OI Treatment Research Articles

인라인스케이트 동호인 선수의 교정 인솔 착용과 발목 테이핑 처치가 동적 균형 능력 및 피로도에 미치는 영향

The purpose of this study was to examine the effects of orthodontic insole treatment and ankle Kinesio taping treatment on dynamic balance ability and fatigue of inline skaters. The subjects of the study were 20 male inline skaters (22.6±2.2 yrs) living in Seoul and Gyeonggi-do, classified into orthodontic insole treatment (OI treatment), ankle KT treatment (KT treatment), and general insole treatment (NI treatment) (cross-over design). Balance ability and physical fitness factors were measured according to the physical fitness measurement and evaluation manual of the Korea Institute of Sport Science (2007). Fatigue was measured by a wingate anaerobic test using a stationary bicycle (Ergomedic 894E, Sweden), and lactate was obtained by finger blood samples (10 μl) at rest, immediately after exercise, and at 5, 10, and 15 minutes after fatigue was induced. was analyzed. As a result of comparing dynamic balance ability, KT treatment (18.7±3.2 sec) and OI treatment (24.1±3.0 sec) were higher than NI treatment (12.9±3.1 sec), and OI treatment was higher than KT treatment (p＜.05). However, there was no difference in physical fitness factors and fatigue between the three treatments. In conclusion, it is considered that the wearing of corrective insoles for inline skaters can have a positive effect on dynamic balance ability within a short period of time as the effect of ankle Kinesio taping.

Itaconate alleviates β2-microglobulin-induced cognitive impairment by enhancing the hippocampal amino-β-carboxymuconate-semialdehyde-decarboxylase/picolinic acid pathway

β2-microglobulin (B2M) has been established to impair cognitive function. However, no treatment is currently available for B2M-induced cognitive dysfunction. Itaconate is a tricarboxylic acid (TCA) cycle intermediate that exerts neuroprotective effects in several neurological diseases. The amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD)/picolinic acid (PIC) pathway is a crucial neuroprotective branch in the kynurenine pathway (KP). The present study sought to investigate whether Itaconate attenuates B2M-induced cognitive impairment and examine the mediatory role of the hippocampal ACMSD/PIC pathway. We demonstrated that 4-Octyl Itaconate (OI, an itaconate derivative) significantly alleviated B2M-induced cognitive dysfunction and hippocampal neurogenesis impairment. OI treatment also increased the expression of ACMSD, elevated the concentration of PIC, and decreased the level of 3-HAA in the hippocampus of B2M-exposed rats. Furthermore, inhibition of ACMSD by TES-991 significantly abolished the protections of Itaconate against B2M-induced cognitive impairment and neurogenesis deficits. Exogenous PIC supplementation in hippocampus also improved cognitive performance and hippocampal neurogenesis in B2M-exposed rats. These findings demonstrated that Itaconate alleviates B2M-induced cognitive impairment by upregulation of the hippocampal ACMSD/PIC pathway. This is the first study to document Itaconate as a promising therapeutic agent to ameliorate cognitive impairment. Moreover, the mechanistic insights into the ACMSD/PIC pathway improve our understanding of it as a potential therapeutic target for neurological diseases beyond B2M-associated neurocognitive disorders.

4-octyl Itaconateinhibits lipopolysaccharide (LPS)-induced osteoarthritis via activating Nrf2 signalling pathway.

Small molecule drug intervention for chondrocytes is a valuable method for the treatment of osteoarthritis (OA). The 4‐octyl itaconate (OI) is a cellular derivative of itaconate with sound cell permeability and transformation rate. We attempted to confirm the protective role of OI in chondrocytes and its regulatory mechanism. We used lipopolysaccharide (LPS) to induce chondrocyte inflammation injury. After the OI treatment, the secretion and mRNA expression of Il‐6, Il‐10, Mcp‐1 and Tnf‐α were detected by ELISA and qPCR. The protective effect of OI on articular cartilage was further verified in surgical destabilization of the medial meniscus model of OA. Cell death and apoptosis were evaluated based on CCK8, LDH, Typan blue staining, Annexin V and TUNEL analyses. The small interfering RNAs were used to knockout the Nrf2 gene of chondrocytes to verify the OI‐mediated Nrf2 signalling pathway. The results revealed that OI protects cells from LPS‐induced inflammatory injury and attenuates cell death and apoptosis induced by LPS. Similar protective effects were also observed on articular cartilage in mice. The OI activated Nrf2 signalling pathway and promoted the stable expression and translocation of Nrf2 into the nucleus. When the Nrf2 signalling pathway was blocked, the protective effect of OI was significantly counteracted in chondrocytes and a mouse arthritis model. Both itaconate and its derivative (i.e., OI) showed important medical effects in the treatment of OA.

The utility of detecting ovulation to predict success in ovulation induction and intrauterine insemination cycles - a prospective observational study.

The success of ovulation induction-intrauterine insemination (OI-IUI) procedures may be limited by the absence of ovulation detection. The aim of this study was to evaluate the empirical use of ultrasonography and luteal phase progesterone (P4) as ovulation indicators and determine its effect on pregnancy outcome in OI-IUI cycles. This prospective observational study, which was performed in a university setting, included 107 women with unexplained infertility. Following OI, IUI was performed 36 hours after human chorionic gonadotropin (hCG). P4 was measured 72-96 hours after hCG. At the same time, the appearance of ovaries and signs indicative of ovulation, which are decreased follicle dimensions, irregularity of follicular walls, and the presence of free fluid in the Douglas pouch, were noted. In 58 patients (54.2%), ovulation was detected at the P4 level of > 10 ng/mL. Eighty-nine patients had ultrasound images suggestive of ovulation. However, only 50 of these were confirmed ovulation as indicated using P4. Implantation was observed in a total of 13 patients (12.1%). All patients were in the ovulation detected group with P4 > 10 ng/mL (AUC: 0.750; p = 0.004). P4 of > 21.5 ng/mL detected successful ovulation and was strongly associated with implantation with 77% sensitivity and 61% specificity (OR: 9.9; 95% CI: 2.4-41.2). Body mass index (BMI) > 23.9 kg/m2 was a reliable anovulation indicator as a secondary outcome (AUC: 0.696; p = 0.02). In 45.8% of the patients, ovulation did not occur even with OI treatment. The association of progesterone measurement and ovarian ultrasound scanning between 72 and 96 hours after hCG treatment can be used to detect ovulation. In doing so, we can find the optimal treatment for patients with infertility in their next cycle.

Itaconate prevents abdominal aortic aneurysm formation through inhibiting inflammation via activation of Nrf2.

AbsractBackgroundIdentifying effective drugs to suppress vascular inflammation is a promising strategy to delay the progression of abdominal aortic aneurysm (AAA). Itaconate has a vital role in regulating inflammatory activation in various inflammatory diseases. However, the role of itaconate in the progression of AAA is unknown. In this study, we explored the inhibitory effect of itaconate on AAA formation and its underlying mechanisms.MethodsQuantitative PCR, western blotting and immunohistochemistry were used to determine Irg1 and downstream Nrf2 expression in human and mouse AAA samples. Liquid chromatograph-mass spectrometry (LC-MS) analysis was performed to measure the abundance of itaconate. OI treatment and Irg1 knockdown were performed to study the role of OI in AAA formation. Nrf2 intervention in vivo was performed to detect the critical role of Nrf2 in the beneficial effect of OI on AAA.FindingsWe found that itaconate suppressed the formation of angiotensin II (Ang II)-induced AAA in apolipoprotein E-deficient (Apoe−/−) mice, while Irg1 deficiency exerted the opposite effect. Mechanistically, itaconate inhibited vascular inflammation by enabling Nrf2 to function as a transcriptional repressor of downstream inflammatory genes via alkylation of Keap1. Moreover, Nrf2 deficiency significantly aggravated inflammatory factor expression and promoted AAA formation. In addition, Keap1 overexpression significantly promoted Ang II-induced AAA formation, which was inhibited by itaconate.InterpretationItaconate inhibited AAA formation by suppressing vascular inflammation, and therapeutic approaches to increase itaconate are potentially beneficial for preventing AAA formation.FundingNational Natural Science Foundations of China and Guangzhou regenerative medicine and Health Laboratory of Guangdong.

The synergistic effect of NELL1 and adipose-derived stem cells on promoting bone formation in osteogenesis imperfecta treatment

BackgroundOsteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and deformity. Mesenchymal stem cells (MSCs) infusion can improve bone performance mainly due to their differentiation into osteoblasts in OI therapy. The osteoinductive activity of NELL1 have benefited various bone defect and osteoporotic models by promoting bone formation. The present study investigated the efficacy of combined use of NELL1 and adipose-derived mesenchymal stem cells (ADSCs) in OI treatment. MethodsLentiviral vector carrying mouse Nell1 gene was constructed and lentivirus were used to infect ADSCs. The osteogenic capacity of MC3T3-E1 and ADSCs stimulated by recombinant mouse NELL1 protein (rmNELL1) and Nell1 gene genetically modified ADSCs (lenti-Nell1-ADSCs) were estimated by real-time quantitative PCR. Thirty adult male OI type I mice with single Col1a1 gene knockout were randomly divided into five groups and received intravenously injected PBS, rmNELL1 (1.25 mg/Kg), ADSCs (2 × 105 cells per mice), rmNELL1 (1.25 mg/Kg) combined with ADSCs (2 × 105 cells per mice), or lenti-Nell1-ADSCs (2 × 105 cells per mice) respectively. Six wildtype (WT) mice served as positive control. Bone formation was examined after 4 weeks using micro-CT, histological and immunohistochemical methods. ResultsThree osteoblast related genes of MC3T3-E1 and ADSCs were significantly up-regulated by rmNELL1 in vitro. Lenti-Nell1-ADSCs showed greatly enhanced osteogenic differentiation capacity. The infused lenti-Nell1-ADSCs could migrate to femur and differentiate into ALPL-positive cells. Systemic administration of rmNELL1 combined with ADSCs or lenti-Nell1-ADSCs markedly improved the femoral microstructure and promoted bone formation through increasing the ALPL and osteocalcin (OCN) expression, much better than mice that received single rmNELL1 or ADSCs. And Nell1 gene engineered ADSCs achieved slightly better outcomes than that of combinative use of rmNELL1 and ADSCs. ConclusionsNELL1 and ADSCs exhibited synergistic effect on stimulating bone formation of OI mice, which might provide an alternative strategy in OI treatment. Compared with dose escalation or multiple administration of rmNELL1, lentivirus-mediated long term expression of NELL1 might be more feasible and convenient. However, further studies are needed to confirm the safety and optimize the therapeutic regime.

Itaconate Prevents Abdominal Aortic Aneurysm Formation Through Inhibiting Inflammation Via Activation of Nrf2

Background: Identifying effective drugs to suppress vascular inflammation is a promising strategy to delay the progression of abdominal aortic aneurysm (AAA). Itaconate has a vital role in regulating inflammatory activation in various inflammatory diseases. However, the role of itaconate in the progression of AAA is unknown. In this study, we explored the inhibitory effect of itaconate on AAA formation and its underlying mechanisms. Methods: Quantitative PCR, western blotting and immunohistochemistry were used to determine Irg1 and downstream Nrf2 expression in human and mouse AAA samples. Liquid chromatograph-mass spectrometry (LC-MS) analysis was performed to measure the abundance of itaconate. OI treatment and Irg1 knockdown were performed to study the role of OI in AAA formation. Nrf2 intervention in vivo were performed to detect the critical role of Nrf2 in the beneficial effect of OI on AAA. Findings: We found that itaconate suppressed the formation of angiotensin II (Ang II)-induced AAA in apolipoprotein E-deficient (Apoe-/-) mice, while Irg1 deficiency exerted the opposite effects. Mechanistically, itaconate inhibited vascular inflammation by enabling Nrf2 to function as a transcriptional repressor of downstream inflammatory genes via alkylation of Keap1. Moreover, Nrf2 deficiency significantly aggravated inflammatory factor expression and promoted AAA formation. In addition, Keap1 overexpression significantly promoted Ang II-induced AAA formation, which were inhibited by itaconate. Interpretation: Itaconate inhibited AAA formation by suppressing vascular inflammation, and therapeutic approaches to increase itaconate are potentially beneficial for preventing AAA formation. Funding: National Natural Science Foundations of China and Guangzhou regenerative medicine and Health Laboratory of Guangdong. Declaration of Interest: None. Ethical Approval: Human AAA samples were obtained from patients undergoing open surgical repair according to protocols approved by the Research Ethics Committees of Nanfang Hospital (ethical approval number: NFEC-2019-086). All animal protocols were approved by the Institutional Animal Care and Use Committee at Southern Medical University.

Effects of soil organic residue amendment on losses of dissolved organic carbon, P, Cu and Zn via surface runoff from arable soils

Dissolved organic carbon (DOC) constitutes the largest carbon pool in surface waters, with soil being its main source via surface and subsurface runoff. Amendment with organic residues can reduce soil erosion and surface runoff, but little is known how this affects the amount and composition of DOC losses via surface runoff and the associated transfer of nutrients and pollutants. In this study, artificial rainfall experiments were conducted on three pairs of soil runoff plots with contrasting organic matter management. A mixture of grass and wheat straw residues was incorporated into the topsoil of one plot in each pair (OI treatment) but not into the other (control). Artificial rainfall was applied onto both treatments at an intensity of 49.1 mm h−1, and surface runoff samples were collected at designated time steps for analysis of DOC, total dissolved phosphorus (TDP), copper (TDCu) and zinc (TDZn) concentrations, as well as for characterization of DOC by UV–vis absorbance (SUVA254 and E2:E3) and fluorescence spectroscopy (FI) indexes. The organic amendment reduced the loss rates of DOC, TDP, TDCu and TDZn by reducing surface runoff, although increasing the concentrations of DOC, TDP and TDCu. Regardless of the treatment, DOC, TDP and TDCu concentrations were always maximal at the onset of runoff and then continuously decreased after the initial flush. The observed relationships of TDP and TDCu concentrations with DOC indicate that the export of “dissolved” P and Cu primarily occurred in DOC-bound form, while the concentration of TDZn was not correlated with that of DOC. Surface runoff from the amended soils generally contained more hydrophilic and low molecular weight DOC (as indicated by low SUVA254 and high E2:E3 and FI values), particularly at high DOC concentrations. The ratio between TDCu and DOC concentration showed a positive relationship to DOC aromaticity (as indicated by SUVA254 values) in the OI treatment. The results indicate that organic amendment can reduce total rates of dissolved element losses with surface runoff, but attention should also be paid to the composition of lost DOC and the concentrations of DOC-associated solutes.

Access of Key Population to Available HIV and TB Services in Nepal: A Cross Section Study

Introduction: TB is considered one of the opportunistic infection among PLHIV. The increasing burden of HIV/TB co-infection among key population cause problem to maintain adherence to ART and DOTS services. The emergence of MDR-TB is one of the greatest challenge to control and management of both diseases. However, having knowledge and information of both diseases are important role to access the available HIV/TB services.
 Methods: A cross-sectional survey was conducted among key population who had HIV/TB co-infection in two-epidemic zone of Nepal. A pretested semi-structured questionnaire was used to collect data. ANOVA test was done to analyze the collected data by using SPSS version 20.0.
 Results: A total of 343 HIV/TB co-infected individuals were enrolled to the study. Most of participants were from ART and DOTS clients. Therefore, the study found that there was significance difference found between knowledge about TB (F=4.400, p= 0.005), causative agent of TB (F=3.160, p=0.025), risk of TB illness among PLHIV (F=8.491, p=0.001) and among key affected population. Moreover, there was significance difference found between access to OI treatment (F=5.113, p=0.002) and access to viral load (F=4.642, p=0.003) among key study population. In gender perspective, there was no significance difference to use and access to available HIV/TB services.
 Conclusion: The general knowledge on HIV/TB co-infection was significant association with key population. The knowledge on HIV/TB and access to NGOs’ help can significant effect to access the available HIV and TB services.

Erosion-induced losses of carbon, nitrogen, phosphorus and heavy metals from agricultural soils of contrasting organic matter management

Water erosion on agricultural land preferentially carries away fine particles. Due to the generally high specific density of sorption sites of these particles, their displacement can be associated with substantial particle-bound transfer also of nutrients and pollutants with low solubility. Organic matter amendments can reduce soil erosion, but to what extent they affect the erosion-induced element losses has not been studied much. Here, we carried out field rainfall experiments on three pairs of soil plots (1.5×0.75m) after incorporating a mixture of wheat straw and grass (2.12gC per kg soil) as organic amendment into the topsoil (0–5cm depth) of one plot in each pair (OI treatment). The other plot was prepared in the same way but without incorporation of the amendment (NI treatment). Artificial rainfall (49.1mmh−1) was simultaneously applied on each pair of plots for approximately 2h, and sediment samples were collected at designated time steps for the analyses of C, N, P, Cu, Zn and stable carbon isotope ratios. The organic amendment substantially reduced element losses, but to a lesser extent than soil loss, as the element concentrations were higher in the exported sediments in the OI than in the NI treatment. With and without organic amendment, the concentrations of the studied elements were consistently higher in the exported sediments than in the bulk soil. They were always maximal at the onset of discharge and then continuously decreased towards the values of the bulk soil. The δ13C values revealed that the eroded C was preferentially derived from the fresh organic residue added to the soil. Pairwise correlations between elements and sediment size indicate that the export of N, Cu and Zn was primarily associated with soil organic matter loss, whereas P export was more associated with mineral fractions.

Soil aggregate stability and size-selective sediment transport with surface runoff as affected by organic residue amendment

Aggregate breakdown influences the availability of soil particles for size-selective sediment transport with surface runoff during erosive rainfall events. Organic matter management is known to affect aggregate stability against breakdown, but little is known about how this translates into rainfall-induced aggregate fragmentation and sediment transport under field conditions. In this study, we performed field experiments in which artificial rainfall was applied after pre-wetting on three pairs of arable soil plots (1.5×0.75m) six weeks after incorporating a mixture of grass and wheat straw into the topsoil of one plot in each pair (OI treatment) but not on the other plot (NI treatment). Artificial rainfall was applied for approximately 2h on each pair at an intensity of 49.1mmh−1. In both treatments, discharge and sediment concentration in the discharge were correlated and followed a similar temporal pattern after the onset of surface runoff: After a sharp increase at the beginning both approached a steady state. But the onset of runoff was more delayed on the OI plots, and the discharge and sediment concentration were in average only roughly half as high on the OI as on the NI plots. With increasing discharge the fraction of coarse sediment increased. This relationship did not differ between the two treatments. Thus, due to the lower discharge, the fraction of fine particles in the exported sediment was larger in the runoff from the OI plots than from the NI plots. The later runoff onset and lower discharge rate was related to a higher initial aggregate stability on the OI plots. Terrestrial laser scanning proved to be a very valuable method to map changes in the micro-topography of the soil surfaces. It revealed a much less profound decrease in surface roughness on the OI than on the NI plots.

CABERGOLINE (CAB) TREATMENT FOR HYPERPROLACTINEMIC AMENORRHEAS IN ADOLESCENCE

Dopamine agonists represent the treatment of choice for hyperprolactinemic amenorrheas during adolescence. In order to evaluate a new long-acting drug CAB (l-[6 allylergolin-8-ß-il-carbonyl]-1-[3(diethylamino)propy1]3-ethylurea) we studied 5 hyperprolactinemic adolescents with a chronological age between 16 and 18 years (1 microadenoma, 2 residual hyperorolactinemias following pituitary aoenoma surgery and 2 idiopathic hyoerprolactinemias). Four of them received bromocriptine (BEC) during 24 weeks. Prolactin (PRL) was measured basally and after 4, 8, 12, 16, 20 and 24 weeks oi treatment. After a 4 week wash-out period, CAB was administered and PRL was measured basally and at monthly intervals for 48 weeks. The fifth catient only received CAB treatment for 48 weeks. BEC was administered at variable doses of 2.5 mg three or four times per day, and CAB was administered at a single weekly dose of 0.5 to 1mg. Serum PRL was measured by RIA and statistical evaluation was performed with Wiicoxon's test. Results are presented m the table (mean ± SEM). All patients resumed menstrual and ovulatory cycles. No tumor relapse was observed in the patients with residual hyperprolactinemias following pituitary surgery, whereas in the patient with microadenoma no tumor was visualized on CT at 48 weeks. Conclusions: 1) At 24 weeks there were no significant differences in the PRL values observed in patients treated with BEC or CAB. 2) The effect achieved with CAB persisted at 48 weeks. 3) CAB was effective in restoring gonadal function, mantaining asymptomatic patients who had undergone pituitary surgery and causing the tumor image to disappear. 4) Due to its long - acting properties, its ease of administration, and its low incidence of side-effects, CAB appears to be a useful treatment for hyperprolactinemia in adolescents.