RESUMEN
Yak-Kong (YK) is a small black soybean widely cultivated in Korea. It is considered to have excellent health functionality, as it has been reported to have better antioxidant efficacy than conventional black or yellow soybeans. Since YK has been described as good for the muscle health of the elderly in old oriental medicine books, this study sought to investigate the effect of fermented YK with Bifidobacterium animalis subsp. lactis LDTM 8102 (FYK) on muscle atrophy. In C2C12 mouse myoblasts, FYK elevated the expression of MyoD, total MHC, phosphorylated AKT, and PGC1α. In addition, two kinds of in vivo studies were conducted using both an induced and normal aging mouse model. The behavioral test results showed that in the induced aging mouse model, FYK intake alleviated age-related muscle weakness and loss of exercise performance. In addition, FYK alleviated muscle mass decrease and improved the expression of biomarkers including total MHC, myf6, phosphorylated AKT, PGC1α, and Tfam, which are related to myoblast differentiation, muscle protein synthesis, and mitochondrial generation in the muscle. In the normal aging model, FYK consumption did not increase muscle mass, but did upregulate the expression levels of biomarkers related to myoblast differentiation, muscle hypertrophy, and muscle function. Furthermore, it mitigated age-related declines in skeletal muscle force production and functional limitation by enhancing exercise performance and grip strength. Taken together, the results suggest that FYK has the potential to be a new functional food material that can alleviate the loss of muscle mass and strength caused by aging and prevent sarcopenia.
Asunto(s)
Envejecimiento , Bifidobacterium animalis , Atrofia Muscular , Animales , Ratones , Atrofia Muscular/metabolismo , Masculino , Bifidobacterium animalis/fisiología , Fermentación , Modelos Animales de Enfermedad , República de Corea , Músculo Esquelético/metabolismo , Probióticos , Intestinos/microbiología , Alimentos de Soja , Humanos , Mioblastos/metabolismo , Glycine max/química , Ratones Endogámicos C57BLRESUMEN
The patient-specific bolus fabricated by a mold-and-cast method using a 3D printer (3DP) and silicon rubber has been adopted in clinical practices. Manufacturing a mold using 3DP, however, can cause time delays due to failures during the 3D printing process. Thereby, we investigated an alternative method of the mold fabrication using computer numerical control (CNC) machine tools. Treatment plans were conducted concerning a keloid scar formed on the ear and nose. The bolus structures were determined in a treatment planning system (TPS), and the molds were fabricated using the same structure file but with 3DP and CNC independently. Boluses were then manufactured using each mold with silicone rubbers. We compared the geometrical difference between the boluses and the planned structure using computed tomography (CT) images of the boluses. In addition, dosimetric differences between the two measurements using each bolus and the differences between the measured and calculated dose from TPS were evaluated using an anthropomorphic head phantom. Geometrically, the CT images of the boluses fabricated by the 3DP mold and the CNC mold showed differences compared to the planned structure within 2.6 mm of Hausdorff distance. The relative dose difference between the measurements using either bolus was within 2.3%. In conclusion, the bolus made by the CNC mold benefits from a stable fabricating process, retaining the performance of the bolus made by the 3DP mold.
Asunto(s)
Computadores , Impresión Tridimensional , Humanos , Fantasmas de Imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
Platycosides, major components of Platycodon grandiflorum (PG) extract, have been implicated in a wide range of biological effects. In particular, platycodin D (PD) is a well-known main bioactive compound of Platycosides. Despite the biological significance of PD, optimization of extract condition for PD from PG root has not been well investigated. Here, we established the optimum extraction condition as ethanol concentration of 0%, temperature of 50°C, and extraction time of 11 h to obtain PD-rich P. grandiflorum extract (PGE) by using response surface methodology (RSM) with Box-Behnken design (BBD). The 5.63 mg/g of PD was extracted from the PG root in optimum condition, and this result was close to the predicted PD content. To analyze the biological activity of PGE related to mucin production, we demonstrated the inhibitory effect of PGE on PMA-induced hyperexpression of MUC5AC as well as ERK activation, a signal mediator of MUC5AC expression. Moreover, we showed that PGE had expectorant activity in mice. These results indicated that PGE had sufficient functions as a potential mucoregulator and expectorant for treating diverse airway diseases. Additionally, we confirmed that PGE had antioxidant activity and inhibited LPS-induced proinflammatory cytokines, TNF-α, and IL-6. Taken together, PGE derived from novel optimizing conditions showed various biological effects, suggesting that PGE could be directly applied to the food industry as food material having therapeutic and preventive potential for human airway diseases.
RESUMEN
This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue.
Asunto(s)
Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Humanos , Reproducibilidad de los Resultados , Radiometría , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Lengua/diagnóstico por imagenRESUMEN
PURPOSE: The objective of this study was to fabricate an anthropomorphic multimodality pelvic phantom to evaluate a deep-learning-based synthetic computed tomography (CT) algorithm for magnetic resonance (MR)-only radiotherapy. METHODS: Polyurethane-based and silicone-based materials with various silicone oil concentrations were scanned using 0.35 T MR and CT scanner to determine the tissue surrogate. Five tissue surrogates were determined by comparing the organ intensity with patient CT and MR images. Patient-specific organ modeling for three-dimensional printing was performed by manually delineating the structures of interest. The phantom was finally fabricated by casting materials for each structure. For the quantitative evaluation, the mean and standard deviations were measured within the regions of interest on the MR, simulation CT (CTsim ), and synthetic CT (CTsyn ) images. Intensity-modulated radiation therapy plans were generated to assess the impact of different electron density assignments on plan quality using CTsim and CTsyn . The dose calculation accuracy was investigated in terms of gamma analysis and dose-volume histogram parameters. RESULTS: For the prostate site, the mean MR intensities for the patient and phantom were 78.1 ± 13.8 and 86.5 ± 19.3, respectively. The mean intensity of the synthetic image was 30.9 Hounsfield unit (HU), which was comparable to that of the real CT phantom image. The original and synthetic CT intensities of the fat tissue in the phantom were -105.8 ± 4.9 HU and -107.8 ± 7.8 HU, respectively. For the target volume, the difference in D95% was 0.32 Gy using CTsyn with respect to CTsim values. The V65Gy values for the bladder in the plans using CTsim and CTsyn were 0.31% and 0.15%, respectively. CONCLUSION: This work demonstrated that the anthropomorphic phantom was physiologically and geometrically similar to the patient organs and was employed to quantitatively evaluate the deep-learning-based synthetic CT algorithm.
Asunto(s)
Aprendizaje Profundo , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Pelvis/diagnóstico por imagen , Fantasmas de Imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is an imaging-based analytical technique that can characterize the surfaces of biomaterials. We used TOF-SIMS to identify important metabolites and oncogenic KRAS mutation expressed in human colorectal cancer (CRC). We obtained 540 TOF-SIMS spectra from 180 tissue samples by scanning cryo-sections and selected discriminatory molecules using the support vector machine (SVM) algorithm. Each TOF-SIMS spectrum contained nearly 860,000 ion profiles and hundreds of spectra were analyzed; therefore, reducing the dimensionality of the original data was necessary. We performed principal component analysis after preprocessing the spectral data, and the principal components (20) of each spectrum were used as the inputs of the SVM algorithm using the R package. The performance of the algorithm was evaluated using the receiver operating characteristic (ROC) area under the curve (AUC) (0.9297). Spectral peaks (m/z) corresponding to discriminatory molecules used to classify normal and tumor samples were selected according to p-value and were assigned to arginine, α-tocopherol, and fragments of glycerophosphocholine. Pathway analysis using these discriminatory molecules showed that they were involved in gastrointestinal disease and organismal abnormalities. In addition, spectra were classified according to the expression of KRAS somatic mutation, with 0.9921 AUC. Taken together, TOF-SIMS efficiently and simultaneously screened metabolite biomarkers and performed KRAS genotyping. In addition, a machine learning algorithm was provided as a diagnostic tool applied to spectral data acquired from clinical samples prepared as frozen tissue slides, which are commonly used in a variety of biomedical tests.
RESUMEN
The anti-skin inflammatory activities of rose petal extracts have been described in our previous study. Because skin inflammation is closely linked to skin aging, our study investigated the effects of Rosa gallica petals on skin aging-related activities such as skin whitening and anti-wrinkle properties. Each sample was prepared via extraction using different ethanol ratios with the objective of evaluationg optimal extraction conditions for industrial application. Aqueous 50% (v/v) EtOH extract of R. gallica petal significantly suppressed tyrosinase activity, melanin production, and solar UV-induced matrix metalloproteinase-1, a hall mark of wrinkle formation. In addition, the aqueous 50% (v/v) EtOH extract showed the highest antioxidative effect and had highest flavonoid contents, consistent with the reported anti-aging effects. Overall, our findings suggest that R. gallica petals extracts exhibit anti-aging effects. Furthermore, 50% EtOH extraction, in particular, was optimal for the highest anti-aging, and anti-oxidative effects as well as to obtain the highest flavonoid content.
RESUMEN
OBJECTIVE: To evaluate the efficacy and safety of CT-P10, a rituximab biosimilar after a single switch, during a multinational, randomized, double-blind Phase 3 trial involving patients with RA. METHODS: Patients received 48 weeks' treatment with CT-P10 or United States- or European Union-sourced reference rituximab (US-RTX and EU-RTX, respectively). Patients entering the extension period (weeks 48-72) remained on CT-P10 (CT-P10/CT-P10; n = 122) or US-RTX (US-RTX/US-RTX; n = 64), or switched to CT-P10 from US-RTX (US-RTX/CT-P10; n = 62) or EU-RTX (EU-RTX/CT-P10; n = 47) for an additional course. Efficacy endpoints included Disease Activity Score using 28 joints (DAS28), American College of Rheumatology (ACR) response rates, and quality of life-related parameters. Pharmacodynamics, immunogenicity and safety were also assessed. RESULTS: At week 72, similar improvements were observed by disease activity parameters including DAS28 and ACR response rate in the four extension period treatment groups. Quality of life improvements at week 72 vs baseline were similarly shown during the extension period in all groups. Newly developed anti-drug antibodies were detected in two patients following study drug infusion in the extension period. Similar pharmacodynamic and safety profiles were observed across groups. CONCLUSION: Long-term use of CT-P10 up to 72 weeks was effective and well tolerated. Furthermore, switching from reference rituximab to CT-P10 in RA was well tolerated and did not result in any clinically meaningful differences in terms of efficacy, pharmacodynamics, immunogenicity and safety. TRAIL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02149121.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Sustitución de Medicamentos , Rituximab/uso terapéutico , Adulto , Biosimilares Farmacéuticos , Método Doble Ciego , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Infliximab/uso terapéutico , Adulto , Anticuerpos Monoclonales/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Método Doble Ciego , Sustitución de Medicamentos , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Infliximab/efectos adversos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. METHODS: In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. RESULTS: Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (- 2.7 and - 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. CONCLUSION: CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. CLINICALTRIALS. GOV IDENTIFIER: NCT02149121.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/administración & dosificación , Rituximab/administración & dosificación , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Sedimentación Sanguínea/efectos de los fármacos , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Rituximab/efectos adversos , Adulto JovenRESUMEN
The subcortex is an important region in terms of swallowing function that passes fibers from the swallowing center to the cortex. However, studies on the relationship between the hemorrhage size and characteristics of dysphagia were lacking. In the present study, the relationship between subcortical hemorrhage size and characteristics of dysphagia was assessed in patients with subcortical hemorrhage. This study recruited retrospectively 49 subcortical hemorrhage patients with dysphagia. The hemorrhage size was measured and the clinical dysphagia scale (CDS) was used to evaluate the severity of dysphagia. The relationship between CDS score and hemorrhage size was analyzed. Subjects were divided into 2 groups according to average hemorrhage size of the subjects. The CDS scores of the 2 groups were compared and the relationship between each CDS item and hemorrhage size was analyzed. A significant positive correlation was observed between hemorrhage size and total CDS score. Also, a significant correlation was observed when patients over 70 years of age were excluded. The total CDS score in the large hemorrhage group was significantly higher than the CDS score in the small hemorrhage group. The CDS items including tracheostomy, lip sealing, tongue protrusion, laryngeal elevation, and reflex coughing were significantly correlated with hemorrhage size. In this study, the hemorrhage size in patients with subcortical hemorrhage correlated with the severity of dysphagia. In addition, the hemorrhage size was correlated with specific CDS items. These findings should be considered when treating subcortical hemorrhage patients with dysphagia in a clinical setting.
Asunto(s)
Hemorragia Cerebral/patología , Trastornos de Deglución/patología , Anciano , Corteza Cerebral/patología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/fisiopatología , Deglución/fisiología , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The aim of this study was to investigate the skin anti-inflammatory activity of rose petal extract (RPE) and the mechanisms underlying this phenomenon. Recently, flowers have been considered as dietary resources owing to their biological activities, such as inhibition of nephritis and hemorrhoids. The Rosa plant exerts various biological functions, including antioxidant and anti-microbiological activities. Herein, we confirmed the skin anti-inflammatory activity of RPE upon solar UV (sUV) exposure. RPE reduced sUV-induced COX-2 expression as well as expressions of several cytokines. Activation of MKK4-JNK, MEK-ERK, and MKK3-p38 signaling pathways, which are associated with cytokine production, was also attenuated by RPE treatment. We hypothesized these RPE-induced changes are because of its antioxidant activity, because RPE displayed drastic radical scavenging and oxygen radical absorbance capacity (ORAC). Furthermore, high anthocyanins, polyphenols, and flavonoids contents were found in RPE. Hence, these results indicated the skin anti-inflammatory activity of RPE is because of antioxidant activity.
RESUMEN
BACKGROUND: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. METHODS: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II-IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804. FINDINGS: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8%; 90% CI -6·43 to 10·20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. INTERPRETATION: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. FUNDING: Celltrion, Inc.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/farmacocinética , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Rituximab/uso terapéutico , Seguridad , Carga Tumoral , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/farmacología , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/farmacología , Biosimilares Farmacéuticos/uso terapéutico , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Linfoma Folicular/metabolismo , Masculino , Persona de Mediana Edad , Rituximab/efectos adversos , Rituximab/farmacocinética , Rituximab/farmacología , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
RATIONALE: Botulinum toxin A (BTX-A) injection is effective in treating focal dystonia. However, there are no prior reports regarding the treatment of progressive focal dystonia by a single BTX-A injection that affect a distant muscle. PATIENT CONCERNS: A 19-year-old male was referred to the rehabilitation clinic with a complaint of involuntary movement in his left big toe. The involuntary movement pattern was initially observed in the abduction direction only; however, it progressed to irregular mixed patterns in the flexion and abduction directions. DIAGNOSES: In needle electromyography, abnormal dystonic patterns were observed in the left abductor hallucis (AH), flexor hallucis longus, and flexor hallucis brevis muscles. INTERVENTIONS AND OUTCOMES: These symptoms resolved with a single BTX-A injection to the AH muscle. LESSONS: In this case, a single BTX-A injection to 1 muscle for treating progressive focal dystonia was effective on a distant noninjected muscle.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Trastornos Distónicos/tratamiento farmacológico , Fármacos Neuromusculares/administración & dosificación , Trastornos Distónicos/fisiopatología , Pie/fisiopatología , Hallux/fisiopatología , Humanos , Inyecciones Intramusculares , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
RATIONALE: Scapular winging is caused by neuromuscular dysfunction of shoulder stabilizer muscles. Clinically, a winged scapula can be easily diagnosed by typical physical findings. We report a case of atypical winged scapula caused by dorsal scapular neuropathy combined with suprascapular neuropathy, which has rarely been reported. PATIENT CONCERNS: A 25-year-old right-handed male was admitted to the clinic due to right arm weakness for 1 year. On physical examination, right winged scapula with medially rotated inferior angle was observed on flexion. DIAGNOSES: Under the diagnostic impression of a winged scapula due to long thoracic nerve injury based on physical examination, electrodiagnostic study was performed. However, the results showed right dorsal scapular neuropathy combined with suprascapular neuropathy. INTERVENTIONS: Neck and right shoulder MRI were also performed to rule out other causes of winged scapula, but these showed only a partial thickness tear of the rotator cuff tendon. The patient received rehabilitation. OUTCOMES: The symptoms have not improved. LESSONS: In this case, combined suprascapular neuropathy might contribute to scapular winging and can confuse the diagnosis of winged scapula based on physical findings. This is the first report that indicates suprascapular neuropathy as a contributing factor of scapular winging.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico/patología , Escápula/patología , Articulación del Hombro/patología , Adulto , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades del Sistema Nervioso Periférico/rehabilitación , Escápula/diagnóstico por imagen , Escápula/inervación , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/inervaciónRESUMEN
This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration-time curve (AUC) from time zero to last measurable concentration (AUC0-last), AUC from time zero to infinity (AUC0-∞), and maximum concentration (Cmax) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80-125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was -2.13 (0.175) for CT-P10 and -2.09 (0.176) for RTX. The 95% CI (-0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (-0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Rituximab/uso terapéutico , Adulto , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/farmacocinética , Antirreumáticos/efectos adversos , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapéutico , Área Bajo la Curva , Artritis Reumatoide/metabolismo , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/farmacocinética , Método Doble Ciego , Femenino , Humanos , Infecciones/inducido químicamente , Masculino , Persona de Mediana Edad , Rituximab/efectos adversos , Rituximab/farmacocinética , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
Kaempferia parviflora (Krachaidum (KD)) is a traditional herbal medicine and has properties that are beneficial for human health. In the current study, we sought to investigate the anti-inflammatory properties of KD extract (KPE). In mouse skin tissue, UV light representing solar wavelengths (sUV) increased COX-2 expression, while treatment with KPE reduced this effect. The anti-inflammatory activity of KPE was confirmed in in vitro models. MAPK signaling pathways were activated by sUV irradiation, and this was also repressed in the presence of KPE treatment. It is assumed that the anti-inflammatory activity of KPE is caused by the antioxidative effect. Furthermore, we confirmed the critical role of oxidative stress in sUV-induced COX-2 expression. We analyzed the polyphenol composition of KPE. Of the polyphenols identified, gallic acid, apigenin, and tangeretin were identified as the major polyphenols (at 9.31 ± 1.27, 2.37 ± 0.14, and 2.15 ± 0.19 µg/mg dry weight, resp.). Collectively, these findings show that in the presence of sUV irradiation, KD has anti-inflammatory properties and antioxidative effects in the skin.
Asunto(s)
Antioxidantes/uso terapéutico , Medicina de Hierbas/métodos , Zingiber officinale/química , Animales , Antioxidantes/farmacología , Humanos , RatonesRESUMEN
RATIONALE: Peripheral neuropathy is a rare complication of carbon monoxide intoxication. Peripheral neuropathy following carbon monoxide intoxication is known to completely recover within a few months. PATIENT CONCERNS: A 40-year-old man complained of motor weakness and hypoesthesia of the right lower extremity with swelling of his right thigh after carbon monoxide intoxication resulting from a suicide attempt. DIAGNOSES: Following nerve conduction and electromyographic studies, the patient was diagnosed with sciatic neuropathy with severe axonopathy. Clinical and laboratory findings led to a diagnosis of rhabdomyolysis. INTERVENTIONS: The patient was treated conservatively for rhabdomyolysis and underwent comprehensive rehabilitation for sciatic neuropathy during hospitalization. OUTCOMES: After discharge, he underwent serial follow-up tests with nerve conduction and electromyographic studies, which showed prolonged persistence of sciatic neuropathy; however, he showed significant improvement at his 26-month post-discharge follow-up. LESSON: Patients presenting with peripheral neuropathy secondary to carbon monoxide intoxication may show variable recovery periods; however, a favorable prognosis can be expected regardless of the concomitant occurrence of rhabdomyolysis and/or compartment syndrome.
Asunto(s)
Intoxicación por Monóxido de Carbono/complicaciones , Monóxido de Carbono/toxicidad , Rabdomiólisis/etiología , Neuropatía Ciática/etiología , Adulto , Síndromes Compartimentales/diagnóstico , Síndromes Compartimentales/etiología , Electromiografía/métodos , Humanos , Masculino , Conducción Nerviosa/fisiología , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Rabdomiólisis/diagnóstico , Rabdomiólisis/terapia , Neuropatía Ciática/fisiopatología , Neuropatía Ciática/rehabilitación , Intento de Suicidio/psicología , Resultado del TratamientoRESUMEN
Inflammation is a complex biological host reaction to tissue damage, infection and trauma. Extensive study of the inflammatory response has led to the identification of several protein kinases that are essential for signaling and could be potential therapeutic targets. The RSK family of kinases has multiple cellular functions. In our study, we found that RSK2 is a mediator for inflammation signaling and interacts with TRAF6. In vitro kinase assay results indicated that RSK2 strongly phosphorylates TRAF6 at serines 46, 47 and 48. Ectopic overexpression of TRAF6 or knocking down RSK2 expression confirmed that RSK2 is a positive regulator of TRAF6 K63 ubiquitination. TRAF6 is also required for RSK2 ubiquitination. TRAF6 bridges the TNF receptor superfamily and intracellular signaling for the induction of proinflammatory cytokines. We developed a colon inflammation model using RSK2 wild type (WT) and knockout (KO) mice. As expected, F4/80 and CD3 infiltration were significantly upregulated in WT mice compared to RSK2 KO mice. Furthermore, inflammation signaling, including Ikkα/ß, p38 and JNKs, was dramatically upregulated in WT mice. Colon tissue immunoprecipitation results further confirmed that TRAF6 K63 ubiquitination was lower in RSK2 KO mice. Overall, these results indicate that phosphorylation of TRAF6 (S46, 47, 48) by RSK2 is required for TRAF6 K63 ubiquitination and inflammation signaling.
Asunto(s)
Colitis/patología , Colon/patología , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Animales , Antígenos de Diferenciación/metabolismo , Complejo CD3/metabolismo , Línea Celular Tumoral , Colon/inmunología , Femenino , Células HEK293 , Humanos , Inflamación/patología , Péptidos y Proteínas de Señalización Intracelular , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Inhibidor NF-kappaB alfa/metabolismo , Fosforilación , Células RAW 264.7 , Ubiquitinación/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
PURPOSE: Access to trastuzumab, a valuable anti-cancer treatment, can be limited by cost. The primary aim of this study was to evaluate and compare the PK profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference trastuzumab (Herceptin®) in healthy subjects. Secondary study aims included comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in these subjects. METHODS: We performed a single-dose, randomised, double-blind, parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6 mg/kg, 90 min intravenous infusion) in 70 healthy adult males. Pharmacokinetics, safety and immunogenicity were evaluated up to 10 weeks post-dose. Primary endpoints were area under the serum concentration-time curve (AUC) from time 0 to infinity (AUCinf); AUC from time 0 to last quantifiable concentration (AUClast); and observed maximum serum concentration (Cmax). The pre-determined equivalence criterion was a 90% confidence interval of 80-125% for ratios of geometric least squares (LS) means. RESULTS: Equivalence of CT-P6 and reference trastuzumab was demonstrated. Ratios (CT-P6/reference trastuzumab) of geometric LS means (90% confidence interval) were: AUCinf 99.05 (93.00, 105.51); AUClast 99.30 (92.85, 106.20); Cmax 96.58 (90.93, 102.59). Safety profiles were similar; treatment-emergent adverse events occurred in ten subjects (28.6%) in the CT-P6 group and 11 (31.4%) in the reference trastuzumab group. No serious adverse events or deaths occurred. No subjects tested positive for anti-drug antibodies. CONCLUSIONS: These data add to the totality of evidence required to demonstrate biosimilarity. A phase III study of CT-P6-in which equivalent neoadjuvant efficacy to reference trastuzumab has been demonstrated-is ongoing.