Seizure Occurring 4 Days after Discontinuation of Long-term High-dose Zolpidem

Zolpidem is widely used for insomnia and is known to have relatively few side effects. There have been several reports of side effects, but only a few for withdrawal symptoms. A 41-year-old woman developed convulsions 4 days after discontinuing zolpidem. She was taking more than 10 times the standard dosage. After electroencephalography monitoring without antiseizure medications, she showed no more seizures. This case highlights the danger of zolpidem withdrawal and warns about the easy accessibility of zolpidem for individuals.

Diagnosis and pharmacological management of allergic conjunctivitis

Allergic conjunctivitis is an immune disease primarily attributed to a type 1 hypersensitivity reaction in the conjunctiva of the eye. Based on clinical findings and pathogenesis, allergic conjunctivitis is classified into the following subtypes: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis.Current Concepts: The recommended initial treatment for allergic conjunctivitis involves the use of dual-effect agents exerting both antihistamine and mast cell stabilizing effects. If symptoms persist despite the application of these agents, coexisting allergic rhinitis should be considered a possible contributing factor, as this condition can also lead to ocular symptoms. Concurrent treatment of allergic rhinitis is necessary. Although oral antihistamines effectively alleviate symptoms associated with allergic conjunctivitis, potential systemic side effects must be carefully considered, particularly in older individuals and children. Steroid eye drops should be used for limited durations to minimize side effects. Unlike seasonal and perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis involve both type 1 hypersensitivity reactions and type 4 hypersensitivity mediated by T cells. In cases where dual-effect agents or steroid eye drops fail to yield improvements, topical immunosuppressants such as cyclosporine A or tacrolimus can be effective.Discussion and Conclusion: The pharmacological treatment of allergic conjunctivitis involves the initial use of dual-effect agents, with concurrent treatment of allergic rhinitis if present. Importantly, atopic and vernal keratoconjunctivitis can potentially lead to permanent vision loss, necessitating the application of steroid eye drops or immunosuppressant eye drops.

Reference Respiratory Muscle Strength Values and a Prediction Equation Using Physical Functions for Pulmonary Rehabilitation in Korea

Background@#In Korea, tests for evaluating respiratory muscle strength are based on other countries’ clinical experience or standards, which can lead to subjective evaluations. When evaluating respiratory function based on the standards of other countries, several variables, such as the race and cultures of different countries, make it difficult to apply these standards. The purpose of this study was to propose objective respiratory muscle strength standards and predicted values for healthy Korean adults based on age, height, weight, and muscle strength, by measuring maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and peak cough flow (PCF). @*Methods@#This cross-sectional study analyzed MIP, MEP, and PCF in 360 people, each group comprising 30 adult men and women aged 20–70, diagnosed as healthy after undergoing medical check-ups at a general hospital. Hand grip strength (HGS) and the five times sitto-stand test (FTSST) results were also recorded. Correlations among respiratory muscle strength, participant demographics, and overall muscle strength were evaluated using Pearson’s correlation analysis. The predicted values of respiratory muscle strength were calculated using multiple regression analysis. @*Results@#Respiratory muscle strength differed from the values reported in studies from other countries. In the entire samples, both MIP and MEP had the highest correlations with peak HGS (r= 0.643, r = 0.693; P < 0.05), while PCF had the highest correlation with forced expiratory volume in 1 s (r = 0.753; P < 0.05). Age, body mass index, peak HGS, and FTSST results were independent variables affecting respiratory muscle strength. A predictive equation for respiratory muscle strength was developed using the multiple regression equation developed in this study. @*Conclusion@#Respiratory muscle strength index may differ by country. For more accurate diagnoses, standard values for each country are required. This study presents reference values for Korea, and a formula for estimation is proposed when no respiratory muscle strength measurement equipment is available.Trial Registration: Clinical Research Information Service Identifier: KCT0006778

Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists

Background@#To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care. @*Methods@#This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR. @*Results@#There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70). @*Conclusion@#Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients

Background@#The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. @*Methods@#We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. @*Results@#A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., 1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the 1.1 group, 17.2%, P1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9–1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD). @*Conclusion@#We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

TNM-Based Head-to-Head Comparison of Urachal Carcinoma and Urothelial Bladder Cancer: Stage-Matched Analysis of a Large Multicenter National Cohort / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. @*Materials and Methods@#Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. @*Results@#UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. @*Conclusion@#Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

Primary Intracranial Ewing Sarcoma With EWSR1-FLI1 GeneTranslocation Mimicking a Meningioma and a Multidisciplinary Therapeutic Approach: A Case Report and Systematic Review of Literatures

Ewing sarcoma and peripheral primitive neuroectodermal tumor (ES/pPNET) is an undifferentiated malignant tumor that is most prevalent in children and young adults and often radiologically mimics a meningioma. A 38-year-old female patient visited our hospital with complaints of right-sided tinnitus, right hemiparesis, and imbalance. She underwent preoperative imaging and was subsequently diagnosed as having a meningioma on the petrous ridge. After partial resection, EWSR1-FLI1 gene fusion was confirmed, and she was diagnosed with ES/pPNET. The tumor was successfully treated using a multidisciplinary approach of adjuvant chemo- and radiotherapy. This case is noteworthy because it is an extremely rare case of an intracranial ES/pPNET, and it is worth sharing our clinical experience that the tumor was successfully treated through a multidisciplinary therapeutic approach even though complete resection was not achieved.

MicroRNA-765 is upregulated in myelodysplastic syndromes and induces apoptosis via PLP2 inhibition in leukemia cells

Background@#Epigenetic studies, particularly research on microRNA (miRNA), have flourished. The abnormal expression of miRNA contributes to the development of hematologic malignancies.miR-765 has been reported to inhibit cell proliferation by downregulating proteolipid protein 2 (PLP2), which causes apoptosis. We investigated miR-765 dysregulation in myelodysplastic syndromes (MDS). @*Methods@#We compared the expression profiles of miR-765 in 65 patients with MDS and 11 controls.Cell proliferation and apoptosis assays were performed to determine the in vitro effects of miR-765 on leukemia cells transfected with the miR-765 mimic. Reverse transcription quantitative PCR (RT-qPCR) and western blotting were performed to examine the targets of miR-765. @*Results@#We found that miR-765 levels were upregulated 10.2-fold in patients with MDS compared to controls. In refractory cytopenia with multilineage dysplasia, the percentage of patients with elevated miR-765 levels was significantly higher than in other forms of MDS.Experiments with leukemia cells revealed that transfection with a miR-765 mimic inhibited cell proliferation and induced apoptosis. RT-qPCR and western blotting demonstrated that the target of miR-765 was PLP2. @*Conclusion@#These findings imply that upregulation of miR-765 induces apoptosis via downregulation of PLP2 and may have a role in MDS pathogenesis.

Imbalance in the spinal serotonergic pathway induces aggravation of mechanical allodynia and microglial activation in carrageenan inflammation

Background@#This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. @*Methods@#Male Sprague–Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation.Mechanical allodynia was measured using the von Frey test for 0–4 hours (early phase) and 24–28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. @*Results@#Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. @*Conclusions@#Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

The Extent of Silicone Oil Emulsification Revealed by Ultra-wide-field Fundus Photography and Optical Coherence Tomography

Purpose@#We assessed the extent of silicone oil (SO) emulsification using ultra-wide-field fundus photography (wFP) and the reflective ratios of swept-source optical coherence tomography (SS-OCT). @*Methods@#We retrospectively enrolled 51 eyes of 51 patients who underwent intravitreal SO tamponade with vitrectomy. Two weeks after SO tamponade and immediately before SO removal, ultra-wide-field fundus photography and SS-OCT were performed. Based on the numbers of emulsified droplets in the ultra-wide-field fundus photographs, SO emulsification was qualitatively graded from 0 to 4. Reflective ratios were calculated by dividing the OCT reflectivity of the optic cup by the OCT reflectivity of SO near the retinal surface. We analyzed the changes in the SO emulsification grade and the reflective ratio over time (RR2/RR1). @*Results@#The SO emulsification grade revealed by ultra-wide-field fundus photography was 2.12 ± 1.29, and the mean SS-OCT RR2/RR1 value was 1.14 ± 0.22. A longer duration of SO tamponade was associated with a higher emulsification grade on ultra-wide-field fundus photography and an increase in the RR2/RR1 value (both p < 0.01). We found a significant correlation between the SO emulsification grade on ultra-wide-field fundus photography and the SS-OCT RR2/RR1 (p = 0.028). @*Conclusions@#Ultra-wide-field fundus photography and SS-OCT can be used to determine objectively the extent of SO emulsification; this may indicate the appropriate SO removal time any complication.

Toggling Technique Allows Retrograde Early Release to Facilitate Neurovascular Bundle Sparing During Robot-Assisted Radical Prostatectomy: A Propensity ScoreMatching Study

Background@#This study aimed to present the surgical facilitation of neurovascular bundle (NVB) sparing using the toggling technique (30° lens down/up switching) and to evaluate erectile dysfunction (ED) recovery after robot-assisted radical prostatectomy (RARP). @*Methods@#We assessed 144 patients (group with toggling, n = 72; group without toggling, n = 72) who underwent RARP with bilateral NVB sparing using propensity score matching.Inclusion criteria were ≥ 1 year follow-up and preoperative potency as per the Sexual Health Inventory for Men (SHIM) questionnaire (≥ 17 points). Recovery of ED after RARP was defined as return to baseline sexual function or self-assessment regarding successful intercourse. The subjective surgeon’s nerve sparing (SNS) score and tunneling success rates were used to evaluate surgical facilitation. The recovery rate of ED between the groups was analyzed using Kaplan-Meier analysis. @*Results@#A better ED recovery trend was confirmed according to the SNS score (R 2 = 0.142, P = 0.004). In the analysis of NVB sparing ease, the toggling group showed higher SNS scores (on right/left side: P = 0.011 and < 0.001, respectively) and overall tunneling success rates (87% vs. 74%, P = 0.001) than the group without toggling. Overall, ED recovery rates were 82% (59/72) and 75% (54/72) in the groups with and without toggling, respectively, at the 1-year follow-up (P = 0.047), and the toggling group showed a faster ED recovery rate at 3 months (47% vs. 35%, P = 0.013). In a specific analysis of the potent cohort (< 60 years, bilateral full NVB spared, SHIM score ≥ 22), the ED recovery rate reached 87% (14/16) in the toggling group. @*Conclusion@#The retrograde early release with the toggling technique improves the facilitation of NVB sparing, leading to improved ED recovery.

Association between serum uric acid and relative hand grip strength in comparison with metabolic syndrome components

Objectives@#To investigate the association between serum uric acid (UA) and relative hand grip strength (HGS) in comparison with metabolic syndrome components. @*Methods@#We analyzed the data of 5247 Korean adults aged ≥ 20 years (2422 men and 2825 women) who participated in the KNHNES VII (2018). @*Results@#Among women, relative HGS was significantly lower in participants with hyperuricemia (1.65 ± 0.04) than in those without (1.95 ± 0.01) and was significantly decreased in the highest quartile (4Q: 1.77 ± 0.02) of serum UA compared with that in the lowest quartile (1Q: 1.98 ± 0.02). Among men, relative HGS was lower in participants with hyperuricemia (3.09 ± 0.04 vs. 3.16 ± 0.02) and decreased in 4Q (3.08 ± 0.03) of serum UA compared with that in 1Q (3.15 ± 0.03); however, these results were not statistically significant. In age- and multivariate-adjusted analyses in men, relative HGS was significantly lower in 4Q compared with that in 1Q in model 1 (adjusted for age), but there were no significant differences in model 2 (adjusted for age, BMI, and waist circumference) and model 3 (adjusted for age, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol). Meanwhile, in women, relative HGS was significantly decreased in 4Q compared with that in 1Q in all models. @*Conclusions@#A significant inverse correlation was observed between serum UA levels and relative HGS in women, and their significance was maintained even after adjusting for age and metabolic syndrome components.

Effect of Elastic Aids (Bands) on Functional Reach Test in Patients with Spinal Cord Injury: Pilot Study

Purpose@#This study aimed: to confirm the balance ability of patients with spinal cord injury in the sitting state through a functional reach test using an elastic aid; and to propose a balance improvement plan. @*Methods@#The study evaluated seven patients with spinal cord injury who could maintain a sitting posture through minimum assistance. A functional reach test was performed before and after wearing an elastic aid while sitting on a chair, and the effects before and after use of the elastic aid were compared and analyzed through a motion analyzer. @*Results@#In the functional reach test, the forward movement distance of the hand was 97.45 mm before wearing the elastic aid, but significantly increased to 131 mm after wearing the aid (p < 0.05). Corresponding forward movement distances for the shoulder were 81.26 mm and 113 mm (p < 0.05 for the increase). There was no statistically significant change in lateral functional arm extension. @*Conclusion@#It was confirmed, through a functional reach test, that trunk stability in patients with spinal cord injury increased with use of an elastic aid. In future, more efficient rehabilitation treatment programs will be possible if trunk stability in patients with spinal cord injury is improved by using elastic aids, and if various exercise treatments are also included in the rehabilitation programs.

Avascular Necrosis of the Capitate: MRI and Surgical Decision-Making of Two Case Reports

Avascular necrosis (AVN) is a rare disease occurring in the capitate of the wrist which is the third most common site of AVN among carpal bones. There are few reports on the MRI findings of AVN in the capitate bone. Besides, there is a paucity of reports showing the benefits of imaging for the choice of the treatment modality. We report two rare cases of capitate AVN requiring surgery.

Assessment of the Synergistic Effect of Seven Antimicrobial Combinations on Extensively DrugResistant Acinetobacter baumannii Strains / 대한임상미생물학회지

Background@#To solve the difficulty in determining the appropriate treatment regimen for patients infected with extensively drug-resistant Acinetobacter baumannii (XDRAB), it is necessary to develop various strategies to increase the therapeutic effect of antimicrobial agents. The purpose of this study was to select the treatment combination showing the greatest antimicrobial effect among seven candidate antimicrobial substances. @*Methods@#Seven strains of XDRAB were used in this study. The composition of the treatment consisted of colistin as the base and one of the seven antimicrobial substances, doripenem, minocycline, tigecycline, linezolid, fusidic acid, vancomycin, or alyteserin E4K peptide. The interaction between the drugs in each combination was evaluated by measuring the synergy rates using time-kill analysis. @*Results@#The synergy rates of the seven combinations tested in the time-kill assay in this study were as follows, in descending order from the combination with the highest synergy rate: colistin + minocycline (57.1%), colistin + alyteserin E4K (50.0%), colistin + tigecycline (42.9%), colistin + vancomycin (28.6%), colistin + doripenem (14.3%), colistin + fusidic acid (14.3%), and colistin + linzolid (0%). None of the combinations showed antagonism. The three combinations showing bactericidal activity and the rates of their bactericidal activity were colistin + alyteserin E4K combination (33.3%), colistin + minocycline (14.3%), and colistin + vancomycin (14.3%). @*Conclusion@#The colistin + minocycline and colistin + alyteserin E4K treatment combinations, which showed high synergy rates, can be considered as promising candidates for future in vivo experiments evaluating combination therapies.

Coronavirus disease 2019 pandemic-related change in children’s visits to the emergency department

Purpose@#This study was performed to investigate the coronavirus disease 2019 pandemic-related changes in visiting pattern of an emergency department (ED). @*Methods@#The author investigated all children younger than 19 years who visited the ED from 2018 through 2020 without exclusion criteria. Pandemic period was defined as 2020. Variables of interest were monthly and annual numbers of visits, age and age groups (< 1, 1-4, 5-9, 10-14, and 15-18 years), sex, visits for diseases, disposition, high acuity, and top 5 chief complaints per each age group. Timing of social distancing and influenza-related visits were additionally analyzed to speculate the impact of such variables on the visiting patterns. @*Results@#The annual visits were 11,435 (2018), 10,741 (2019), and 5,626 (2020), with a 47.6%-50.8% pandemic-related decrease. Trauma-related visits increased from 27.7%-28.4% to 36.5% (P < 0.001). In the children aged 9 years or younger, trauma as a chief complaint increased from 22.2%-29.6% to 36.2%-42.5% while fever decreased from 27.7%-47.3% to 16.7%-42.6%. In the pre-pandemic period, visits increased in February-March and October-December with a sharp increase in influenza-related visits in the latter 3 months. During the pandemic, a sharp decline in the visits was noted in January-February without the above-mentioned increasing patterns in neither total nor influenza-related visits. After the social distancing was implemented in the 13th week of 2020, the visits remained steady until a slight increase was noted after the school opening. @*Conclusion@#During the pandemic period, a decrease was noted in the numbers of visits to the ED, along with decreases in fever as a chief complaint in young children and influenza-related visits, and the mitigation of social distancing. These findings could be useful in preparing emergency medicine resources for ongoing and future pandemics.

Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4’-Dihydroxyflavone, U0126, and N-Acetyl Cysteine

Background and Objectives@#Flavonoids form the largest group of plant phenols and have various biological and pharma-cological activities. In this study, we investigated the effect of a flavonoid, 3, 4’-dihydroxyflavone (3, 4’-DHF) on osteogenic differentiation of equine adipose-derived stromal cells (eADSCs). @*Methods@#and Results: Treatment of 3, 4’-DHF led to increased osteogenic differentiation of eADSCs by increasing phosphorylation of ERK and modulating Reactive Oxygen Species (ROS) generation. Although PD98059, an ERK inhibitor, suppressed osteogenic differentiation, another ERK inhibitor, U0126, apparently increased osteogenic differentiation of the 3, 4’-DHF-treated eADSCs, which may indicate that the effect of U0126 on bone morphogenetic protein signaling is involved in the regulation of 3, 4’-DHF in osteogenic differentiation of eADSCs. We revealed that 3, 4’-DHF could induce osteogenic differentiation of eADSCs by suppressing ROS generation and co-treatment of 3, 4’-DHF, U0126, and/or N-acetyl cysteine (NAC) resulted in the additive enhancement of osteogenic differentiation of eADSCs. @*Conclusions@#Our results showed that co-treatment of 3, 4’-DHF, U0126, and/or NAC cumulatively regulated osteo-genesis in eADSCs, suggesting that 3, 4’-DHF, a flavonoid, can provide a novel approach to the treatment of osteoporosis and can provide potential therapeutic applications in therapeutics and regenerative medicine for human and companion animals.

Comparison of Clinical Outcomes between Arthroscopic Anterior Compartment Debridement with Posterior Compartment Mini-Open Debridement and Arthroscopic Both Compartments Debridement of the Primary Elbow Osteoarthritis / 대한정형외과학회잡지

Purpose@#This study analyzed the effectiveness of arthroscopic anterior compartment debridement with posterior mini-open debridement in patients with mild or moderate primary elbow osteoarthritis (OA). The clinical results of arthroscopic anterior compartment debridement with posterior mini-open debridement were compared with that of arthroscopic both compartments debridement. @*Materials and Methods@#Between January 2010 and December 2016, 46 patients diagnosed with elbow OA underwent arthroscopic anterior compartment debridement with posterior mini-open debridement or arthroscopic anterior and posterior compartments debridement arthroscopic surgery. Of these, 27 patients were finally included in this study. The data were collected retrospectively from the medical records. The subjects were divided into two groups according to the surgical procedure: group 1 (n=16) received arthroscopic anterior compartment debridement with posterior mini-open debridement surgery, and group 2 (n=11) received arthroscopic anterior and posterior compartments debridement surgery. The elbow flexion-extension range of motion (ROM), visual analog scale (VAS), Mayo Elbow Performance Score (MEPS) were analyzed for the clinical outcome before surgery and the last follow-up visit after surgery. @*Results@#The average follow-up period was 21 months (15–32 months). All clinical outcomes (ROM, VAS, and MEPS) were improved after surgery compared to those before surgery (p<0.05) in both groups. Group 1 showed further improvement in flexion (p=0.001) and total ROM (p=0.011) than group 2. On the other hand, there was no significant difference in extension, VAS, and MEPS between the two groups. @*Conclusion@#In patients with primary elbow OA, arthroscopic anterior compartment debridement with posterior compartment mini-open technique produced an excellent clinical outcome after surgery and was particularly helpful in increasing flexion and the total ROM.

Prostaglandin D2 contributes to cisplatin-induced neuropathic pain in rats via DP2 receptor in the spinal cord

Background@#Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomechanisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2 ) signaling in cisplatininduced neuropathic pain. @*Methods@#CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting. @*Results@#The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001). @*Conclusions@#The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.

Systemically administered neurotensin receptor agonist produces antinociception through activation of spinally projecting serotonergic neurons in the rostral ventromedial medulla

Background@#Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. @*Methods@#Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague–Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. @*Results@#Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. @*Conclusions@#These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.