CCL22 is a biomarker of cartilage injury and plays a functional role in chondrocyte apoptosis.

BACKGROUND: Osteoarthritis (OA) is one of the leading causes of disability worldwide. Previous history of knee injury is a significant risk factor for OA. It has been established that low-level chronic inflammation plays a pivotal role in the onset and pathogenesis of OA. The primary aim of this research was to determine if a history of knee joint injury is associated with systemic inflammation. A secondary aim was to determine if systemic inflammation is related to knee pain and joint structure. METHODS: Differences in serum cytokine association networks, knee joint structural changes (MRI), and self-reported pain (i.e., Knee Injury and Osteoarthritis Outcome Score Pain subscale, KOOSPAIN and Intermittent and Constant Osteoarthritis Pain score, ICOAP) between individuals who had sustained a youth (aged 15-26 years) sport-related knee injury 3-10 years previously and age- and sex-matched controls were examined. Proteins of interest were also examined in an OA rat model. RESULTS: Cytokine association networks were found to differ significantly between study groups, yet no significant associations were found between networks and KOOSPAIN or MRI-defined OA. A group of cytokines (MCP1/CCL2, CCL22 and TNFα) were differentially associated with other cytokines between study groups. In a pre-clinical rat OA model, serum CCL22 levels were associated with pain (r = 0.255, p = 0.045) and structural changes to the cartilage. CCL22 expression was also observed in human OA cartilage and furthermore, CCL22 induced apoptosis of isolated human chondrocytes. DISCUSSION: These results suggest that CCL22 may be an early factor in the onset/pathogenic process of cartilage degeneration and/or related to pain OA.

Female sexual function varies over time and is dependent on partner-specific factors: a population-based longitudinal analysis of six sexual function domains.

BACKGROUND: Most studies examining female sexual functions (FSFs) have used cross-sectional designs, not allowing for studying temporal stability and possible relationships between different FSFs over time. Our aim was to study these relationships using a longitudinal approach. METHOD: The study sample consisted of 2173 Finnish women from two large-scale, population-based data collections 7 years apart. The Female Sexual Function Index was used. Analyses were further conducted separately for women in different relationship constellations. RESULTS: Standardized autoregressive paths ranged from 0.136 (sexual satisfaction) to 0.447 (orgasm function) in the full sample, suggesting that most of the variance in FSF was explained by something other than previous function. Orgasm, desire and satisfaction were the strongest predictors of other functions in the full sample and for women in the same relationship at both time points (higher orgasm function predicted higher function in other domains; greater sexual desire and satisfaction predicted lower function in other domains), however, with small effects sizes. For single women, orgasm function and sexual desire were the only significant autoregressive paths. Significant unidirectional cross-domain paths were found for women in the same relationship at both time points. One significant cross-domain path, not confirmed as unidirectional, was found for single women. CONCLUSIONS: FSFs varied considerably over 7 years and relationship status was of importance when assessing temporal stability and cross-domain effects. Our results advocate tailored psychobehavioural treatment interventions for female sexual dysfunctions that take partner-specific factors into account.

Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data.

BACKGROUND: Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. METHOD: We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. RESULTS: We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). CONCLUSIONS: Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

Antidepressant use and work-related injuries.

BACKGROUND: Adverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use. METHOD: Antidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design). RESULTS: In 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10-1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08-1.83). CONCLUSIONS: Antidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury.

Evaluation of HLA-DRB1 imputation using a Finnish dataset.

Owing to the vast amount of alleles, high-resolution human leukocyte antigen (HLA) typing is expensive and time-consuming. Scientists have attempted to develop computational approaches to define HLA alleles with high confidence. We tested the reliability of HLA*IMP and SNP2HLA for imputing HLA-DRB1 alleles in a Finnish material (n=161). The per-individual success rates varied between 16.68% and 25.4% using both softwares. One of the most prominent example was HLA-DRB1*01:01 allele showing approximately a 30% success rate while being the most common wrongly imputed allele. In Finland, isolation and migration history have shaped the gene pool narrower showing HLA haplotype frequencies typical to the Finnish population when compared to Europeans. The imputation success for HLA-DRB1 alleles was very low pointing to the importance of population-specific reference material.

Job strain and the risk of severe asthma exacerbations: a meta-analysis of individual-participant data from 100 000 European men and women.

BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). CONCLUSIONS: Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene.

We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. We find no evidence of YRRM genes, recently proposed as AZF candidates, in the AZF region. The region contains a single-copy gene, DAZ (Deleted in AZoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein. The possibility that DAZ is AZF should now be explored.

Prolonged immobilization compromises up-regulation of repair genes after tendon rupture in a rat model.

It was hypothesized that mobilization vs immobilization after injury would promote tissue healing by regulating gene expression for molecules associated with repair. Cast immobilization vs free mobilization was studied after rat Achilles tendon rupture. Reverse transcriptase-polymerase chain reaction was performed at 8 and 17 days post-rupture to assess different growth factors [brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1)] and inflammatory mediators [cyclooxygenase 1 and 2 (COX 1 and COX 2), inducible nitric oxide synthase and hypoxia-inducible factor-1alpha (HIF-1alpha)] in the healing region. At 8 days post-injury, tendon mRNA levels were comparable in both groups. However, by day 17, the mRNA levels for BDNF, bFGF, COX 1 and HIF-1alpha in the mobilized group had increased significantly. Corresponding mRNA levels in the immobilized group decreased during the same period. There were no significant differences in the expression of NGF, IGF-1 or COX 2 between the different groups, indicating that injury-associated expression of these molecules is not overtly influenced by loading. This study supports the notion that prolonged immobilization post-rupture hampers the healing process by compromising the up-regulation of repair gene expression in the healing tendon. It might be speculated that a shorter period of immobilization, i.e. 1 week, would not impair the healing process significantly. The findings support the current development of earlier and more active rehabilitation programs after tendon injuries.

Antidepressant treatment among social workers, human service professionals, and non-human service professionals: A multi-cohort study in Finland, Sweden and Denmark.

BACKGROUND: Social workers have an elevated risk for mental disorders, but little is known about their antidepressant treatment. AIMS: To examine any and long-term antidepressant treatment among social workers in Finland, Sweden and Denmark. METHODS: We linked records from drug prescription registers to three prospective cohorts: the Finnish Public Sector study, years 2006-2011, and nation-wide cohorts in Sweden and Denmark, years 2006-2014, including a total of 1.5 million employees in (1) social work, (2) other social and health care professions, (3) education and (4) office work. We used Cox proportional hazards models to estimate hazard ratios for any and long-term (>6 months) antidepressant treatment among social workers compared to the three reference occupational groups and carried out meta-analyses. RESULTS: During follow-up, 25% of social workers had any prescriptions for antidepressants (19-24% reference occupations) and 20% for long-term treatment (14-19% reference occupations). The pooled effects for any and long-term treatment showed that probabilities were 10% higher in social workers compared to other health and social care professionals and 30% higher compared to education and non-human service professionals. Probabilities for any treatment in the three countries were relatively similar, but for long-term treatment social workers in Finland had a greater risk compared with other human service professions. LIMITATIONS: There were differences between the cohorts in the availability of data. Specific diagnoses for the antidepressant treatment were not known neither adherence to treatment. CONCLUSION: Social workers have a higher risk for any and long-term antidepressant treatment than other human and non-human service professionals.

Carotid artery compliance in users of plant stanol ester margarine.

OBJECTIVE: To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. DESIGN: Case-control study comparing regular stanol ester margarine users to non-users. SETTING: Occupational health service clinic. SUBJECTS: We recruited 50 cases and 50 controls (mean age 51+/-8, range 26-65 years). All subjects were non-smokers and the study groups were matched for age and sex. As cases, we invited subjects who had been using regularly (daily) plant stanol ester margarine for a period of 2 years or longer. Non-invasive ultrasound was used to measure carotid artery compliance, carotid intima-media thickness and brachial artery flow-mediated endothelial dependent vasodilatation. RESULTS: The carotid artery compliance was non-significantly higher in cases compared with controls, 1.84+/-1.02 vs 1.58+/-0.76 %/10 mm Hg (P=0.13). The difference in compliance became statistically significant (P=0.04) when the unbalance between the groups in family history of coronary artery disease and years of education were taken into account. There was also a significant dose-response relationship between stanol margarine use and carotid compliance, longer use being associated with higher compliance. Serum lipoproteins, blood pressure, flow-mediated dilation and intima-media thickness values did not differ between cases and controls. CONCLUSION: These data raise the possibility that regular stanol ester margarine use may be associated with beneficial changes in arterial compliance. Intervention studies are needed to test this hypothesis and to reveal possible mechanisms.

High prevalence of noise following Delta ceramic-on-ceramic total hip arthroplasty.

AIMS: We evaluated the short-term functional outcome and prevalence of bearing-specific generation of audible noise in 301 patients (336 hips) operated on with fourth generation (Delta) medium diameter head, ceramic-on-ceramic (CoC) total hip arthroplasties (THAs). PATIENTS AND METHODS: There were 191 female (63%) and 110 male patients (37%) with a mean age of 61 years (29 to 78) and mean follow-up of 2.1 years (1.3 to 3.4). Patients completed three questionnaires: Oxford Hip Score (OHS), Research and Development 36-item health survey (RAND-36) and a noise-specific symptom questionnaire. Plain radiographs were also analysed. A total of three hips (0.9%) were revised. RESULTS: There were 52 patients (54 hips, 17%) who reported noise, and in 25 (48%) of them the noise was frequently heard. In the multiple regression analysis, the only independent risk factor for noise was a specific THA brand, with a threefold increased risk (95% confidence intervals 1.39 to 6.45, p = 0.005) of noise compared with the reference THA brand. Patients with noisy hips had lower median OHS (43 versus 46.5, p = 0.002) and their physical functioning (p = 0.021) subscale in RAND-36 was reduced. CONCLUSION: Noise was surprisingly common in this population. Cite this article: Bone Joint J 2017;99-B:44-50.

Trends in work disability with mental diagnoses among social workers in Finland and Sweden in 2005-2012.

Aims Social workers report high levels of stress and have an increased risk for hospitalisation with mental diagnoses. However, it is not known whether the risk of work disability with mental diagnoses is higher among social workers compared with other human service professionals. We analysed trends in work disability (sickness absence and disability pension) with mental diagnoses and return to work (RTW) in 2005-2012 among social workers in Finland and Sweden, comparing with such trends in preschool teachers, special education teachers and psychologists. METHODS: Records of work disability (>14 days) with mental diagnoses (ICD-10 codes F00-F99) from nationwide health registers were linked to two prospective cohort projects: the Finnish Public Sector study, years 2005-2011 and the Insurance Medicine All Sweden database, years 2005-2012. The Finnish sample comprised 4849 employees and the Swedish 119 219 employees covering four occupations: social workers (Finland 1155/Sweden 23 704), preschool teachers (2419/74 785), special education teachers (832/14 004) and psychologists (443/6726). The reference occupations were comparable regarding educational level. Risk of work disability was analysed with negative binomial regression and RTW with Cox proportional hazards. RESULTS: Social workers in Finland and Sweden had a higher risk of work disability with mental diagnoses compared with preschool teachers and special education teachers (rate ratios (RR) 1.43-1.91), after adjustment for age and sex. In Sweden, but not in Finland, social workers also had higher work disability risk than psychologists (RR 1.52; 95% confidence interval 1.28-1.81). In Sweden, in the final model special education teachers had a 9% higher probability RTW than social workers. In Sweden, in the final model the risks for work disability with depression diagnoses and stress-related disorder diagnoses were similar to the risk with all mental diagnoses (RR 1.40-1.77), and the probability of RTW was 6% higher in preschool teachers after work disability with depression diagnoses and 9% higher in special education teachers after work disability with stress-related disorder diagnoses compared with social workers. CONCLUSION: Social workers appear to be at a greater risk of work disability with mental diagnoses compared with other human service professionals in Finland and Sweden. It remains to be studied whether the higher risk is due to selection of vulnerable employees to social work or the effect of work-related stress in social work. Further studies should focus on these mechanisms and the risk of work disability with mental diagnoses among human service professionals.

Effects of low-fat hard cheese enriched with plant stanol esters on serum lipids and apolipoprotein B in mildly hypercholesterolaemic subjects.

OBJECTIVE: To investigate the cholesterol-lowering effects of a low-fat cheese enriched with plant stanol esters in mildly hypercholesterolaemic subjects, as part of their normal diet. DESIGN: A randomized double-blind parallel-group study. SETTING: Valio Ltd, Helsinki. SUBJECTS: Sixty-seven mildly hypercholesterolaemic volunteers (24 men, 43 women) participated in the study, which all of them completed. INTERVENTIONS: The subjects were randomly assigned to the plant stanol ester group or the control group. During the 5-week intervention, the subjects in the stanol group consumed a cheese enriched with 2 g of plant stanols per day, and the subjects in the control group, a control cheese with no plant stanols. RESULTS: In the stanol ester group, as compared to the control group, both serum total and low-density lipoprotein (LDL) cholesterol decreased significantly, that is, by 5.8% (-0.32 mmol/l, 95% CI -0.50 to -0.15 mmol/l, P < 0.001) and 10.3% (-0.36 mmol/l, 95% CI -0.53 to -0.18 mmol/l, P < 0.001), respectively. There were no significant changes in high-density lipoprotein cholesterol (HDL), triglycerides or apolipoprotein B concentrations between the groups. CONCLUSION: Cheese enriched with 2 g of plant stanol in the form of fatty acid esters decreases serum total and LDL cholesterol significantly.

Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro.

Proteoglycan 4 (PRG4/lubricin) is secreted by cells that reside in articular cartilage and line the synovial joint. Lubricin may play a role in modulating inflammatory responses through interaction with CD44. This led us to examine if lubricin could be playing a larger role in the modulation of inflammation/immunity through interaction with Toll-like receptors (TLRs). Human Embryonic Kidney (HEK) cells overexpressing TLRs 2, 4 or 5 and surface plasmon resonance were employed to determine if full length recombinant human lubricin was able to bind to and activate TLRs. Primary human synovial fibroblasts were also examined using flow cytometry and Luminex multiplex ELISA. A rat destabilization model of osteoarthritis (OA) was used to determine if lubricin injections were able to regulate pain and/or inflammation in vivo. Lubricin can bind to and regulate the activity of TLRs, leading to downstream changes in inflammatory signalling independent of HA. We confirmed these findings in vivo through intra-articular injections of lubricin in a rat OA model where the inhibition of systemic inflammatory signaling and reduction in pain were observed. Lubricin plays an important role in regulating the inflammatory environment under both homeostatic and tissue injury states.

Effects of prospective, randomized cholesterol-lowering dietary intervention and apolipoprotein E phenotype on serum lipoprotein(a) concentrations of infants aged 7-24 mo.

A high serum lipoprotein(a) [Lp(a)] concentration is associated with increased risk of coronary artery disease. Few external factors are able to markedly modify serum Lp(a) concentrations. The aim of this study was to evaluate how serum Lp(a) concentrations of infants between 7 and 24 mo of age change in a cholesterol-lowering dietary intervention, and to assess the influence of apolipoprotein (apo) E phenotypes on serum Lp(a) concentrations. The intervention children (n=394) had serum cholesterol, non-high-density-lipoprotein cholesterol, and cholesterol corrected for Lp(a)-cholesterol values (P for all <0.001) lower than those of the control children (n=390), but median serum Lp(a) concentrations at the age of 24 mo were not different from those of control children. Serum Lp(a) values differed according to the apo E phenotype as the median Lp(a) values increased from E2/2 to E3/2, E4/2, E3/3, E4/3, and to E4/4 (P for the difference=0.023, Mann-Whitney U test). Our results suggest that apo E phenotype influences serum Lp(a) concentrations noticeably, but the effect of the cholesterol-lowering dietary intervention was not significant in subjects aged 24 mo.

Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP).

BACKGROUND: Introducing nutritional and lifestyle principles to children in late infancy may permanently improve their adherence to a low-saturated fat, low-cholesterol diet, thus reducing of coronary risk factors, but worries about possible effects on growth and development have hampered such an approach. OBJECTIVE: The Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP) aimed to decrease exposure to known environmental atherosclerosis risk factors in children 7-36 mo of age. DESIGN: Repeated, individualized counseling aimed at promoting a fat intake of 30% of energy and a 1:1:1 ratio of saturated to monounsaturated to polyunsaturated fat intake was provided (n = 540 intervention children; 284 boys). Nutrition was discussed superficially with the families of the control children (n = 522; 266 boys) and food intake was recorded at 3-6-mo intervals by use of 3-4-d food diaries. Serum lipids were measured at 6-12-mo intervals and growth was monitored regularly. RESULTS: Fat intake of the intervention (control) children provided 29.5% (29.4%) of energy at the age of 8 mo, 26.6% (28.5%) of energy at 13 mo, 30.5% (33.5%) of energy at 24 mo, and 31. 5% (33.5%) of energy at 36 mo. The intervention children consistently consumed less saturated fat than did the control children (P: <0.0001). Recommended intakes of other nutrients (except vitamin D and occasionally iron) were reached irrespective of the amount and type of dietary fat. Serum cholesterol, non-HDL cholesterol, and HDL-cholesterol concentrations were 3-6% lower in the intervention children than in the control children. The intervention had no effect on height, weight, or head circumference gain. Fat intake did not predict children's growth patterns. CONCLUSION: Repeated, individualized counseling in early childhood aimed at reducing consumption of saturated fat and cholesterol was effective and feasible and did not restrict growth in circumstances in which children were regularly monitored.

Detection of Pneumococcus from whole blood, buffy coat and serum samples by PCR during bacteremia in mice.

Whole blood, purified leukocyte fraction and serum were investigated as specimens for the detection of pneumococcal bacteremia by polymerase chain reaction (PCR) in mice. The PCR findings were compared to the blood culture results. Samples were taken from animals 3 and 12 h after intraperitoneal bacterial challenge. The pneumococcal culture was positive in 27% and 77% of blood samples at 3 and 12 h after challenge, respectively. All whole blood samples were positive by PCR at both time points. Of the buffy coat samples, two of the three pools were PCR-positive at 3 h and all pools at 12 h after bacterial challenge. In the serum sample group, only 40% of the sera were PCR-positive at 3 h, while at 12 h 90% of the samples were PCR-positive. According to these results, whole blood seems to be the best specimen for the detection of pneumococcal DNA by PCR in bacteremic mice.

Pneumococcal capsular antigen detection after enrichment culture: an alternative to culture methods in epidemiologic research.

Bacterial culture of Streptococcus pneumoniae followed by serotyping is not always feasible under field conditions. Antigen detection methods could be an alternative, but they are associated with sensitivity problems. In an effort to improve their sensitivity, we introduced an enrichment phase before antigen detection and compared the results with direct bacterial culture, using nasopharyngeal swabs from 95 children with symptoms of acute respiratory infection. Antigen detection was performed by latex agglutination and counterimmunoelectrophoresis. Streptococcus pneumoniae was found in 29 (30%) of the samples by culture, and in 42 (44%) by antigen detection after enrichment, an excess of 45% over culture findings. This excess was shown to represent true positive samples since pneumococcal DNA could be detected by polymerase chain reaction in all 15 antigen-positive, culture-negative samples. Two culture-positive samples were antigen-negative; in one of these the bacteria were nonencapsulated. We conclude that for type-specific demonstration of S. pneumoniae, detection of pneumococcal antigen after an enrichment step is a sensitive method that can be applied for epidemiologic study purposes, e.g., in vaccine trials, in areas without ready access to a good microbiology laboratory.

Transmitter synthesis increases in substantia nigra neurons of the aged mouse.

Striatal dopamine concentrations are relatively well maintained with age despite extensive death of the nigrostriatal neurons whose terminals contain the dopamine. Counts of nigrostriatal dopaminergic neurons in C57BL mice identified using immunocytochemistry, Fluoro-Gold retrograde axonal transport and Nissl staining were combined with measures of striatal dopamine and DOPA after saline, pargyline or NSD-1015 treatment. On average, 68% of the dopaminergic nigrostriatal neurons died between ages 8 and 104 weeks and there was a 3-fold increase in dopamine synthesis per average neuron in the aged mice. Increased transmitter synthesis by surviving neurons may serve to compensate brain function in old age.

Selective ablation of rat knee joint innervation with injected immunotoxin: a potential new model for the study of neuropathic arthritis.

Neuropathic arthropathy is a severe chronic degenerative condition associated with decreased or absent sensory innervation of the involved joint. Existing animal models of neuropathic arthritis are limited by the technical difficulties of obtaining either highly selective or complete joint denervation in a minimally invasive fashion. We undertook experiments to determine the feasibility of using the newly described method of selective neuronal lesioning with injected immunotoxin as a means of creating a more tractable model of neuropathic arthritis. Retrograde tracing with fluorochrome revealed that the knee joint of the female Wistar rat is supplied by 581 +/- 31 (mean +/- SD) joint afferents. Immunohistochemistry confirmed that virtually all sensory neurons in the rat express the cell surface receptor Thy 1. Injection of rat knee joints with an immunotoxin targeted toward Thy 1 resulted in the selective ablation of an average of 88% of the joint afferents identified with fluorochrome that are normally found in the ipsilateral L3 and L4 ganglia.