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1.
bioRxiv ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38496399

RESUMO

Although estrogen affects the structure and function of the nervous system and brain and has a number of effects on cognition, its roles in the auditory and vestibular systems remain unclear. The actions of estrogen are mediated predominately through two classical nuclear estrogen receptors, estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). In the current study, we investigated the roles of ESR1 in normal auditory function and balance performance using 3-month-old wild-type (WT) and Esr1 knockout (KO) mice on a CBA/CaJ background, a normal-hearing strain. As expected, body weight of Esr1 KO females was lower than that of Esr1 KO males. Body weight of Esr1 KO females was higher than that of WT females, while there was no difference in body weight between WT and Esr1 KO males. Similarly, head diameter was higher in Esr1 KO vs. WT females. Contrary to our expectations, there were no differences in auditory brainstem response (ABR) thresholds, ABR waves I-V amplitudes and ABR waves I-V latencies at 8, 16, 32, and 48 kHz, distortion product otoacoustic emission (DPOAE) thresholds and amplitudes at 8, 16, and 32 kHz, and rotarod balance performance (latency to fall) between WT and Esr1 KO mice. Furthermore, there were no sex differences in ABRs, DPOAEs, and rotarod balance performance in Esr1 KO mice. Taken together, our findings show that Esr1 deficiency does not affect auditory function or balance performance in normal hearing mice, and suggest that loss of Esr1 is likely compensated by ESR2 or other estrogen receptors to maintain the structure and function of the auditory and vestibular systems under normal physiological conditions.

2.
Cancer Res Treat ; 55(4): 1250-1260, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37232070

RESUMO

PURPOSE: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. MATERIALS AND METHODS: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. RESULTS: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. CONCLUSION: Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.


Assuntos
Neoplasias Gástricas , Idoso , Humanos , Capecitabina , Neoplasias Gástricas/patologia , Oxaliplatina/efeitos adversos , Cisplatino , Recidiva Local de Neoplasia/tratamento farmacológico , Fluoruracila/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Chaperonas Moleculares/uso terapêutico , Proteínas Supressoras de Tumor
3.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36422527

RESUMO

Impatiens textori Miq. (ITM; family Balsaminaceae) is a traditional medicinal plant with many biological activities, which include anti-allergic, anti-inflammatory, and anti-pruritic properties. However, it remains to be determined whether ITM affects biological activities in the skin. Thus, we investigated the effects of ITM flower absolute (ITMFAb) extract on the biological activities of skin, especially those related to skin wound repair and whitening. ITMFAb was extracted with hexane, and its composition was determined through GC/MS. The biological activities of ITMFAb on HaCaT keratinocytes and B16BL6 melanoma cells were analyzed using a water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, a Boyden chamber, an ELISA, a sprouting assay, and by immunoblotting. These analyses were performed in a range of ITMFAb concentrations that did not inhibit the viability of the cells (HaCaT, ≤400 µg/mL; B16BL6, ≤200 µg/m). Forty components were identified in ITMFAb. ITMFAb stimulated proliferation, migration, sprout outgrowth, and type I and IV collagen synthesis and upregulated the activations of ERK1/2, JNK, p38 MAPK, and AKT in HaCaT cells. In addition, ITMFAb attenuated the serum-induced proliferation of B16BL6 cells. ITMFAb inhibited melanin synthesis, tyrosinase activity, and expressions of MITF and tyrosinase in α-MSH-exposed B16BL6 cells. These findings indicate that ITMFAb has beneficial effects on wound repairing and whitening-linked responses in the skin and suggest the potential use of ITMFAb as a natural material for the development of skin wound repair and whitening agents.

5.
Yonsei Med J ; 63(8): 759-766, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35914758

RESUMO

PURPOSE: Robotic head and neck surgery is widespread nowadays. However, in the reconstruction field, the use of robotic operations is not. This article aimed to examine methodologies for conventional head and neck reconstruction after robotic tumor surgery in an effort to obtain further options for future reconstruction manipulations. MATERIALS AND METHODS: A retrospective review of all patients who received head and neck robot surgery and conventional reconstructive surgery between October 2016 and September 2021. RESULTS: In total, 53 cases were performed. 67.9% of the tumors were greater than 4 cm. Regarding defect size, 47.2% of the lesions were greater than 8 cm. In terms of TNM stage, stage 3 disease was recorded in 26.4% and stage 4 in 52.8%. To make a deep and narrow field wider, we changed the patient's posture in pre-op field, additional dissection was done. We used radial forearm flap mostly (62.2%). CONCLUSION: Conventional head and neck reconstruction after robotic ENT cancer surgery is possible. One key step is to secure additional space in the deep and narrow space left after robotic surgery. For this, we opted for a radial forearm flap mostly. This can be performed as a bridgehead to perform robotic head and neck reconstruction.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias , Procedimentos de Cirurgia Plástica , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Robótica/métodos , Retalhos Cirúrgicos
6.
Molecules ; 26(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684753

RESUMO

Angelica polymorpha Maxim. (APM) is used in traditional medicine to treat chronic gastritis, rheumatic pain, and duodenal bulbar ulcers. However, it is not known whether APM has epidermis-associated biological activities. Here, we investigated the effects of APM flower absolute (APMFAb) on responses associated with skin wound healing and whitening using epidermal cells. APMFAb was obtained by solvent extraction and its composition was analyzed by GC/MS. Water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, Boyden chamber, sprouting, and enzyme-linked immunosorbent assays and immunoblotting were used to examine the effects of APMFAb on HaCaT keratinocytes and B16BL6 melanoma cells. APMFAb contained five compounds and induced keratinocyte migration, proliferation, and type IV collagen synthesis. APMFAb also induced the phosphorylations of ERK1/2, JNK, p38 mitogen-activated protein kinase, and AKT in keratinocytes. In addition, APMFAb decreased serum-induced B16BL6 cell proliferation and inhibited tyrosinase expression, melanin contents, and microphthalmia-associated transcription factor expression in α-melanocyte-stimulating hormone-stimulated B16BL6 cells. These findings demonstrate that APMFAb has beneficial effects on skin wound healing by promoting the proliferation, migration, and collagen synthesis of keratinocytes and on skin whitening by inhibiting melanin synthesis in melanoma cells. Therefore, we suggest that APMFAb has potential use as a wound healing and skin whitening agent.


Assuntos
Angelica/metabolismo , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flores/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Melaninas/biossíntese , Melaninas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo
7.
Chem Biodivers ; 18(10): e2100383, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34405949

RESUMO

Miscanthus sinensis var. purpurascens (MSP, flame grass) is found in Korea, Japan, and China, and its biological activities include anti-cancer, detoxifying, vasodilatory, antipyretic, and diuretic effects. However, no study has investigated the effects of MSP on skin-related biological activities. In this study, we explored the effects of the absolute extracted from the MSP flowers (MSPFAb) on skin wound healing- and whitening-related responses in keratinocytes or melanocytes. MSPFAb contained 6 components and induced the proliferation, migration, and syntheses of type I and IV collagens in keratinocytes. MSPFAb also increased the phosphorylations of serine/threonine-specific protein kinase, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase1/2 in keratinocytes. In addition, treatment with MSPFAb decreased serum-induced melanoma cell proliferation and inhibited tyrosinase activity and melanin contents in α-MSH-stimulated melanoma cells. Taken together, this study indicates MSPFAb may promote wound healing- and whitening-associated activities in dermal cells, and suggests that it has potential use as a wound healing and skin whitening agent.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flores/química , Extratos Vegetais/farmacologia , Poaceae/química , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células Tumorais Cultivadas
8.
J Korean Med Sci ; 36(12): e80, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33783145

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a serious clinical condition that impacts a patient's physical, psychological, and socio-economic status. The aim of this pilot study was to evaluate the effects of training with a newly developed powered wearable exoskeleton (Hyundai Medical Exoskeleton [H-MEX]) on functional mobility, physiological health, and quality of life in non-ambulatory SCI patients. METHODS: Participants received 60 minutes of walking training with a powered exoskeleton 3 times per week for 10 weeks (total 30 sessions). The 6-minute walking test (6MWT) and timed-up-and-go test (TUGT) were performed to assess ambulatory function. The physiological outcomes of interest after exoskeleton-assisted walking training were spasticity, pulmonary function, bone mineral density, colon transit time, and serum inflammatory markers. Effects of walking training on subjective outcomes were estimated by the Korean version of the Falls Efficacy Scale-International and the 36-Item Short-Form Health Survey version 2. RESULTS: Ten participants finished 30 sessions of training and could ambulate independently. No severe adverse events were reported during the study. After training, the mean distance walked in the 6MWT (49.13 m) was significantly enhanced compared with baseline (20.65 m). The results of the TUGT also indicated a statistically significant improvement in the times required to stand up, walk 3 m and sit down. Although not statistically significant, clinically meaningful changes in some secondary physiological outcomes and/or quality of life were reported in some participants. CONCLUSION: In conclusion, this study demonstrated that the newly developed wearable exoskeleton, H-MEX is safe and feasible for non-ambulatory SCI patients, and may have potential to improve quality of life of patients by assisting bipedal ambulation. These results suggest that the H-MEX can be considered a beneficial device for chronic non-ambulatory SCI patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04055610.


Assuntos
Exoesqueleto Energizado , Qualidade de Vida , Traumatismos da Medula Espinal/psicologia , Adulto , Densidade Óssea , Proteína C-Reativa/análise , Feminino , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular , Projetos Piloto , Estudos Prospectivos , Testes de Função Respiratória , Traumatismos da Medula Espinal/reabilitação , Estudos de Tempo e Movimento , Dispositivos Eletrônicos Vestíveis
9.
BMC Nephrol ; 22(1): 86, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691638

RESUMO

BACKGROUND: Thrombotic microangiopathy (TMA), a rare but serious complication of systemic lupus erythematosus (SLE), is associated with poor outcomes to conventional immunosuppressive therapy. Recently, eculizumab, a humanised monoclonal antibody that blocks the complement factor 5, has been known to effectively treat atypical haemolytic uremic syndrome (aHUS). Here, we report a case of aHUS co-existing with lupus nephritis that was successfully treated with eculizumab. CASE PRESENTATION: A 23-year-old man presented with abdominal pain and diarrhoea. Initial laboratory tests have shown thrombocytopaenia, microangiopathic haemolytic anaemia, and acute kidney injury. Immunologic tests were consistent with SLE. Kidney biopsy have revealed lupus nephritis class IV-G with TMA. Genetic analysis have shown complement C3 gene mutations, which hints the co-existence of lupus nephritis with aHUS, a form of complement-mediated TMA. Although initial treatment with haemodialysis, plasma exchange, and conventional immunosuppressive therapy (steroid and cyclophosphamide) did not appreciably improve kidney function and thrombocytopaenia, the patient was able to respond to eculizumab therapy. CONCLUSIONS: Due to the similar features of TMA and SLE, clinical suspicion of aHUS in patients with lupus nephritis is important for early diagnosis and prompt management. Timely administration of eculizumab should be considered as a treatment option for aHUS in lupus nephritis patients to yield optimal therapeutic outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Mutação , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/genética , Complemento C3/genética , Humanos , Nefrite Lúpica/complicações , Masculino , Adulto Jovem
10.
Anticancer Res ; 41(1): 391-402, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419836

RESUMO

BACKGROUND/AIM: Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS). PATIENTS AND METHODS: We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients. RESULTS: SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX. CONCLUSION: S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hepatopatia Veno-Oclusiva/etiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Adulto , Biomarcadores , Capecitabina/administração & dosagem , Gerenciamento Clínico , Combinação de Medicamentos , Feminino , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Incidência , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Estudos Retrospectivos , Baço/patologia , Esplenectomia , Tegafur/administração & dosagem , Resultado do Tratamento
11.
Clin Gastroenterol Hepatol ; 19(12): 2577-2586.e6, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32882425

RESUMO

BACKGROUND & AIMS: Long-term outcomes of constipation have not been evaluated fully. We investigated the incidence of Parkinson's disease, constipation-related surgery, and colorectal cancer (CRC) in patients with constipation and slow-transit constipation (STC), followed up for up to 20 years. METHODS: We collected data from 2165 patients (33.1% men; median patient age, 54 y; median symptom duration, 5.0 y) with a diagnosis of constipation (based on Rome II criteria) who underwent an anorectal function test and a colonic transit time study, from 2000 through 2010, at a tertiary university hospital in Seoul, South Korea. The presence of STC was determined from colonic transit time. We used the Kaplan-Meier method to analyze and compare cumulative probabilities of a new diagnosis of Parkinson's disease or CRC according to the presence of STC. The patients were followed up until the end of 2019. RESULTS: During a median follow-up period of 4.7 years (interquartile range, 0.7-8.3 y), 10 patients underwent constipation-related surgery. The cumulative probabilities of constipation-related surgery were 0.7% at 5 years and 0.8% at 10 years after a diagnosis of constipation. Twenty-nine patients (1.3%) developed Parkinson's disease; the cumulative probabilities were 0.4% at 1 year, 1.0% at 5 years, and 2.6% at 10 years after a diagnosis of constipation. At 10 years, 1.3% of patients with STC required constipation-related surgery and 3.5% of patients with STC developed Parkinson's disease; in contrast, none of the patients without STC required constipation-related surgery (P = .003), and 1.5% developed Parkinson's disease (P = .019). In multivariate analysis, patient age of 65 years or older at the diagnosis of constipation (hazard ratio, 4.834; 95% CI, 2.088-11.190) and the presence of STC (hazard ratio, 2.477; 95% CI, 1.046-5.866) were associated independently with the development of Parkinson's disease. Only 5 patients had a new diagnosis of CRC during the follow-up period. The risk of CRC did not differ significantly between patients with vs without STC (P = .575). CONCLUSIONS: In a long-term follow-up study of patients with constipation in Korea, most patients had no severe complications. However, patients older than age 65 years with a new diagnosis of STC might be considered for Parkinson's disease screening.


Assuntos
Neoplasias Colorretais , Doença de Parkinson , Idoso , Colo , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Feminino , Seguimentos , Trânsito Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia
12.
Lung Cancer ; 151: 8-15, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278671

RESUMO

OBJECTIVES: Accumulating evidence indicates anti-diabetic drug metformin has anti-cancer effect by controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients. MATERIALS AND METHODS: This randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every 3 weeks for six cycles. The patients received gemcitabine (1000 mg/m2) on days 1 and 8 and carboplatin (5 area under the curve) on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes. RESULTS: Metformin group showed no significant difference in the risk of progression and death compared to control group (progression: hazard ratio [HR] = 1.01 [95% confidence interval (CI) = 0.72 - 1.42], P = 0.935; death: HR = 0.95 [95% CI = 0.67-1.34], P = 0.757). Squamous cell carcinoma (SqCC) had significantly higher fluorodeoxyglucose (FDG) uptake on baseline PET image than non-SqCC NSCLC (P = 0.004). In the SqCC with high FDG uptake, the addition of metformin significantly decreased the risk of progression and death (progression: HR = 0.31 [95% CI = 0.12-0.78], P = 0.013; death: HR = 0.42 [95% CI = 0.18-0.94], P = 0.035). The HDL-cholesterol level was significantly increased after the treatment in metformin group compared to control group (P = 0.011). The metformin group showed no survival benefit in the patients with hyperinsulinemia or patients whose insulin level was decreased after treatment. CONCLUSIONS: Addition of metformin to chemotherapy provided no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metformina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/dietoterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Dieta , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/dietoterapia , Neoplasias Pulmonares/tratamento farmacológico , Metformina/uso terapêutico
13.
Hear Res ; 402: 108002, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32600853

RESUMO

Age-related hearing loss (AHL) is the most common form of hearing impairment. AHL is thought to be a multifactorial condition resulting from the interaction of numerous causes including aging, genetics, exposure to noise, and exposure to endogenous and exogenous toxins. Cells possess many detoxification enzymes capable of removing thousands of cytotoxic xenobiotics and endogenous toxins such as 4-hydroxynonenal (4-HNE), one of the most abundant cytotoxic end products of lipid peroxidation. The cellular detoxification system involves three phases of enzymatic detoxification. Of these, the glutathione transferase (GST) detoxification system converts a toxic compound into a less toxic form by conjugating the toxic compound to reduced glutathione by GST enzymes. In this review, we describe the current understanding of the cochlear detoxification system and examine the growing link between GST detoxification, oxidative lipid damage, ototoxicity, and cochlear aging with a particular focus on the alpha-class GSTs (GSTAs). We also describe how exposure to ototoxic drugs, exposure to noise, or aging results in increased 4-HNE levels, how 4-HNE damages various cell components under stress conditions, and how GSTAs detoxify 4-HNE in the auditory system.


Assuntos
Ototoxicidade , Envelhecimento , Aldeídos/toxicidade , Glutationa/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Peroxidação de Lipídeos , Lipídeos , Estresse Oxidativo
14.
Front Oncol ; 10: 577136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282731

RESUMO

BACKGROUND: Emerging radiation technologies are expected to provide a positive impact on the reduction in postoperative complications in patients receiving prosthetic breast reconstruction. This study aimed to determine whether hypofractionated radiation therapy(RT) with volumetric modulated arc therapy(VMAT) is superior to conventional RT in the setting of prosthetic reconstruction. METHODS: From retrospective data collections, postoperative complications were compared for all patients with mastectomy and staged prosthetic reconstruction without RT, with hypofractionation using 40 Gy in 15 fractions with VMAT (Hypo-VMAT) or conventional RT (50 Gy over 5 weeks). After harvesting subpectoral capsules from patients with informed consents, histologic analysis including immunohistochemistry and immunofluorescence for collagen type I, α-smooth muscle actin, CD34 and CD31 expression was performed. RESULTS: A total of 288 reconstructions without RT, 55 reconstructions with Hypo-VMAT, and 29 reconstructions with conventional RT were examined. During average follow-up period of 34.8 months, rates of overall complications were 6.3% in the no-radiation group, 18.2% in Hypo-VMAT group and 44.8% in conventional-RT group with significant differences (no-RT vs Hypo-VMAT: p=0.006; Hypo-VMAT vs conventional-RT: p=0.012). Levels of myofibroblasts and tissue fibrosis were lower in the Hypo-VMAT group than in conventional-RT group (p=0.016 and p=0.040, respectively), while those of progenitor cells and microvessel density were higher in the Hypo-VMAT group than in conventional-RT group (p<0.001 and p<0.001, respectively). CONCLUSION: We demonstrated that hypofractionated RT with VMAT served to reduce radiation-related morbidities in prosthetic reconstruction from a clinicopathologic perspective, compared to conventional RT. It may offer a practical strategy to mitigate radiation-related complications in clinical settings.

16.
J Neurol Sci ; 416: 117004, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622084

RESUMO

INTRODUCTION: Long-term efficacy and safety of subthalamic nucleus deep brain stimulation (STN DBS) in patients with young-onset Parkinson's disease (YOPD) and late-onset PD (LOPD) (i.e. motor symptom initial appearance at ages ≤40 and > 40 years, respectively) was compared to identify relationships between PD onset age and the efficacy of DBS. METHODS: Statistical analyses compared specific motor and non-motor features among 13 patients with YOPD and 11 with LOPD. Medication reduction patterns and dyskinesia severity scores at baseline and after 1, 3, 5, and 10 years of follow-up were also analyzed using a repeated measures ANOVA tests. Lastly, a correlation analysis identified relationships between the impact of DBS settings (volume of activated tissue) and levodopa equivalent daily dose (LED), dyskinesia severity scores, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and UPDRS part II (disability) scores. RESULTS: Ten years after DBS surgery, the reduction of LED from baseline (85.9 ± 592.6 mg versus 623.2 ± 464.9 mg; p = .023) and levodopa-induced dyskinesia (LID) scores (Unified Dyskinesia Rating Scale [UDysRS] parts III items 16-22; 1.6 ± 2.8 versus 5.5 ± 4.1; p = .013) were significantly lower in YOPD patients than LOPD patients. There were no significant differences between the two groups regarding UPDRS part III score improvement in response to levodopa, psychosis occurrence, or adverse effects. CONCLUSION: Ten years after STN DBS surgery, LOPD patients showed greater LED reduction, and YOPD patients showed greater LID improvement, although the general long-term outcomes were similar between YOPD and LOPD patients.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Adulto , Seguimentos , Humanos , Doença de Parkinson/terapia , Resultado do Tratamento
17.
J Korean Med Sci ; 35(1): e4, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31898433

RESUMO

BACKGROUND: The cognitive consequences and risk factors based long-term outcome of very-low-birth-weight (VLBW; < 1,500 g) infants in Korea has not been studied. The aim of this study was to determine the influence of perinatal and neonatal risk factors on the cognitive performance of VLBW children at 3 to 5 years of age. METHODS: We enrolled 88 VLBW infants without cystic periventricular leukomalacia for the assessment of their demographic data, cognitive performance, and development of cerebral palsy (CP) at 3 to 5 years of age. Cognitive performance was assessed using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence IV. Growth data were assessed with measurements of weight, height, and head circumference (HC) at the corrected ages of 6, 12, and 18 months, and 3 to 5 years of age. RESULTS: In the VLBW group, the full-scale intelligence quotient (FSIQ) was 96.1 ± 15.2 at the mean age of 4.5 years. The incidence rate of CP was 3.4%. Overall, 17% (15/88) of the VLBW children had a below-average FSIQ (< 85). We divided the VLBW children into the abnormal FSIQ group (< 85, n = 15) and the normal FSIQ group (≥ 85, n = 73). VLBW children with intrauterine growth retardation (IUGR) was associated with a below-average FSIQ at the mean age of 4.5 years (< 85, 8/15, 53.3% vs. ≥ 85, 5/73, 6.8%; P < 0.001). After controlling for associated clinical factors, IUGR in the VLBW children was found to be associated with an abnormal FSIQ at the mean age of 4.5 years (P = 0.025). The weight, height, and HC obtained for both groups showed that normal growth was maintained at the mean age of 4.5 years with no significant difference between abnormal and normal FSIQ groups. CONCLUSION: Fifteen of 88 (17%) of the VLBW children had a below-average FSIQ (< 85). VLBW with IUGR is associated with poor cognitive outcomes at the mean age of 4.5 years.


Assuntos
Cognição/fisiologia , Recém-Nascido de muito Baixo Peso , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/epidemiologia , Pré-Escolar , Feminino , Retardo do Crescimento Fetal/patologia , Idade Gestacional , Humanos , Testes de Inteligência , Modelos Lineares , Masculino , Razão de Chances , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Tradução
18.
Arch Plast Surg ; 46(6): 544-549, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31775207

RESUMO

BACKGROUND: As the indications for postmastectomy radiotherapy expand, innovative solutions are required to reduce operative complications and reconstructive failure after prosthetic breast reconstruction. In this study, we investigated the effectiveness of acellular dermal matrix (ADM) inlay grafts in preventing postoperative wound dehiscence of irradiated breasts in the context of prosthetic breast reconstruction. METHODS: A retrospective analysis was conducted of 45 patients who received two-stage prosthetic reconstruction and radiotherapy following mastectomy. An ADM graft was placed beneath the incisional site during the second-stage operation in 19 patients using marionette sutures, whereas the control group did not receive the ADM reinforcement. Patient demographics and complications such as wound dehiscence, capsular contracture, peri-prosthetic infection, cellulitis, and seroma were compared between the two groups. RESULTS: During an average follow-up period of 37.1 months, wound dehiscence occurred significantly less often in the ADM-reinforced closure group (0%) than in the non-ADM group (23.1%) (P=0.032). There was no significant difference between the two groups in relation to other complications, such as capsular contracture, postoperative infection, or seroma. CONCLUSIONS: The ADM inlay graft is a simple and easily reproducible technique for preventing incisional dehiscence in the setting of radiotherapy after prosthetic breast reconstruction. The ADM graft serves as a buttress to offload tension during healing and provides a mechanical barrier against pathogens. Application of this technique may serve to reduce complications in prosthetic breast reconstruction after radiotherapy.

19.
Nat Commun ; 10(1): 4150, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515474

RESUMO

Cisplatin is one of the most widely used chemotherapeutic drugs for the treatment of cancer. Unfortunately, one of its major side effects is permanent hearing loss. Here, we show that glutathione transferase α4 (GSTA4), a member of the Phase II detoxifying enzyme superfamily, mediates reduction of cisplatin ototoxicity by removing 4-hydroxynonenal (4-HNE) in the inner ears of female mice. Under cisplatin treatment, loss of Gsta4 results in more profound hearing loss in female mice compared to male mice. Cisplatin stimulates GSTA4 activity in the inner ear of female wild-type, but not male wild-type mice. In female Gsta4-/- mice, cisplatin treatment results in increased levels of 4-HNE in cochlear neurons compared to male Gsta4-/- mice. In CBA/CaJ mice, ovariectomy decreases mRNA expression of Gsta4, and the levels of GSTA4 protein in the inner ears. Thus, our findings suggest that GSTA4-dependent detoxification may play a role in estrogen-mediated neuroprotection.


Assuntos
Cisplatino/efeitos adversos , Glutationa Transferase/metabolismo , Ototoxicidade/enzimologia , Animais , Limiar Auditivo/efeitos dos fármacos , Capilares/patologia , Cóclea/enzimologia , Cóclea/patologia , Cóclea/fisiopatologia , Cruzamentos Genéticos , Dano ao DNA/genética , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/deficiência , Perda Auditiva/complicações , Perda Auditiva/enzimologia , Perda Auditiva/fisiopatologia , Masculino , Camundongos Endogâmicos CBA , Ototoxicidade/complicações , Ototoxicidade/patologia , Ototoxicidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/patologia
20.
Cancer Res Treat ; 51(3): 851-860, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31208165

RESUMO

PURPOSE: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. MATERIALS AND METHODS: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. RESULTS: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. CONCLUSION: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.


Assuntos
Cuidadores/psicologia , Terapias Complementares/psicologia , Neoplasias/terapia , Pacientes/psicologia , Idoso , Terapias Complementares/educação , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , República da Coreia , Inquéritos e Questionários
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