Which Is Better for Arthroscopic Tenodesis of the Long Head of the Biceps: Soft Tissue or Bony Interference Fixation?

PURPOSE: To compare the outcome between arthroscopic soft tissue tenodesis (STT) at the rotator interval and bony interference fixation tenodesis (BIFT) at the distal bicipital groove for the long head of the biceps (LHB). METHODS: Twenty-five shoulders that underwent arthroscopic STT of the LHB were compared with 28 shoulders that underwent arthroscopic BIFT using a 5.5-mm Bio-Tenodesis screw (Arthrex, Naples, FL). American Shoulder and Elbow Surgeons scores, Constant score, and elbow flexion strength index (EFSI) were checked preoperatively, postoperative 1 year and 2 years. Ultrasound imaging evaluation took place at 1 year and 2 years postoperatively as well. RESULTS: The overall functional outcomes improved after surgery in both groups. The BIFT group showed a significant increase in EFSI (preop: 0.54, postoperative 2 years: 0.94) compared with that of the STT group (preop: 0.52, postoperative 2 years: 0.74) at postoperative 2 years (P = .006). However, no significant difference was seen in the increase of American Shoulder and Elbow Surgeons scores and Constant scores between the two groups. At postoperative 2 years, ultrasound showed seven empty grooves in the STT group, but only two empty grooves in the BIFT group (P = .046). CONCLUSIONS: Arthroscopic BIFT for the LHB showed better improvement in EFSI than arthroscopic STT. In addition, the STT group showed a higher failure rate than the BIFT group. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

The Effect of Denosumab on Rotator Cuff Repair in Women Aged 60 and over with Osteoporosis: A Prospective Observational Study.

BACKGROUND: In previous studies, denosumab, a RANKL human monoclonal antibody used in osteoporosis treatment, has shown efficacy in tendon healing after rotator cuff repair. This prospective study investigated the effects of denosumab on tendon healing, re-tear rates, and clinical outcomes post rotator cuff repair in women with osteoporosis. METHOD: This was a prospective, observational study, employing propensity score matching for the control group. From March 2018 to March 2023, female patients over the age of 60 with normal bone density undergoing arthroscopic rotator cuff repair were selected as controls through propensity score matching (PSM) and compared with female patients of the same age group with osteoporosis who were receiving denosumab treatment. The control group was matched using 1-to-2 propensity score matching. Radiological examinations and functional outcomes were assessed preoperatively and at 6 months postoperatively. RESULTS: In the final analysis, the study comprised 34 patients in the denosumab treatment group (Group 1) and 68 patients in the control group (Group 2). The functional scores showed significant improvement at 6 months post-surgery in both groups. No significant difference in the functional scores was observed among the groups. The re-tear rate, defined according to Sugaya's classification (types IV and V) as re-tear, was slightly higher in Group 1 at 16.7% (6 of 34) compared to Group 2 at 11.7% (8 of 68), but the difference was not statistically significant (p = 0.469). The re-tear patterns, classified according to Rhee's classification, also showed no significant difference among the groups (Group 1: 2/4 of 6; Group 2: 4/4 of 8; p = 0.571). The occurrence of type I re-tear exhibited no significant difference between the two groups (5.9% vs. 5.9%; p = 1.000). CONCLUSIONS: The administration of denosumab following arthroscopic rotator cuff repair in women aged 60 and over with osteoporosis resulted in a re-tear rate that was similar to that observed in patients without osteoporosis. This result suggests that denosumab administration might be beneficial for rotator cuff healing, particularly in the context of osteoporosis, a known risk factor for increased retear rates. Therefore, comprehensive osteoporosis screening and treatment should be considered in conjunction with rotator cuff repair surgery in middle-aged women.

Reinforcement Techniques in Arthroscopic Repair of Large-to-Massive Rotator Cuff Tears: A Comparative Study of Superior Capsule Reconstruction and Patch Graft Augmentation.

Background: Large-to-massive rotator cuff tears (LMRCTs) present challenges in achieving successful repair due to factors such as muscle atrophy and tendon retraction. Arthroscopic rotator cuff repair (ARCR) with reinforcement techniques like superior capsule reconstruction (SCR) or patch graft augmentation (PGA) has emerged as a less invasive option to improve shoulder joint stability and prevent retear. This study aimed to compare the clinical and radiological outcomes of SCR and PGA as reinforcement techniques for the arthroscopic repair of LMRCTs. Methods: A single-center retrospective study was conducted on patients undergoing LMRCT repair between January 2019 and December 2021. Patients were divided into two groups: those receiving SCR (Group 1) and those receiving PGA (Group 2). Various clinical parameters including range of motion, functional scores, and radiological assessments were evaluated preoperatively and six months postoperatively. Results: Both SCR and PGA techniques demonstrated significant improvements in the range of motion and clinical scores postoperatively. However, Group 2 showed higher postoperative SST and UCLA scores compared to Group 1. Radiologically, there was a slightly higher retear rate in Group 2, although this was not statistically significant. Group 2 also had a shorter mean duration of surgery compared to Group 1. Conclusions: In the arthroscopic repair of LMRCTs, both SCR and PGA techniques exhibit favorable clinical and radiological outcomes. Despite the simplicity of PGA compared to SCR, it offers comparable results with a shorter surgical duration, making it a feasible reinforcement option for surgeons.

Doctor shopping trend of patients before undergoing rotator cuff repair in Korea: a multicenter study.

BACKGROUND: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. METHODS: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. RESULTS: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000-5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. CONCLUSIONS: Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment. Level of evidence: IV.

A Comparison of Clinical Outcomes in Rotator Cuff Re-Tear Patients Who Had Either an Arthroscopic Primary Repair or Arthroscopic Patch Augmentation for Large-to-Massive Rotator Cuff Tears.

BACKGROUND AND PURPOSE: Despite the prevalent incidence of re-tear following rotator cuff repair, there is a notable lack of comparative studies investigating the outcomes between patients with re-tear who underwent primary repair versus those who received patch augmentation for large-to-massive tears. We assessed clinical outcomes of these techniques through a retrospective, randomized controlled trial. METHODS: 134 patients diagnosed with large-to-massive rotator cuff tears from 2018 to 2021 underwent surgery; 65 had primary repair and 69 had patch augmentation. A total of 31 patients with re-tears were included, split into two groups; Group A (primary repair, 12 patients) and Group B (patch augmentation, 19 patients). Outcomes were evaluated using several clinical scales and MRI imaging. RESULTS: Most clinical scores improved postoperatively in both groups. No significant difference in clinical outcomes was observed between groups, except for pain visual analog scale (P-VAS) scores. P-VAS scores showed greater decrease in the patch-augmentation group, a statistically significant difference. CONCLUSIONS: for large-to-massive rotator cuff tears, patch augmentation led to greater decreases in pain than primary repair, despite similar radiographic and clinical results. Greater tuberosity coverage of the supraspinatus tendon footprint may impact P-VAS scores.

Concurrent blockade of free radical and microsomal prostaglandin E synthase-1-mediated PGE2 production improves safety and efficacy in a mouse model of amyotrophic lateral sclerosis.

While free radicals and inflammation constitute major routes of neuronal injury occurring in amyotrophic lateral sclerosis (ALS), neither antioxidants nor non-steroidal anti-inflammatory drugs have shown significant efficacy in human clinical trials. We examined the possibility that concurrent blockade of free radicals and prostaglandin E(2) (PGE(2))-mediated inflammation might constitute a safe and effective therapeutic approach to ALS. We have developed 2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobenzoic acid] (AAD-2004) as a derivative of aspirin. AAD-2004 completely removed free radicals at 50 nM as a potent spin-trapping molecule and inhibited microsomal PGE(2) synthase-1 (mPGES-1) activity in response to both lipopolysaccharide-treated BV2 cell with IC(50) of 230 nM and recombinant human mPGES-1 protein with IC(50) of 249 nM in vitro. In superoxide dismutase 1(G93A) transgenic mouse model of ALS, AAD-2004 blocked free radical production, PGE(2) formation, and microglial activation in the spinal cords. As a consequence, AAD-2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD-2004 was superior to riluzole or ibuprofen. Gastric bleeding was not induced by AAD-2004 even at a dose 400-fold higher than that required to obtain maximal therapeutic efficacy in superoxide dismutase 1(G93A). Targeting both mPGES-1-mediated PGE(2) and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases.

Dynamic function of coracoclavicular ligament at different shoulder abduction angles: a study using a 3-dimensional finite element model.

PURPOSE: The aim of this study was to determine the acromioclavicular (AC) motion and change in length and tension of the coracoclavicular ligament during different positions of shoulder abduction using a 3-dimensional finite element model based on computed tomography images from normal human shoulders. METHODS: The right shoulders of 10 living subjects were scanned with a high-resolution computed tomography scanner at 0°, 60°, 120°, and 180° of shoulder abduction. Several modeling programs were used to simulate AC motion. Finite element models of the conoid and trapezoid ligaments were constructed based on each footprint. The tension and length changes of each ligament during shoulder abduction were assessed. RESULTS: The distal clavicle exhibited internal rotation with respect to the medial acromion at 0°, 60°, 120°, and full abduction (3.2° ± 2.9°, 23.2° ± 10.8°, 20.6° ± 3.7°, and 37.1° ± 3.4°, respectively). With horizontal motion, the clavicle translated posteriorly at 60° of abduction (4.4 ± 3.4 mm) and then translated anteriorly at 120° and full abduction (0.4 ± 1.6 mm and 1.9 ± 0.4 mm, respectively). The lengths of the conoid ligament gradually increased at 60° to 180° of shoulder abduction whereas those of the trapezoid ligament remained relatively consistent at 60° to 120° of abduction compared with 0° of abduction. CONCLUSIONS: The distal clavicle had a wide range of motion during shoulder abduction, which did not support the concept of synchronous motion with the scapula. The conoid and trapezoid ligaments functioned reciprocally during shoulder abduction. With increasing shoulder abduction, the length of the conoid ligament gradually increased; meanwhile, the trapezoid ligament was relatively consistent and then lax at full abduction. In particular, the conoid ligament may act as a key restraint to prevent excessive retraction of the scapula during shoulder abduction. CLINICAL RELEVANCE: The data in this study have the potential to suggest that conoid and trapezoid ligaments should be reconstructed separately, and rigid AC fixation in patients with AC separation is not recommended based on the findings of this study.

Symptomatic residual instability with grade II acromioclavicular injury.

PURPOSE: Our objective was to evaluate the effectiveness of arthroscopic distal clavicle resection in cases presenting with pain and subtle instability after neglected grade II acromioclavicular (AC) joint dislocation. METHODS: From February 1998 to May 2006, 17 patients with symptomatic AC instability following chronic grade II AC joint injury were studied. Sixteen patients were male and one female, with a mean age of 48 years. An all-arthroscopic procedure comprising disk removal and distal clavicle resection was performed in all cases. All patients were reviewed clinically, preoperatively and at final follow-up (mean 38 months) using the pain score on a visual analog scale and the Constant score. Strength was measured using an Isobex digital strength analyzer. Patient's personal satisfaction after the procedure was documented as excellent, good or poor. Postoperative AC joint radiographs were routinely obtained in all patients to measure the amount of clavicle resection. RESULTS: Two patients underwent additional reconstructive surgery for disabling pain and dysfunction even after the arthroscopic resection procedure. The remaining 15 patients were analyzed. The pain scores improved significantly (p = 0.03). The mean pain score was 5.8 (range 5-9) before treatment and 1.6 (range 0-3) at follow-up. The Constant scores had improved significantly at the final follow-up (p = 0.001). The median Constant score increased from 46 (range 36-69) preoperatively to 71 (range 48-84) postoperatively. Strength had improved at the last follow-up. Eleven patients were satisfied and six were not satisfied with this procedure at the final follow-up. CONCLUSIONS: Arthroscopic distal clavicle resection statistically improved the pain score, Constant score and strength for grade II AC injury with subtle distal clavicle instability. However, six patients (33.5 %) were not satisfied subjectively. This procedure seemed to be a reasonable initial treatment option with lower morbidity.

Surgical correction for supination loss following malunited radial fractures.

We evaluated fourteen patients who had restricted supination as a major impairment related with a malunited radius fracture. All patients underwent an opening wedge corrective osteotomy, bone grafting, and volar plate fixation. Clinical results were assessed based on range of motion, visual analogue scale for pain, grip power, and a Modified Mayo Wrist Score. The mean supination increased from 24 degrees preoperatively to 71 degrees postoperatively (p < 0.01). Dorsiflexion range, grip power and pain score improved significantly after the operation. The mean value for the Modified Mayo Wrist score improved from 58.6 points to 83.9 points (p < 0.01). Radiological measurements showed that the degree of dorsal angulation decreased from a mean of 9.0 degrees to -2.5 degrees after the corrective osteotomy. This study demonstrated that a malunited radius fracture with dorsal angulation, even if the latter appears mild, can induce functional impairment due to limited range of supination. Supination can be restored by an appropriately performed corrective osteotomy.

The Use of Intravenous Zoledronate May Reduce Retear Rate after Rotator Cuff Repair in Older Female Patients with Osteoporosis: A First In-Human Prospective Study.

The objective of this study was to demonstrate the effect of intravenous (IV) zoledronate administration on rotator cuff healing, retear rate, and clinical outcomes in osteoporotic patients who underwent arthroscopic rotator cuff repair (ARCR) compared with patients with normal bone densities. In this prospective nonrandomized comparative study with propensity score matching, 30 patients who were postoperatively administered IV zoledronate (5 mg) were enrolled as the study group. The control group was matched using 1-to-2 propensity score matching. Radiologic and functional outcomes were evaluated 6 months after surgery. The functional scores in both groups exhibited significant improvement 6 months after surgery. Compared with Group 1 (osteoporosis with IV zoledronate injection) Group 2 (normal bone density) showed significant improvement in their University of California, Los Angeles (UCLA) shoulder score and Constant Shoulder Score (CSS) at 6 months postoperatively. The range of motion improved in both groups at 6 months after surgery. The retear rates according to Sugaya's classification (IV and V) were 13.3% (4 of 30 patients) and 25% (15 of 60 patients) in Groups 1 and 2, respectively, which established a non-inferiority of Group 1 to the control group. The retear pattern according to Rhee's classification in Group 1 was type I in all cases, whereas eight cases of type I and seven cases of type II patterns were observed in Group 2, which was statistically insignificant between the groups. In conclusion, anti-osteoporotic drug use is beneficial for patients with osteoporosis to reduce the failure rate after an ARCR of length > 2 cm, especially in older female patients. Moreover, thorough scrutiny is required to detect osteoporosis in patients with rotator cuff tears, especially in female patients.

Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice.

BACKGROUND: Evidence suggests that rheumatoid arthritis (RA) may enhance or reduce the progression of Alzheimer's disease (AD). The present study was performed to directly explore the effects of collagen-induced rheumatoid arthritis (CIA) on amyloid plaque formation, microglial activation, and microvascular pathology in the cortex and hippocampus of the double transgenic APP/PS1 mouse model for AD. Wild-type or APP/PS1 mice that received type II collagen (CII) in complete Freund's adjuvant (CFA) at 2 months of age revealed characteristics of RA, such as joint swelling, synovitis, and cartilage and bone degradation 4 months later. Joint pathology was accompanied by sustained induction of IL-1ß and TNF-α in plasma over 4 weeks after administration of CII in CFA. RESULTS: CIA reduced levels of soluble and insoluble amyloid beta (Aß) peptides and amyloid plaque formation in the cortex and hippocampus of APP/PS1 mice, which correlated with increased blood brain barrier disruption, Iba-1-positive microglia, and CD45-positive microglia/macrophages. In contrast, CIA reduced vessel density and length with features of microvascular pathology, including vascular segments, thinner vessels, and atrophic string vessels. CONCLUSIONS: The present findings suggest that RA may exert beneficial effects against Aß burden and harmful effects on microvascular pathology in AD.

Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat.

Abnormal brain iron homeostasis has been proposed as a pathological event leading to oxidative stress and neuronal injury under pathological conditions. We examined the possibility that neuronal iron overload would mediate free radical production and delayed neuronal death (DND) in hippocampal CA1 area after transient forebrain ischemia (TFI). Mitochondrial free radicals (MFR) were biphasically generated in CA1 neurons 0.5-8 and 48-60 h after TFI. Treatment with Neu2000, a potent spin trapping molecule, as well as trolox, a vitamin E analogue, blocked the biphasic MFR production and attenuated DND in the CA1, regardless of whether it was administered immediately or even 24 h after reperfusion. The late increase in MFR was accompanied by iron accumulation and blocked by the administration of deferoxamine-an iron chelator. Iron accumulation was attributable to prolonged upregulation of the transferrin receptor and to increased uptake of peripheral iron through a leaky blood-brain barrier. Infiltration of iron-containing cells and iron accumulation were attenuated by depletion of circulating blood cells through X-ray irradiation of the whole body except the head. The present findings suggest that excessive iron transported from blood mediates slowly evolving oxidative stress and neuronal death in CA1 after TFI, and that targeting iron-mediated oxidative stress holds extended therapeutic time window against an ischemic event.

Calcific tendinitis of the shoulder in the Korean population: demographics and its relation with coexisting rotator cuff tear.

BACKGROUND: To evaluate the demographics, clinical and radiographic features of calcific tendinitis of the shoulder in the Korean population, specifically focusing on the incidence of coexisting rotator cuff tear. METHODS: Between October 2014 and January 2015, we performed a prospective multicenter study with 506 patients from 11 training hospitals in Korea. We collected data of demographics and radiographic analysis based on simple radiographs, clinical assessments based on visual analog scale (VAS) and the American Shoulder Elbow Surgeons (ASES) score, and treatment modalities that are used currently. We also evaluated coexisting rotator cuff tear by ultrasonography (US) or magnetic resonance imaging (MRI) images. RESULTS: There were 402 female patients (79%) with mean age of 55 years (range, 31-87 years). Mean duration of symptoms was 16 months. Mean size of calcific materials was 11.4 mm (range, 0-35 mm). Mean value of VAS and ASES scores were 6.5 (range, 1-10) and 47 (range, 8-95), respectively. Of 383 patients (76%), 59 (15%) had rotator cuff tear including 15 full-thickness tears on US or MRI. Patients with rotator cuff tears were significantly associated with older age, recurrent symptoms, menstrual disorders in females, and having undergone calcification removal surgery and rotator cuff repair (all p<0.05). CONCLUSIONS: This study reported demographic, radiographic, and clinical features of calcific tendinitis of the shoulder in Korean population, which were not different from those of Western population. Coexisting rotator cuff tear was found with 15% incidence in this large series, suggesting that further radiographic study to evaluate rotator cuff tear might be needed in some calcific tendinitis patients of older age and presenting with recurrent symptoms.

Clinical and Radiologic Outcomes of Combined Use of Biocomposite and PEEK Suture Anchors during Arthroscopic Rotator Cuff Repair: A Prospective Observational Study.

The aim of the current study was to evaluate the functional and radiologic outcomes of biocompatible non-absorbable PEEK (polyetheretherketone) and biocomposite (poly-L-lactic acid/poly(lactic-co-glycolic acid) 70% + ß-tricalcium phosphate) anchors, especially in terms of perianchor cyst formation during the first six months postoperatively. We prospectively analysed 29 patients who underwent arthroscopic rotator cuff repair between March and May 2019. Both PEEK and biocomposite suture anchors were used as lateral anchors in one body. Clinical outcomes were assessed using the shoulder range of motion (ROM), visual analogue scale (VAS) for pain and satisfactory score, American Shoulder and Elbow Surgeons (ASES) score, and Simple Shoulder Test (SST). All these were obtained in patients preoperatively at 3 and 6 months after surgery. The imaging evaluation included perianchor cyst formation, anchor absorption, repaired cuff integrity, and retear pattern. All functional outcomes significantly improved over time. The biocomposite anchor had a statistically significant tendency to form higher grades of fluid collection at 3 months after surgery. However, the perianchor cyst reduced by the sixth postoperative month. Six months postoperatively, the functional outcomes were improved after rotator cuff repair and similar degrees of perianchor cyst formation were observed, regardless of the suture anchor material used.

Free radical production in CA1 neurons induces MIP-1alpha expression, microglia recruitment, and delayed neuronal death after transient forebrain ischemia.

Several studies report microglial accumulation and activation in the CA1 area in response to transient forebrain ischemia (TFI). Here we examine the possibility that free radicals and chemokines mediate the transient activation of microglia. Free radicals are produced primarily in CA1 pyramidal neurons within 2 h of TFI. Administration of trolox, a vitamin E analog, led to the inhibition of free radical production and recruitment of microglia in the CA1 area. In addition, intrahippocampal injection of Fe2+ triggered free radical production in CA1 neurons, followed by the recruitment and activation of microglial cells into this area. TFI-induced expression of macrophage inflammatory protein-1alpha (MIP-1alpha) was increased in CA1 neurons before microglial recruitment, and blocked by trolox. Moreover, the MIP-1alpha level was upregulated in cultured hippocampal neurons exposed to Fe2+, suggesting an essential role of free radicals in TFI-induced expression of MIP-1alpha. Intracerebroventricular injection of vMIP-2 (viral macrophage inflammatory protein-2), a broad-spectrum peptide antagonist of chemokine receptors, attenuated microglial recruitment and delayed CA1 neuronal degeneration after TFI. Our data suggest that free radicals produced in CA1 neurons contribute to the recruitment and activation of microglia and neurodegeneration through MIP-1alpha expression.

Mortality and cause of death in distal radius fracture patients: A longitudinal follow-up study using a national sample cohort.

The various harmful impacts of distal radius fractures (DRFs) may cause adverse effects. Although previous studies have reported the adverse effects of DRFs on mortality, most studies were performed in adults of advanced age and paid little attention to confounding factors of mortality. Furthermore, most of these studies investigated the overall impact of DRFs on mortality without differentiating the specified causes of death.The purpose of the present study was to estimate the risk of mortality in DRF patients according to the cause of death.Data from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2002 to 2013 were collected. A total of 27,295 DRF participants who were 50 years or older were 1:4 matched with control participants for age, sex, income, and region of residence. The causes of death were grouped into 12 classifications.DRFs were not associated with increased overall mortality. The adjusted hazard ratio (HR) of mortality was 1.04 (95% confidence interval [CI] = 0.98-1.11, P = .237). The adjusted HR for mortality was not significantly different according to age. The odds ratio of overall mortality was 1.03 (95% CI = 0.97-1.11, P = .329).DRFs were not associated with a significant increase in mortality.

Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar beta amyloid peptide (1-42)-stimulated microglia.

Recent studies have reported that the cholinergic anti-inflammatory pathway regulates peripheral inflammatory responses via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and that acetylcholine and nicotine regulate the expression of proinflammatory mediators such as TNF-alpha and prostaglandin E2 in microglial cultures. In a previous study we showed that ATP released by beta-amyloid-stimulated microglia induced reactive oxygen species (ROS) production, in a process involving the P2X(7) receptor (P2X(7)R), in an autocrine fashion. These observations led us to investigate whether stimulation by nicotine could regulate fibrillar beta amyloid peptide (1-42) (fAbeta1-42)-induced ROS production by modulating ATP efflux-mediated Ca(2+) influx through P2X(7)R. Nicotine inhibited ROS generation in fAbeta(1-42)-stimulated microglial cells, and this inhibition was blocked by mecamylamine, a non-selective nAChR antagonist, and a-bungarotoxin, a selective alpha7 nAChR antagonist. Nicotine inhibited NADPH oxidase activation and completely blocked Ca(2+) influx in fAbeta(1-42)-stimulated microglia. Moreover, ATP release from fAbeta(1-42)-stimulated microglia was significantly suppressed by nicotine treatment. In contrast, nicotine did not inhibit 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP)-induced Ca(2+) influx, but inhibited ROS generation in BzATP-stimulated microglia, indicating an inhibitory effect of nicotine on a signaling process downstream of P2X(7)R. Taken together, these results suggest that the inhibitory effect of nicotine on ROS production in fAbeta1-42-stimulated microglia is mediated by indirect blockage of ATP release and by directly altering the signaling process downstream from P2X(7)R.

Cross talk between P2 purinergic receptors modulates extracellular ATP-mediated interleukin-10 production in rat microglial cells.

Previously we demonstrated that ATP released from LPS-activated microglia induced IL-10 expression in a process involving P2 receptors, in an autocrine fashion. Therefore, in the present study we sought to determine which subtype of P2 receptor was responsible for the modulation of IL-10 expression in ATP-stimulated microglia. We found that the patterns of IL-10 production were dose-dependent (1, 10, 100, 1,000 microM) and bell-shaped. The concentrations of ATP, ATP-gammaS, ADP, and ADP-betaS that showed maximal IL-10 release were 100, 10, 100, and 100 microM respectively. The rank order of agonist potency for IL-10 production was 2'-3'-O-(4-benzoyl)-benzoyl ATP (BzATP)=dATP>2-methylthio-ADP (2-meSADP). On the other hand, 2-methylthio-ATP (2-meSATP), alpha,beta-methylene ATP (alpha,beta-meATP), UTP, and UDP did not induce the release of IL-10 from microglia. Further, we obtained evidence of crosstalk between P2 receptors, in a situation where intracellular Ca(2+) release and/or cAMP-activated PKA were the main contributors to extracellular ATP-(or ADP)-mediated IL-10 expression, and IL-10 production was down-regulated by either MRS2179 (a P2Y(1) antagonist) or 5'-AMPS (a P2Y(11) antagonist), indicating that both the P2Y(1) and P2Y(11) receptors are major receptors involved in IL-10 expression. In addition, we found that inhibition of IL-10 production by high concentrations of ATP-gammaS (100 microM) was restored by TNP-ATP (an antagonist of the P2X(1), P2X(3), and P2X(4) receptors), and that IL-10 production by 2-meSADP was restored by 2meSAMP (a P2Y(12) receptor antagonist) or pertussis toxin (PTX; a Gi protein inhibitor), indicating that the P2X(1), P2X(3), P2X(4)receptor group, or the P2Y(12) receptor, negatively modulate the P2Y(11) receptor or the P2Y(1) receptor, respectively.

Can a Single Sagittal Magnetic Resonance Imaging Slice Represent Whole Fatty Infiltration in Chronic Rotator Cuff Tears at the Supraspinatus?

BACKGROUND: This study aimed to investigate whether fatty infiltration (FI) measured on a single sagittal magnetic resonance imaging (MRI) slice can represent FI of the whole supraspinatus muscle. METHODS: This study retrospectively reviewed the MRIs of 106 patients (age 50-79 years) divided into three rotator cuff tear-size groups: medium, large, and massive. Fat mass and muscle mass on all T1-weighted sagittal MRI scans (FA and MA) were measured. Of the total MRI scans, the Y-view was defined as the most lateral image of the junction of the scapular spine with the scapular body on the oblique sagittal T1-weighted image. Fat mass and muscle mass seen on this Y-view single slice were recorded as F1 and M1, respectively. Fat mass and muscle mass were also assessed on MRI scans lateral and medial to the Y-view. The means of fat mass and muscle mass on these three slices were recorded as F3 and M3, respectively. Average FI ratios (fat mass/muscle mass) of the three assessment methods (F1/M1, FA/MA, and F3/M3) were compared. Intraclass correlation coefficients (ICCs) were calculated for inter- and intraobserver reliability. RESULTS: ICCs showed higher reliability (> 0.8) for all measurements. F1/M1 values were not statistically different from FA/MA and F3/M3 values (p > 0.05), except in males with medium and large tears. F3/M3 and FA/MA were not statistically different. The difference between F1/M1 and FA/MA did not exceed 2%. CONCLUSIONS: A single sagittal MRI slice can represent the whole FI in chronic rotator cuff tears, except in some patient groups. We recommend measurement of FI using a single sagittal MRI slice, given the effort required for repeated measurements.