that created a controlled gradient of fishing intensity and assessed the immediate impacts and short-term recovery. We observed a mosaic of taxon-specific responses at various thresholds. The lowest threshold of significant lasting impact occurred between 1 and 3 times fished and elicited a decrease in abundance of 39 to 70% for some sessile epifaunal organisms (cnidarians, bryozoans). This contrasted with significant increases in abundance and/or biomass of scavenging species (epifaunal echinoderms, infaunal crustaceans) by two to four-fold in areas fished twice and more. In spite of these significant specific responses, the benthic community structure, biomass and abundance at the population level appeared resilient to fishing. Overall, natural temporal variation in community metrics exceeded the effects of fishing in this highly dynamic study site, suggesting that an acute level of disturbance (fished over six times) would match the level of natural variation. We discuss the implications of our findings for natural resources management with respect to context-specific human disturbance and provide guidance for best fishing practices.


Subject(s)
Biota/physiology , Conservation of Natural Resources/methods , Fisheries/statistics & numerical data , Fishes/physiology , Food Chain , Animals , Biomass , Bryozoa/physiology , Cnidaria/physiology , Crustacea/physiology , Echinodermata/physiology , Ecosystem , Humans , Population Density
4.
Rev Med Liege ; 71(3): 124-8, 2016 Mar.
Article in French | MEDLINE | ID: mdl-27311243

ABSTRACT

Over recent years, anti-TNFα have been used to treat rheumatoid arthritis. The principal secondary effect of anti-TNFα is tuberculosis infections. Another paradoxical effect, previously less well understood, is the development of sarcoid-like granulomatous reactions. We report the case of a 36 year old woman who had been treated for 9 years with anti-TNF alpha. She developed a pulmonary sarcoid-like gra-nulomatosis, complication that is rare but not exceptional in patients treated with TNF-blockers. Discontinuation of anti TNF usually led to recovery. It has been suggested that these reactions mainly occur with etanercept, but this requires further confirmation.


Subject(s)
Etanercept/adverse effects , Granuloma/chemically induced , Sarcoidosis, Pulmonary/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Etanercept/therapeutic use , Female , Granuloma/pathology , Humans , Sarcoidosis, Pulmonary/pathology
5.
J Nutr Health Aging ; 17(4): 326-31, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23538654

ABSTRACT

BACKGROUND: The European Society for Clinical Nutrition and Metabolism (ESPEN) has recommended the Mini Nutritional Assessment (MNA®), the Nutritional Risk Screening 2002 (NRS), and the Malnutrition Universal Screening Tool (MUST) for nutritional screening in various settings and age groups. While in recent years all three tools have been applied to nursing home residents, there is still no consensus on the most appropriate screening tool in this specific setting. AIM: The present study aims at comparing the MNA, the NRS, and the MUST with regard to applicability, categorization of nutritional status, and predictive value in the nursing home setting. METHOD: MNA, NRS, and MUST were performed on 200 residents from two municipal nursing homes in Nuremberg, Germany. Follow-up data on infection, hospitalization, and mortality were collected after six and again after twelve months. RESULTS: Among 200 residents (mean age 85.5 ± 7.8 years) the MNA could be completed in 188 (94.0%) and the NRS and MUST in 198 (99.0%) residents. The prevalence of 'malnutrition' according to the MNA was 15.4%. The prevalence of 'risk of malnutrition' (NRS) and 'high risk of malnutrition' (MUST), respectively, was 8.6% for both tools. The individual categorization of nutritional status showed poor agreement between NRS and MUST on the one hand and MNA on the other. For all tools a significant association between nutritional status and mortality was demonstrated during follow-up as classification in 'malnourished', respectively 'high risk of malnutrition' or 'nutritional risk', was significantly associated with increased hazard ratios. However, the MNA showed the best predictive value for survival among well-nourished residents. CONCLUSION: The evaluation of nutritional status in nursing home residents by MNA, NRS, and MUST shows significant differences. This observation may be of clinical relevance as nutritional intervention is usually based on screening results. As the items of the MNA reflect particularities of the nursing home population, this tool currently appears to be the most suitable one in this setting.


Subject(s)
Homes for the Aged , Malnutrition/diagnosis , Nursing Homes , Nutrition Assessment , Nutritional Status , Aged , Aged, 80 and over , Female , Follow-Up Studies , Geriatric Assessment , Germany , Hospitalization , Humans , Male , Malnutrition/prevention & control , Proportional Hazards Models , Risk Assessment , Risk Factors , Surveys and Questionnaires
6.
J Nutr Health Aging ; 17(4): 351-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23538658

ABSTRACT

OBJECTIVE: This study investigates the association between MNA results and frailty status in community-dwelling older adults. In addition the relevance of singular MNA items and subscores in this regard was tested. DESIGN: Cross-sectional study. SETTING: Community-dwelling older adults were recruited in the region of Nürnberg, Germany. PARTICIPANTS: 206 volunteers aged 75 years or older without cognitive impairment (Mini Mental State Examination >24 points), 66.0% female. MEASUREMENTS: Frailty was defined according to Fried et al. as presence of three, pre-frailty as presence of one or two of the following criteria: weight loss, exhaustion, low physical activity, low handgrip strength and slow walking speed. Malnutrition (<17 points) and the risk of malnutrition (17-23.5 points) were determined by MNA®. RESULTS: 15.1% of the participants were at risk of malnutrition, no participant was malnourished. 15.5 % were frail, 39.8% pre-frail and 44.7% non-frail. 46.9% of the frail, 12.2% of the pre-frail and 2.2% of the non-frail participants were at risk of malnutrition (p<0.001). Hence, 90% of those at risk of malnutrition were either pre-frail or frail. For the anthropometric, dietary, subjective and functional, but not for the general MNA subscore, frail participants scored significantly lower than pre-frail (p<0.01), and non-frail participants (p<0.01). Twelve of the 18 MNA items were also significantly associated with frailty (p<0.05). CONCLUSIONS: These results underline the close association between frailty syndrome and nutritional status in older persons. A profound understanding of the interdependency of these two geriatric concepts will represent the basis for successful treatment strategies.


Subject(s)
Frail Elderly , Malnutrition/diagnosis , Malnutrition/epidemiology , Nutrition Assessment , Nutritional Status , Aged , Aged, 80 and over , Cross-Sectional Studies , Diet , Fatigue , Female , Geriatric Assessment/methods , Germany , Hand Strength , Humans , Male , Prevalence , Surveys and Questionnaires , Weight Loss
7.
Dtsch Med Wochenschr ; 136(5): 176-8, 2011 Feb.
Article in German | MEDLINE | ID: mdl-21271475

ABSTRACT

Malnutrition, which occurs in 27.4% of all elderly persons, is a great burden to those affected and for the health services. There are multiple causes for malnutrition, such as loss of appetite, poorly balanced diet, dementia, dysphagia chewing problems, as well as gastrointestinal disorders. Presence of weight loss and/or anorexia point towards malnutrition. A prerequisite for properly targeted nutritional intervention is to distinguish between sarcopenia and kachexia. In addition the "Mini Nutritional Assessment" (MNA (®)) questionnaire can be used quickly and reliably for diagnose malnutrition as recommended by the European Society for Clinical Nutrition and Metabolism. Treatment should be based on an individually designed nutritional regime, which incorporates eating habits and functional impairment of the patient.


Subject(s)
Protein-Energy Malnutrition/diagnosis , Aged , Aged, 80 and over , Cachexia/diagnosis , Cachexia/epidemiology , Cachexia/etiology , Cachexia/therapy , Causality , Cross-Sectional Studies , Geriatric Assessment , Germany , Humans , Nutrition Assessment , Nutrition Therapy/methods , Protein-Energy Malnutrition/epidemiology , Protein-Energy Malnutrition/etiology , Protein-Energy Malnutrition/therapy , Risk Factors , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Sarcopenia/etiology , Sarcopenia/therapy
8.
J Fish Biol ; 76(9): 2261-86, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20557662

ABSTRACT

Recent global and regional exercises have been undertaken to identify 100 questions of relevance to policy makers that, if answered, would improve decision making and conservation actions. These were intentionally broad, but all included themes and questions of relevance to aquatic and fisheries professionals (e.g. exploitation, habitat alteration, effectiveness of protected areas, migratory connectivity and environmental effects of aquaculture). Here, the content of the global 100 question exercise relevant to aquatic and fisheries issues is summarized and a critical analysis is provided. Many of the questions addressed in apparently unrelated themes and topics (e.g. terrestrial, agriculture and energy policy) have potential relevance to fisheries and aquatic habitats, which underlines the connectivity between terrestrial and aquatic realms. Given the intimate link between aquatic environmental problems and human activities (including culture and economics), greater understanding of the human dimension is required to inform decision making. Stakeholder perspectives need to be included as a core component of the fisheries management triangle (i.e. managing fish, habitat and people). The benefits and risks of conducting a global 100 questions exercise with an exclusive focus on questions of relevance to fisheries and aquatic practitioners are also considered. There is no question that evidence-based approaches to conservation are essential for addressing the many threats that face aquatic ecosystems and reverse the imperilment trends among ichthyofauna. It is still unclear, however, as to the extent to which 100 questions exercises will help to achieve conservation and management targets for aquatic resources. A global 100 questions exercise that focused on fisheries and aquatic issues would certainly help to generate interest and awareness sufficient to justify such an exercise.


Subject(s)
Biodiversity , Conservation of Natural Resources/methods , Fisheries , Public Policy , Decision Making , Surveys and Questionnaires
9.
Aging Male ; 12(4): 87-94, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19909201

ABSTRACT

Frailty has become one of the 'hot spots' in geriatric research. Frailty has multifactorial origin, and is regarded as a fundamental risk factor for deteriorating health status and disability in elderly people and is highly prevalent in the population above the age 65. It is estimates that prevalence rates up to 27% and pre-frailty rates up to 50% qualify for the term "epidemic". Although the role of nutritional deficiency in the development of age-related frailty was suggested long ago, research conducted in this area is relatively recent. The critical role of micronutrients in this context suggests the need to improve the quality of food eaten by elderly people whereas quantity of food appears to be less relevant. This review summarizes the recent literature on the nutritional pathways to frailty with particular focus on the effect of energy, protein and micronutrients.


Subject(s)
Geriatric Assessment , Malnutrition/prevention & control , Aged , Aging/physiology , Antioxidants/metabolism , Congresses as Topic , Female , Frail Elderly , Humans , Italy , Male , Micronutrients/metabolism
10.
J Nutr Health Aging ; 13(9): 782-8, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19812868

ABSTRACT

OBJECTIVE: To validate a revision of the Mini Nutritional Assessment short-form (MNA(R)-SF) against the full MNA, a standard tool for nutritional evaluation. METHODS: A literature search identified studies that used the MNA for nutritional screening in geriatric patients. The contacted authors submitted original datasets that were merged into a single database. Various combinations of the questions on the current MNA-SF were tested using this database through combination analysis and ROC based derivation of classification thresholds. RESULTS: Twenty-seven datasets (n=6257 participants) were initially processed from which twelve were used in the current analysis on a sample of 2032 study participants (mean age 82.3y) with complete information on all MNA items. The original MNA-SF was a combination of six questions from the full MNA. A revised MNA-SF included calf circumference (CC) substituted for BMI performed equally well. A revised three-category scoring classification for this revised MNA-SF, using BMI and/or CC, had good sensitivity compared to the full MNA. CONCLUSION: The newly revised MNA-SF is a valid nutritional screening tool applicable to geriatric health care professionals with the option of using CC when BMI cannot be calculated. This revised MNA-SF increases the applicability of this rapid screening tool in clinical practice through the inclusion of a "malnourished" category.


Subject(s)
Geriatric Assessment , Malnutrition/diagnosis , Nutrition Assessment , Surveys and Questionnaires/standards , Aged , Aged, 80 and over , Anthropometry , Body Mass Index , Female , Health Status Indicators , Humans , Male , Malnutrition/epidemiology , Mass Screening/methods , Mass Screening/standards , Nutritional Status , ROC Curve , Sensitivity and Specificity
12.
J Am Med Dir Assoc ; 9(8): 545-51, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19083287

ABSTRACT

The age-associated loss of muscle mass and muscle strength described by the term sarcopenia is highly relevant for functionality among nursing home residents. Nevertheless, the scientific literature concentrating on sarcopenia in this population is scarce. For practical reasons, common definitions of this entity, which rely on dual energy x-ray absorptiometry (DEXA) and bioimpedance analysis (BIA), cannot be applied in this setting. Anthropometric measurements like arm muscle circumference and calf circumference seem to be most suitable. Handgrip may be used as an alternative. Prevalence data show a wide range but are mostly high. There is a close association of the degree of sarcopenia with dependence among residents. The pathophysiology of sarcopenia in this population is strongly influenced by comorbidity and often there is significant overlap with the cachexia syndrome. At present, physical exercise is regarded to be the most promising therapeutic option, with resistance training being superior to endurance programs. Physical exercise has been successful even among Alzheimer patients and physically restrained residents. It has to be accompanied by the provision of adequate and diverse meals based on individual energy and nutrient requirements. Special attention should be paid to the treatment of vitamin D deficiency if present. New therapeutic options include Whole Body Vibration, oral supplements with essential amino acids and leucine, ACE-inhibitors, and cytokine-modifying drugs.


Subject(s)
Muscular Atrophy , Nursing Homes , Humans , Muscular Atrophy/diagnosis , Muscular Atrophy/epidemiology , Muscular Atrophy/physiopathology , Muscular Atrophy/therapy , United States/epidemiology
13.
Ann Rheum Dis ; 64(11): 1647-9, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16227416

ABSTRACT

OBJECTIVES: To assess the incidence of infusion reactions in patients with rheumatoid arthritis (RA) receiving infliximab treatment with and without betamethasone premedication. To determine whether patients with an atopic diathesis had a better response to corticosteroid pretreatment than those without, and the course of patients' functional capacity and quality of life. PATIENTS AND METHODS: A prospective, multicentre, randomised, double blind phase 4 study of 355 patients with RA in two groups: group A received betamethasone and group B placebo, before a 36 week infusion treatment with infliximab. Incidence and severity of infusion reactions from infliximab treatment were assessed. RESULTS: The incidence of reactions to infliximab infusion was <5%. More infusion reactions occurred with betamethasone pretreatment than with placebo. Response to infliximab of patients with atopic backgrounds did not differ in the presence or absence of betamethasone from that of non-atopic patients. Mean Health Assessment Questionnaire score improved by 47% at week 24, quality of life assessed by Short Form-36 improved in mental and physical component subscales. CONCLUSIONS: Incidence of infusion reactions with infliximab was low and their severity generally mild, but betamethasone pretreatment did not decrease the incidence and severity of infusion reactions. Betamethasone, therefore, is not recommended as a systematic prophylactic measure, even in atopic patients.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Betamethasone/therapeutic use , Adult , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/pathology , Double-Blind Method , Drug Therapy, Combination , Female , Health Status Indicators , Humans , Infliximab , Infusions, Intravenous , Male , Middle Aged , Prospective Studies , Quality of Life , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors
15.
Rev Med Liege ; 57(8): 486-92, 2002 Aug.
Article in French | MEDLINE | ID: mdl-12405019

ABSTRACT

Rheumatoïd arthritis (RA) is the most frequent autoimmune inflammatory arthropathy. Chronic synovial inflammation usually results in cartilage destruction, bone erosion and subsequent joint deformities with impaired physical function. These consequences are more or less delayed by standard disease-modifying antirheumatic drugs (DMARDs). A better knowledge of the basic mechanisms of the disease and new biomolecular tools led to the development of novel biological agents including TNF alpha blockers. TNF alpha is a key inflammatory cytokine that plays a critically important role in the pathogenesis of RA. TNF alpha blockers brought dramatic improvements in efficacy of RA treatment. Here we will review the pathophysiological elements of RA wich explain the therapeutic efficacy of these TNF alpha blockers and we will describe in details the molecules, Remicade (Infliximab) and Enbrel (Etanercept), wich will be very soon used in daily practice in Belgium.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Immunoglobulin G/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Antirheumatic Agents/immunology , Antirheumatic Agents/pharmacology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/physiopathology , Belgium , Drug Utilization/statistics & numerical data , Etanercept , Humans , Immunoglobulin G/immunology , Immunoglobulin G/pharmacology , Infliximab , Patient Selection , Practice Patterns, Physicians'/statistics & numerical data , Receptors, Tumor Necrosis Factor/immunology , Tumor Necrosis Factor-alpha/immunology
16.
Rev Med Liege ; 57(5): 274-9, 2002 May.
Article in French | MEDLINE | ID: mdl-12143168

ABSTRACT

Osteoporosis is the most frequent demineralizing disease. However, when a demineralized vertebra is identified, other diseases must be ruled out in the course of diagnosis. Through three clinical cases, we analyze pitfalls that have delayed the diagnosis of one rare, but unfortunately lethal, aetiology: multiple myeloma.


Subject(s)
Bone Demineralization, Pathologic/etiology , Diagnostic Errors , Multiple Myeloma/diagnosis , Osteoporosis/diagnosis , Aged , Diagnosis, Differential , Female , Humans , Hyperthyroidism/diagnosis , Male , Middle Aged , Osteoporosis/complications , Spine/pathology
18.
Ann Rheum Dis ; 61(2): 161-6, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11796404

ABSTRACT

OBJECTIVE: To determine matrix metalloproteinase-3 (MMP-3) serum levels in patients with rheumatic diseases and to study the relation between MMP-3 and C reactive protein (CRP) levels. METHODS: MMP-3 serum levels were determined by enzyme linked immunosorbent assay (ELISA) in (a) patients with active inflammatory rheumatic diseases: rheumatoid arthritis (RA), psoriatic arthritis, polymyalgia rheumatica, acute crystal arthritis, and ankylosing spondylitis; (b) patients with active inflammatory systemic diseases: cutaneo-articular or renal systemic lupus erythematosus (SLE), systemic sclerosis, and vasculitides; (c) patients with non-inflammatory rheumatic diseases: osteoarthritis and fibromyalgia; (d) critically ill patients without rheumatic diseases, representing an acute inflammatory control group; (e) healthy controls. RESULTS: MMP-3 serum levels were significantly increased in patients with active RA, psoriatic arthritis, and polymyalgia rheumatica, whether treated or not by corticosteroids, and in female patients with acute crystal arthritis. MMP-3 serum levels were normal in steroid-free patients with active cutaneo-articular or renal SLE, systemic sclerosis, and vasculitides but were significantly increased in steroid treated patients. MMP-3 levels were normal in fibromyalgia, osteoarthritis, ankylosing spondylitis, and acute inflammatory controls. MMP-3 was significantly correlated with CRP in RA (r=0.5, p=0.0004) but not in any of the other disease groups. CONCLUSIONS: MMP-3 serum levels are increased in inflammatory rheumatic diseases characterised by joint synovitis, such as RA, polymyalgia rheumatica, psoriatic arthritis, and acute crystal arthritis-that is, whether the diseases are acute or chronic, erosive or not. They are normal in SLE, systemic sclerosis, and vasculitides as well as in non-rheumatic inflammatory controls, but are significantly increased by steroids. These data strongly suggest that serum MMP-3 reflects synovial inflammation.


Subject(s)
Arthritis, Rheumatoid/blood , Matrix Metalloproteinase 3/blood , Adult , Aged , Aged, 80 and over , Arthritis, Psoriatic/blood , Arthritis, Rheumatoid/drug therapy , Biomarkers/blood , C-Reactive Protein/analysis , Case-Control Studies , Female , Fibromyalgia/blood , Glucocorticoids/therapeutic use , Humans , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Osteoarthritis/blood , Polymyalgia Rheumatica/blood , Prednisolone/therapeutic use , Scleroderma, Systemic/blood , Spondylitis, Ankylosing/blood , Statistics, Nonparametric , Vasculitis/blood
19.
Arthritis Rheum ; 44(6): 1444-54, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11407707

ABSTRACT

OBJECTIVE: The imbalance between matrix metalloproteinases (MMPs) 1, 3, and 9 and their specific inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1), is a critical step in cartilage injury and angiogenesis in arthritis. To explore the therapeutic potential of TIMP-1 gene transfer in erosive arthritis, the effects of an adenoviral vector (Ad-TIMP-1) were assessed in DBA/1 mice with collagen-induced arthritis (CIA). METHODS: DBA/1 mice with CIA received an intravenous injection of replication-deficient adenovirus containing the human TIMP-1 gene or a control LacZ gene on day 28 postimmunization. The efficiency of gene transfer was determined by serum TIMP-1 detection, measurements of paw swelling, as well as radiologic and histologic examination of the paws. RESULTS: A single administration of Ad-TIMP-1 resulted in detectable serum levels of the exogenous protein for at least 13 days. The incidence and onset of arthritis were not statistically modified after human TIMP-1 gene transfer in DBA/1 mice compared with control mice. However, the severity of inflammation was statistically significantly increased in Ad-TIMP-1-treated mice and a similar trend was observed in the histologic and radiologic scores. With regard to the mechanisms of the worsened effect in the Ad-TIMP-1-treated mice, we observed 1) higher serum levels of anti-type II collagen IgG2a, 2) a significant increase in endogenous soluble tumor necrosis factor receptor I (TNFRI) in sera, and 3) increased labeling of mouse tumor necrosis factor alpha and TNFRI within arthritic joints. CONCLUSION: These findings show that overexpression of TIMP-1 does not prevent osteochondral injury in a mouse model of arthritis. Since MMPs have overlapping properties in terms of their roles in extracellular matrix degradation, angiogenesis, and shedding of cell surface adhesion molecules, cytokines, and cytokine receptors, the paradoxical results obtained suggest that TIMP-1 is probably not the main inhibitor to target.


Subject(s)
Arthritis, Experimental/therapy , Gene Transfer Techniques , Genetic Therapy , Tissue Inhibitor of Metalloproteinase-1/genetics , Adenoviridae , Animals , Arthritis, Experimental/blood , Arthritis, Experimental/chemically induced , Arthritis, Experimental/pathology , Cells, Cultured , Collagen/immunology , Collagen/pharmacology , Edema/chemically induced , Edema/pathology , Flow Cytometry , Foot/pathology , Genetic Vectors , Hindlimb/drug effects , Hindlimb/pathology , Humans , Male , Mice , Mice, Inbred DBA , Receptors, Tumor Necrosis Factor/blood , Synovial Membrane/cytology , Synovial Membrane/immunology , Tissue Inhibitor of Metalloproteinase-1/biosynthesis , Tissue Inhibitor of Metalloproteinase-1/immunology
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