IL-10 and ET-1 as biomarkers of rheumatic valve disease

Objective

To evaluate the immunological profile and gene expression of endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated from a reference service in cardiovascular surgery.

Methods

This was a quantitative, observational and cross-sectional study. Thirty-five subjects (divided into four groups) participated in the study, 25 patients with chronic rheumatic heart disease and ten control subjects. The mean age of the sample studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were female. Inflammatory cytokines (TNF-α, IL-4 and IL-10) were measured and ten mitral valves of patients who underwent first valve replacement were collected for determination of gene expression of endothelin-1 by real time PCR.

Results

Among the groups studied (patients vs. controls), there was a statistically significant difference in IL-10 levels (P=0.002), and no differences in other cytokines. Expression of endothelin-1 was observed in 70% of samples. Quantitatively, average of ET-1 expression was 62.85±25.63%.

Conclusion

Inflammatory cytokine IL-10 participates in the maintenance of chronicity of rheumatic fever in patients who underwent valve replacement and those who are undergoing medical treatment. The expression of endothelin-1 in heart valve lesions in patients undergoing mitral valve replacement confirms its association with inflammatory activity in rheumatic fever.     

Mitral annulus morphologic and functional analysis using real time tridimensional echocardiography in patients submitted to unsupported mitral valve repair

Introduction

Mitral valve repair is the treatment of choice to correct mitral insufficiency, although the literature related to mitral valve annulus behavior after mitral repair without use of prosthetic rings is scarce.

Objective

To analyze mitral annulus morphology and function using real time tridimensional echocardiography in individuals submitted to mitral valve repair with Double Teflon technique.

Methods

Fourteen patients with mitral valve insufficiency secondary to mixomatous degeneration that were submitted to mitral valve repair with the Double Teflon technique were included. Thirteen patients were in FC III/IV. Patients were evaluated in preoperative period, immediate postoperative period, 6 months and 1 year after mitral repair. Statistical analysis was made by repeated measures ANOVA test and was considered statistically significant P<0.05.

Results

There were no deaths, reoperation due to valve dysfunction, thromboembolism or endocarditis during the study. Posterior mitral annulus demonstrated a significant reduction in immediate postoperative period (P<0.001), remaining stable during the study, and presents a mean of reduction of 25.8% comparing with preoperative period. There was a significant reduction in anteroposterior and mediolateral diameters in the immediate postoperative period (P<0.001), although there was a significant increase in mediolateral diameter between immediate postoperative period and 1 year. There was no difference in mitral internal area variation over the cardiac cycle during the study.

Conclusion

Segmentar annuloplasty reduced the posterior component of mitral annulus, which remained stable in a 1-year-period. The variation in mitral annulus area during cardiac cycle remained stable during the study.     

Effect of N-acetylcysteine in hearts of rats submitted to controlled hemorrhagic shock

Introduction

Pharmacological therapy is a strategy for the prevention of complications associated with ischemia and reperfusion injury that occurs after volume replacement in the treatment of hemorrhagic shock.

Objective

The aim of this study was to evaluate the effect of N-acetylcysteine associated with fluid resuscitation in cardiac injury in a rat hemorrhagic shock model.

Methods

Mice Wister male rats were randomly and subjected to controlled hemorrhagic shock for 60 min. and then, subjected to resuscitation with Ringer lactate. In a group of six animals, 150mg/kg of N-acetylcysteine were added to fluid volume replacement. The animals were observed for 120 min and after this period, were euthanized and cardiac tissue was collected for histopathological analysis and measurement of thiobarbituric acid reactive substances and pro-and anti-inflammatory interleukin.

Results

Cardiac tissue of the group treated with N-acetylcysteine showed lower concentrations of thiobarbituric acid reactive substances (0.20±0.05 vs. 0.27±0.05, P=0.014) and reduced histopathological damage and edema when compared to the group whose volume replacement occurred only with Ringer lactate. There was no difference in the expression of cytokines interleukin 6 (2,138.29±316.89 vs. 1,870.16±303.68, P=0.091) and interleukin 10 (1.019,83±262,50 vs. 848.60±106.5, P=0.169) between the treated groups.

Conclusion

The association of N-acetylcysteine on volume replacement attenuates oxidative stress in the heart, as well myocardial damage and edema, but does not modify the expression of inflammatory cytokines.     

Muscle spasticity associated with reduced whole-leg perfusion in persons with spinal cord injury

Objective

To determine the association between peripheral blood flow and spasticity in individuals with spinal cord injury (SCI).

Design

A cross-sectional study with measurements of muscle spasticity and whole-limb blood flow in individuals with SCI.

Setting

University of Texas at Austin and Brain & Spine Recovery Center, Austin, TX, USA.

Participants

Eighteen individuals (14 males and 4 females) with SCI were classified into high (N = 7), low (N = 6), and no (N = 5) spasticity groups according to the spasticity levels determined by the modified Ashworth scale scores.

Interventions

Whole-limb blood flow was measured in the femoral and brachial arteries using Doppler ultrasound and was normalized to lean limb mass obtained with dual-energy X-ray absorptiometry.

Outcome measures

Limb blood flow and muscle spasticity.

Results

Age, time post-SCI, and the American Spinal Injury Association impairment scale motor and sensory scores were not different among groups with different muscle spasticity. Femoral artery blood flow normalized to lean leg mass was different (P = 0.001) across the three spasticity groups (high 78.9 ± 16.7, low 98.3 ± 39.8, no 142.5 ± 24.3 ml/minute/kg). Total leg muscle spasticity scores were significantly and negatively correlated with femoral artery blood flow (r = −0.59, P < 0.01). There was no significant difference in brachial artery blood flow among the groups.

Conclusions

Whole-leg blood flow was lower in individuals with greater spasticity scores. These results suggest that a reduction in lower-limb perfusion may play a role, at least in part, in the pathogenesis leading to muscle spasticity after SCI.     

Randomized controlled trial of pharmacological replacement of melatonin for sleep disruption in individuals with tetraplegia

Objective

To determine the effectiveness of a melatonin agonist for treating sleep disturbances in individuals with tetraplegia.

Design

Placebo-controlled, double-blind, crossover, randomized control trial.

Setting

At home.

Participants

Eight individuals with tetraplegia, having an absence of endogenous melatonin production and the presence of a sleep disorder.

Interventions

Three weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover, randomized order) with 2 weeks of baseline prior to and 2 weeks of washout between active conditions.

Outcome

Change in objective and subjective sleep.

Measures

Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale, SF-36.

Results

We observed no consistent changes in either subjective or objective measures of sleep, including subjective sleep latency (P = 0.55, Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35, Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or objective sleep efficiency (P = 0.78, Friedman test). There were significant increases in both objective total sleep time (P < 0.05, Friedman test), subjective time in bed (P < 0.05, Friedman test), and subjective sleep quality (P < 0.05, Friedman test), although these occurred in both arms. There were no significant changes in any of the nine SF-36 subscale scores (Friedman test, Ps >Bonferroni adjusted α of 0.005).

Conclusion

In this pilot study, we were unable to show effectiveness of pharmacological replacement of melatonin for the treatment of self-reported sleep problems in individuals with tetraplegia.

Trial Registration

ClinicalTrials.gov # {"type":"clinical-trial","attrs":{"text":"NCT00507546","term_id":"NCT00507546"}}NCT00507546.     

Assessment of passive knee stiffness and viscosity in individuals with spinal cord injury using pendulum test

Objective

Stiffness and viscosity represent passive resistances to joint motion related with the structural properties of the joint tissue and of the musculotendinous complex. Both parameters can be affected in patients with spinal cord injury (SCI). The purpose of this study was to measure passive knee stiffness and viscosity in patients with SCI with paraplegia and healthy subjects using Wartenberg pendulum test.

Design

Non-experimental, cross-sectional, case–control design.

Setting

An outpatient physical therapy clinic, University of social welfare and Rehabilitation Science, Iran.

Patients

A sample of convenience sample of 30 subjects participated in the study. Subjects were categorized into two groups: individuals with paraplegic SCI (n = 15, age: 34.60 ± 9.18 years) and 15 able-bodied individuals as control group (n = 15, age: 30.66 ± 11.13 years).

Interventions

Not applicable.

Main measures

Passive pendulum test of Wartenberg was used to measure passive viscous-elastic parameters of the knee (stiffness, viscosity) in all subjects.

Results

Statistical analysis (independent t-test) revealed significant difference in the joint stiffness between healthy subjects and those with paraplegic SCI (P = 0.01). However, no significant difference was found in the viscosity between two groups (P = 0.17). Except for first peak flexion angle, all other displacement kinematic parameters exhibited no statistically significant difference between normal subjects and subjects with SCI.

Conclusions

Patients with SCI have significantly greater joint stiffness compared to able-bodied subjects.     

Elevated leptin expression in rat model of traumatic spinal cord injury and femoral fracture

Background

Few studies have reported a relationship between leptin induced by spinal cord injury (SCI) and healing bone tissue.

Objective

To observe serum and callus leptin expression within the setting of fracture and traumatic SCI.

Methods

Seventy-two male Sprague Dawley rats were randomized equally into four groups: control, SCI group, fracture group, and fracture/SCI group. Rats were sacrificed at 7, 14, 21, and 28 days post-fracture/SCI. Serum leptin was detected using radioimmunoassay at 1, 7, 14, 21, and 28 days, and callus formation was measured radiologically at 14, 21, and 28 days. Callus leptin was analyzed by means of immunohistochemistry.

Results

Serum leptin in the fracture group, SCI group, and combined fracture/SCI group were all significantly increased compared to control group at the 1, 7, 14, and 2-day time points (P < 0.05). Serum leptin in the combined fracture/SCI group was significantly higher than in the fracture group at 7, 14, and 21 days (P < 0.05), and higher than in SCI groups at 14 and 21days after operation (P < 0.05). The percentage of leptin-positive cells in the fracture/SCI callus, and callus volume was significantly higher than in the fracture-only group (P < 0.001).

Conclusions

Overall, elevated leptin expression was demonstrated within healing bone especially in the 21 days of a rat model combining fracture and SCI. A close association exists between leptin levels and the degree of callus formation in fractures.     

Examining implicit bias of physicians who care for individuals with spinal cord injury: A pilot study and future directions

Context

Despite evidence that healthcare providers have implicit biases that can impact clinical interactions and decisions, implicit bias among physicians caring for individuals with spinal cord injury (SCI) has not been examined.

Objective

Conduct a pilot study to examine implicit racial bias of SCI physicians and its association with functioning and wellbeing for individuals with SCI.

Design

Combined data from cross-sectional surveys of individuals with SCI and their SCI physicians.

Setting

Four national SCI Model Systems sites.

Participants

Individuals with SCI (N = 162) and their SCI physicians (N = 14).

Outcome measures

SCI physicians completed online surveys measuring implicit racial (pro-white/anti-black) bias. Individuals with SCI completed questionnaires assessing mobility, physical independence, occupational functioning, social integration, self-reported health, depression, and life satisfaction. We used multilevel regression analyses to examine the associations of physician bias and outcomes of individuals with SCI.

Results

Physicians had a mean bias score of 0.62 (SD = 0.35), indicating a strong pro-white/anti-black bias. Greater physician bias was associated with disability among individuals with SCI in the domain of social integration (odds ratio = 4.80, 95% confidence interval (CI) = 1.44, 16.04), as well as higher depression (B = 3.24, 95% CI = 1.06, 5.41) and lower life satisfaction (B = −4.54, 95% CI= −8.79, −0.28).

Conclusion

This pilot study indicates that SCI providers are susceptible to implicit racial bias and provides preliminary evidence that greater implicit racial bias of physicians is associated with poorer psychosocial health outcomes for individuals with SCI. It demonstrates the feasibility of studying implicit bias among SCI providers and provides guidance for future research on physician bias and patient outcomes.     

The influence of shoulder pain on functional limitation,perceived health,and depressive mood in patients with traumatic paraplegia

Objective

To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain.

Design

Cross sectional and comparative investigation using the unified questionnaire.

Setting

Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan.

Participants

Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously).

Outcome measures

Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale.

Results

Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r = 0.278, P = 0.017) and lower self-perceived health scores (r = −0.433, P < 0.001) but not SCIM scores (P = 0.342).

Conclusion

Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels.     

Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase

Background

Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments. Cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes.

Objective

Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain.

Study design

Multi-site, double-blind, sham-controlled study.

Participants

Adults with SCI and chronic neuropathic pain at or below the level of injury were randomized to receive active or sham CES.

Intervention

Application of active CES or sham CES 1 hour daily for 21 days. Six-month open-label phase to assess ‘as-needed’ CES use.

Outcome measures

Change in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety pre- to post-treatment.

Results

The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal–Wallis chi-square = 4.70, P < 0.05). During the 21-day trial, there was a significant group × time interaction for only one outcome variable; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did (F = 8.50, P < 0.01, d = 0.59).

Conclusions

On average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects. Individual results varied from no pain relief to a great deal of relief.     

Effects of compression stockings on sympathetic activity and heart rate variability in individuals with spinal cord injury

Objective

To investigate whether wearing graduated compression stockings (GCS) could affect the sympatho-adrenergic and heart rate variability (HRV) responses at rest and after a strenuous wheelchair exercise in individuals with spinal cord injury (SCI).

Design

Crossover trial.

Setting

Department of Physical Medicine and Rehabilitation, Saint Etienne, France.

Participants

Nine men with SCI (five with low paraplegia: LP, four with high paraplegia: HP).

Interventions

Two maximal wheelchair exercise tests: with and without GCS (21 mmHg).

Main outcome measures

HRV measurements: high frequency (HF), low frequency (LF), and LF/HF ratio. Norepinephrine (NOR) and epinephrine (EPI), at rest and post-exercise. Secondary measures were: blood pressure, heart rate, maximal power output, oxygen uptake, stroke volume, cardiac output, at rest, during and after exercise.

Results

When wearing GCS: LFnu_wavelet-post significantly increased and HFnu_wavelet-post significantly decreased (P < 0.05) in SCI subjects, leading to an enhance ratio of LF_wavelet/HF_wavelet and a significantly increased in NOR_rest (P < 0.05).

Conclusions

GCS induces an enhanced sympathetic activity in individuals with paraplegia, regardless of the level of the injury. Enhanced post-exercise sympathetic activity with GCS may help prevent orthostatic hypotension or post-exercise hypotension.     

Body composition modifications in people with chronic spinal cord injury after supervised physical activity

Background

Quantification of body composition variables is important for planning of better activities in relation to individuals with spinal cord injury (SCI).

Objectives

(1) To evaluate changes in body composition in patients with SCI after a supervised physical activity process; (2) To correlate total body fat with time since injury.

Design

Pre-post intervention.

Setting

Sarah Rehabilitation Hospital Network, Brazil.

Participants

Fifty-three men with SCI aged 18–52 years with duration of injury >3 years.

Interventions

The subjects were divided into three groups: tetraplegia (TT) (C5–C8), high paraplegia (HP) (T1–T6), and low paraplegia (LP) (T7–L2). Body composition was estimated in the first and last weeks of hospitalization.

Outcome measures

Body weight (kg), skinfolds sum (mm), absolute (kg), and relative (%) fat and lean body mass.

Results

Body weight increased in TT and decreased in HP (0.8 kg, 95%CI 0.1–1.5; and −1.0 kg, 95%CI −2.0 to 0.0, respectively; P < 0.05). Skinfolds sum decreased only in HP (−13.1 mm, 95%CI −20.7 to −5.5; P < 0.05). Absolute and relative body fat decreased significantly in the paraplegia groups. Lean body mass (LBM) percentage increased significantly in the paraplegia groups. Absolute LBM increased in TT and LP (0.8 kg, 95%CI 0.3–1.3; and 1.3 kg, 95%CI 0.8 to 1.8, respectively; P < 0.05). There was no correlation between time since injury and skinfolds sum for the three groups (P < 0.05).

Conclusion

TT, HP, and LP demonstrated favorable changes in body composition after 29 days of supervised physical activity. However, these changes were different in direction and magnitude.     

The Weil osteotomy for correction of the severe rheumatoid forefoot

Purpose

In rheumatoid arthritis the metatarsophalangeal (MTP) joints are predominantly affected with resultant metatarsalgia and dislocation. Therapy options include many different surgical procedures with results that are not always satisfying. We present the oblique Weil metatarsal osteotomy as a treatment option for the rheumatic forefoot.

Methods

A total of 216 osteotomies in 63 consecutive patients (72 feet) with a mean age at the time of surgery of 59.3 years and long-standing rheumatoid arthritis were observed prospectively for an average of 57.4 months (minimum 36 months). All patients received a Weil osteotomy of the lesser metatarsals with at least one additional procedure of the forefoot. Patients were evaluated prospectively for clinical outcome by the American Orthopaedic Foot and Ankle Society (AOFAS) lesser MTP-interphalangeal scale and subjective satisfaction. In the radiological evaluation weight-bearing X-rays were analysed for alignment, shortening and union.

Results

American Orthopaedic Foot and Ankle Society score increased significantly from 21.9 ± 6.7 to 63.3 ± 9.8 (p < 0.05). The increase was significant for all subgroups regarding pain, function and alignment. All joints were dorsally dislocated preoperatively; a subluxation was present in 13.6 % at follow-up. There was a significant decrease of callositas in 82 %, a decrease in need for orthopaedic shoes in 61 %, a decrease of MTP joint stiffness in 96 % and a relief of severe pain in 97 % of all patients. No metatarsal head dislocation or necrosis, pseudoarthrosis or screw perforation was observed. Of 63 patients, 55 (88 %) subjectively reported excellent or good results.

Conclusions

We conclude that the Weil procedure for lesser metatarsals is a satisfactory method for correcting the rheumatic forefoot and can be recommended as an approach for the future.     

Trunk strength and function using the multidirectional reach distance in individuals with non-traumatic spinal cord injury

Context

Trunk control is essential to engage in activities of daily living. Measuring trunk strength and function in persons with spinal cord injury (SCI) is difficult. Trunk function has not been studied in non-traumatic SCI (NTSCI).

Objectives

To characterize changes in trunk strength and seated functional reach in individuals with NTSCI during inpatient rehabilitation. To determine if trunk strength and seated reach differ between walkers and wheelchair users. To explore relationships between trunk and hip strength and seated functional reach.

Design

Observational study.

Setting

Two SCI rehabilitation facilities.

Participants

32 subacute inpatients (mean age 48.0 ± 15.4 years).

Outcome measures

Isometric strength of trunk and hip and function (Multidirectional Reach Test: MDRT) were assessed at admission and within 2 weeks of discharge. Analysis of variance was conducted for admission measures (MDRT, hip and trunk strength) between walkers and wheelchair users. Changes in MDRT, hip and trunk strength were evaluated using parametric and non-parametric statistics. The level of association between changes in values of MRDT and strength was also examined.

Results

Significant differences between walkers and wheelchair users were found for strength measures (P < 0.05) but not for MDRT. Left- and right-sided reaches increased in wheelchair users only (P < 0.05). Associations between changes in hip strength, trunk strength, and reach distance were found (R = 0.67–0.73).

Conclusion

In clinical settings, it is feasible and relevant to assess trunk, hip strength, and MRDT. Future studies require strategies to increase the number of participants assessed, in order to inform clinicians about relevant rehabilitation interventions.     

Comparison of wire and disc leads to activate the expiratory muscles in dogs

Objective

Respiratory complications account for a major cause of morbidity and mortality in subjects with spinal cord injury (SCI) due to paralysis of the expiratory muscles and the consequent inability to generate effective cough. We demonstrated previously that effective cough can be restored in SCI via spinal cord stimulation (SCS) with disc leads positioned on the lower thoracic and upper lumbar spinal cord via laminotomy incisions. In this study, the effectiveness of wire leads, which can be placed using minimally invasive techniques, to activate the expiratory muscles was evaluated.

Design

Animal study.

Setting

Research laboratory.

Animals

Dogs (n = 8).

Interventions

In separate trials, disc and wire leads were inserted onto the dorsal epidural space at the T9, T11, and L1 spinal cord levels. Effects of electrical stimulation with disc, single wire, and two wire leads placed in parallel were compared.

Outcome measures

Airway pressure generation following stimulation with disc and various configurations of wire leads were compared.

Results

Several different configurations of wire leads resulted in airway pressures that were similar to those generated with monopolar stimulation with disc leads (MSDLs). For example, combined monopolar stimulation with parallel wire leads at the T9 + T11 and T9 + L1 levels resulted in airway pressures that were 103.5 ± 6.4 and 101.9 ± 7.0%, respectively, of those achieved with MSDL. Bipolar stimulation with parallel wire leads at T9–T11 and T9–L1 resulted in airway pressures that were 94.2 ± 3.4 and 96.8 ± 5.0%, respectively, of the pressures achieved with MSDL. Other wire configurations were also evaluated, but were generally less effective.

Conclusion

These results suggest that specific configurations of wire leads, which can be placed via minimally invasive techniques, result in comparable activation of the expiratory muscles compared to disc leads and may be a useful technique to restore cough in persons with SCI.     

Ministernotomy for aortic valve replacement: a study of the preliminary experience.

Objective

The aim of the study was to evaluate the technical feasibility and the postoperative course of aortic valve replacement through a ministernotomy.

Setting

The Montreal Heart Institute and the Hôpital Lariboisière, Paris, France.

Design

A case series from 2 institutions.

Patients

Fifty-one patients who underwent aortic valve replacement through a ministernotomy. The sternal incision was started at the level of the sternal notch extending down to the third or fourth intercostal space with a transverse section of the sternum at this level on both sides or limited to the right side (inverted T or L incision). Thirty-nine patients had aortic stenoses, 6 patients were operated for aortic insufficiency and 6 had mixed disease. The mean (and standard deviation) preoperative left ventricular ejection fraction was 0.56 (0.17).

Main outcome measures

Cardiac bypass time, complications and outcome.

Results

The patients received Carbomedics and St. Jude mechanical valves, Hancock and Carpentier–Edwards bioprostheses. Thirty-eight patients were administered antegrade and retrograde cardioplegia, 10 patients ante-grade and 3 retrograde blood cardioplegia only. The mean (and standard error) cardiopulmonary bypass time and aortic cross-clamp time were 104 (38) minutes and 72 (16) minutes respectively. Two patients (4%) died and 2 patients (4%) showed evidence of a stroke after the procedure. Hospital stay averaged 8 (5) days.

Conclusion

We conclude that aortic valve replacement can be done through a ministernotomy approach with perioperative results similar to those obtained through a conventional sternotomy.     

Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β

Background

Matrix metalloproteinases are catabolic enzymes that play a key role in the articular cartilage degeneration evident in degenerative and inflammatory conditions of articular cartilage. The aim of this study is to assess the ability of pravastatin to modify matrix metalloproteinase (MMP) messenger RNA (mRNA) expression and enzyme activity in a culture of normal human chondrocytes stimulated by interleukin-1β.

Materials and methods

Normal human chondrocytes were stimulated with interleukin (IL)-1β for 6 h to induce MMP expression, simulating a catabolic state, and then treated with pravastatin (1, 5 and 10 μM) for a further 18 h before cell lysates and supernatants were harvested. Cells stimulated with IL-1β but not treated with pravastatin served as controls. Real-time polymerase chain reaction (PCR) was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Statistical analysis was performed using analysis of variance (ANOVA).

Results

MMP-3 and MMP-9 mRNA expression was reduced at all concentrations tested with statistically significant trends in reduction (p = 0.002 and <0.001, respectively). Analysis of culture supernatants revealed that pravastatin treatment led to a reduction in total MMP activity but not to a statistically significant degree (p = 0.07).

Conclusions

Treatment with pravastatin of stimulated human chondrocytes leads to significant down-regulation of selected MMP genes and a non-significant reduction in MMP enzyme activity. Our results provide further evidence that statins may have a role to play in future treatment of disease affecting articular chondrocytes.