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1.
Int J Mol Sci ; 23(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35163466

RESUMO

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and progression to chronic kidney disease (CKD). However, no effective therapeutic intervention has been established for ischemic AKI. Endothelial progenitor cells (EPCs) have major roles in the maintenance of vascular integrity and the repair of endothelial damage; they also serve as therapeutic agents in various kidney diseases. Thus, we examined whether EPCs have a renoprotective effect in an IRI mouse model. Mice were assigned to sham, EPC, IRI-only, and EPC-treated IRI groups. EPCs originating from human peripheral blood were cultured. The EPCs were administered 5 min before reperfusion, and all mice were killed 72 h after IRI. Blood urea nitrogen, serum creatinine, and tissue injury were significantly increased in IRI mice; EPCs significantly improved the manifestations of IRI. Apoptotic cell death and oxidative stress were significantly reduced in EPC-treated IRI mice. Administration of EPCs decreased the expression levels of NLRP3, cleaved caspase-1, p-NF-κB, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, RORγt, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-ß, α-SMA, Snail, and Twist) were significantly reduced in EPC-treated IRI mice. This study shows that inflammasome-mediated inflammation accompanied by immune modulation and fibrosis is a potential target of EPCs as a treatment for IRI-induced AKI and the prevention of progression to CKD.


Assuntos
Injúria Renal Aguda/prevenção & controle , Células Progenitoras Endoteliais/transplante , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/metabolismo , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Células Cultivadas , Creatinina/sangue , Modelos Animais de Doenças , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/imunologia , Células Progenitoras Endoteliais/metabolismo , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo
2.
Medicina (Kaunas) ; 58(1)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35056361

RESUMO

Hypokalemic periodic paralysis (HPP) is a neuromuscular disorder associated with muscular dysfunction caused by hypokalemia. There are various causes of HPPs and rarely, HPP appears to be relevant to tenofovir or glucocorticoid treatment. There have been several case reports of tenofovir-related nephrotoxicity or tenofovir-induced HPP. However, a case report of glucocorticoid-induced HPP in a patient using tenofovir temporarily has not been reported. Herein, we report a case of glucocorticoid-induced HPP with short-term use of tenofovir. A 28-year-old man visited the emergency room with decreased muscle power in all extremities (2/5 grade). In their past medical history, the patient was treated with tenofovir for two months for a hepatitis B virus infection. At the time of the visit, the drug had been discontinued for four months. The day before visiting the emergency room, betamethasone was administered at a local clinic for herpes on the lips. Laboratory tests showed hypokalemia, hypophosphatemia, and mild metabolic acidosis. However, urinalysis revealed no abnormal findings. Consequently, it can be postulated that this patient developed HPP by glucocorticoids after taking tenofovir temporarily. This is the first case report of glucocorticoid-induced HPP in a patient using tenofovir. Clinicians who prescribe tenofovir should be aware of HPP occurring when glucocorticoids are used.


Assuntos
Hipopotassemia , Paralisia Periódica Hipopotassêmica , Hipofosfatemia , Adulto , Glucocorticoides/efeitos adversos , Humanos , Hipopotassemia/induzido quimicamente , Paralisia Periódica Hipopotassêmica/induzido quimicamente , Paralisia Periódica Hipopotassêmica/diagnóstico , Paralisia Periódica Hipopotassêmica/tratamento farmacológico , Hipofosfatemia/induzido quimicamente , Masculino , Tenofovir/efeitos adversos
3.
Complement Ther Med ; 52: 102524, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32951763

RESUMO

INTRODUCTION: Momordica charantia (bitter melon) is widely used for its glucose-lowering effects. This study was conducted to assess the efficacy and safety of M. charantia as an adjuvant treatment in patients with type 2 diabetes. METHODS: We performed a randomized, placebo-controlled study. Blood glucose levels, lipid profile, and adverse events were investigated after 12 weeks of treatment. Ninety subjects were included in the final analysis for glucose lowering efficacy of bitter melon. RESULTS: There were no differences in age, sex, or glycated hemoglobin (HbA1c) levels between the bitter melon extract and placebo groups. After treatment with bitter melon extract for 12 weeks, the HbA1c levels of the bitter melon and placebo groups remained unchanged; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period. CONCLUSIONS: Our data showed that bitter melon has effects of glucose lowering in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Momordica charantia , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade
4.
Int J Mol Sci ; 21(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531940

RESUMO

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.


Assuntos
Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Glândulas Salivares/efeitos da radiação , Sialadenite/prevenção & controle , Ácido Tióctico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Aquaporina 5/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Ensaio de Imunoadsorção Enzimática , Feminino , Radioisótopos do Iodo/efeitos adversos , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/etiologia , Radioterapia/efeitos adversos , Radioterapia/métodos , Saliva/efeitos dos fármacos , Saliva/efeitos da radiação , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/fisiopatologia , Sialadenite/etiologia , Testes de Função Tireóidea
5.
Int J Mol Sci ; 20(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766286

RESUMO

Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient's daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation-induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.


Assuntos
Aparelho Lacrimal/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Ácido Tióctico/uso terapêutico , Fatores de Transcrição/metabolismo , Animais , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Aparelho Lacrimal/efeitos da radiação , Masculino , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
6.
Biomol Ther (Seoul) ; 27(5): 450-456, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30917626

RESUMO

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine's effect on anxiety. For the characterization of potential mechanism of taurine's anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine's anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

7.
J Bone Miner Metab ; 37(3): 563-572, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30238428

RESUMO

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.


Assuntos
Adesão à Medicação , Osteoporose Pós-Menopausa/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Conservadores da Densidade Óssea/uso terapêutico , Estudos Transversais , Difosfonatos/uso terapêutico , Feminino , Humanos , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , República da Coreia , Inquéritos e Questionários , Resultado do Tratamento
8.
Endocrine ; 64(2): 293-298, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30471053

RESUMO

PURPOSE: Long-term effects of iatrogenic hypothyroidism on renal function from thyroid hormone withdrawal during radioactive iodine therapy (RAIT) have not been studied, especially in subjects with mildly impaired renal function. We compared renal function in thyroid cancer subjects according to preparation method of either thyroid hormone withdrawal (THW) or injection of recombinant human thyrotropin (rhTSH). METHODS: This retrospective study enrolled 241 thyroidectomized patients (rhTSH group, n = 87 and THW group, n = 154). Changes in glomerular filtration rate (GFR) were measured prior to surgery, at the time of RAIT, and during a regular follow-up at least one year after RAIT. RESULTS: Baseline renal function was comparable between the rhTSH group and the THW group (91.4 mL/min/1.73 m2 vs. 92.4 mL/min/1.73 m2). At the time of RAIT, GFR was significantly decreased in the THW group (70.6 mL/min/1.73 m2, -23.6%), whereas renal function was preserved in the rhTSH group (85.4 mL/min/1.73 m2, -6.6%). In the THW group, renal function was fully recovered within 6 months after RAIT and was maintained up to 24 months, even in subjects with baseline GFR less than 90 mL/min/1.73 m2. CONCLUSIONS: THW for RAIT preparation induced considerable reduction in renal function, but this change was transient. In contrast, injection of rhTSH did not decrease renal function, making it a good option for RAIT preparation for subjects with renal dysfunction.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Hipotireoidismo/etiologia , Radioisótopos do Iodo/efeitos adversos , Rim/fisiopatologia , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Feminino , Humanos , Hipotireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/fisiopatologia , Tireoidectomia
9.
Biomed Res Int ; 2018: 8692078, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105256

RESUMO

The mechanisms by which hypoglycemia increases cardiovascular mortality remain unclear. The aim of the study is to investigate changes in serum electrolytes, norepinephrine concentrations, electrocardiography, and baroreflex sensitivity (BRS) and associations between corrected QT (QTc) intervals and the changes in serum electrolytes during combined pituitary stimulation test (CPST). We recruited the subjects who were admitted to the Gyeongsang National University Hospital to undergo CPST between September 2013 and December 2014. Participants were 12 patients suspected of having hypopituitarism. Among 12 patients, cardiac arrhythmia in two patients occurred during hypoglycemia. There were significant differences in serum levels of potassium (P < 0.001), sodium (P = 0.003), chloride (P = 0.002), and calcium (P = 0.017) at baseline, hypoglycemia, and 30 and 120 minutes after hypoglycemia. Also, there was a significant increase in heart rate (P = 0.004), corrected QT (QTc) interval (P = 0.008), QRS duration (P = 0.021), and BRS (P = 0.005) at hypoglycemia, compared to other time points during CPST. There was a positive association between QTc intervals and serum sodium levels (P < 0.001) in 10 patients who did not develop arrhythmia during CPST. This study showed that there were significant changes in serum levels of potassium, sodium, chloride, and calcium, as well as heart rate, QTc interval, QRSd, and BRS during CPST. It was revealed that QTc intervals had a significant association with concentrations of sodium.


Assuntos
Arritmias Cardíacas , Barorreflexo , Eletrocardiografia , Hipopituitarismo/fisiopatologia , Adulto , Eletrólitos/sangue , Feminino , Frequência Cardíaca , Humanos , Hipopituitarismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
PLoS One ; 13(8): e0202422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30125325

RESUMO

We examined the changes in thyroid hormone levels in patients with an acute clinical condition and compared these to levels in the healthy subjects. Serum total triiodothyronine (T3), thyroid stimulating hormone (TSH), and free thyroxine (fT4) measurements were recorded from 555 patients (mean age: 55.0 years, men: 65.9%) admitted to the emergency department (ED) 1-91 months (median: 34 months) after a regular health examination (HE). Serological data were analyzed; mean change in hormone levels was stratified by emergency classification system and quintiles of changes in inflammatory marker values, such as neutrophil lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (CRP). The mean decrease in T3 levels from HE and ED samples was 10.6 ng/dL (p< 0.001). Mean decrease in T3 levels was 21.6 ng/dL among patients classified as having an infection status and 11.0 ng/dL among patients classified as having an urgency status. A decrease 3.7 ng/dL among emergency patients was observed. TSH and fT4 levels did not change across all groups. When patients were stratified into quintiles according to changes in NLR values, mean decreases in T3 were 6.21, 8.14, 14.37, 12.76, and 21.98 ng/dL and showed significant linear reduction (p<0.001). For quintiles of changed CRP values, mean decreased T3 levels were 10.57, 3.05, 4.47, 7.68, and 28.07 ng/dL. TSH and fT4 were not associated with significant changes (p = 0.100, p = 0.561, respectively). In this study, thyroid function changes in individuals with an acute condition revealed that T3 significantly decreased, more markedly in infectious diseases compared to their healthy counterparts, and decline in T3 measurements correlated with inflammatory markers. TSH and fT4 levels remained stable. It is necessary to consider the severity of acute conditions when abnormal T3 levels are detected in subjects with emergent status.


Assuntos
Doenças da Glândula Tireoide/sangue , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Idoso , Serviço Hospitalar de Emergência , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
11.
Thyroid ; 28(7): 864-870, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29808777

RESUMO

BACKGROUND: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. METHODS: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. RESULTS: Thyroid cancer developed in 340 (0.26%) metformin users and 487 (0.38%) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 105 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. CONCLUSIONS: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , República da Coreia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
12.
Thyroid ; 28(2): 236-245, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29258382

RESUMO

BACKGROUND: The objective of this study was to determine the effect of a home-based exercise program on fatigue, anxiety, quality of life (QoL), and immune function of thyroid cancer patients taking thyroid hormone replacement after thyroidectomy. METHOD: This quasi-experimental study with a non-equivalent control group included 43 outpatients taking thyroid hormone replacement after thyroidectomy (22 in the experimental group and 21 in the control group). After education about the home-based exercise program, subjects in the experimental group underwent 12 weeks of aerobic, resistance, and flexibility exercise. A comparative analysis was conducted between the two groups. RESULTS: Patients in the experimental group were significantly less fatigued or anxious (p < 0.01). They reported significantly improved QoL (p < 0.05) compared to those in the control group. Natural killer cell activity was significantly higher in the exercise group compared to that in the control group (p < 0.05). CONCLUSION: A home-based exercise program is effective in reducing fatigue and anxiety, improving QoL, and increasing immune function in patients taking thyroid hormone replacement after thyroidectomy. Therefore, such a home-based exercise program can be used as an intervention for patients who are taking thyroid hormone replacement after thyroidectomy.


Assuntos
Ansiedade/terapia , Terapia por Exercício , Fadiga/terapia , Qualidade de Vida/psicologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto , Ansiedade/psicologia , Fadiga/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado , Inquéritos e Questionários , Neoplasias da Glândula Tireoide/psicologia
13.
J Altern Complement Med ; 24(3): 249-253, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28976210

RESUMO

BACKGROUND: Vigna nakashimae (VN) extract has been shown to have antidiabetic and antiobesity effects in various animal studies; however, to our knowledge, no data on such effects exist in humans. METHODS: We performed a randomized placebo-controlled study to investigate the antidiabetic effects of VN extract treatment for 12 weeks in humans. A total of 18 Korean patients with type 2 diabetes were enrolled in this study and were allocated randomly to either the VN extract group (1 g thrice daily) or control group (placebo tablets) for 12 weeks. We investigated blood glucose levels, body weight, lipid profiles, and adverse events after 12 weeks of treatment. Fifteen subjects were included in the final analysis. RESULTS: There was no difference in age, sex, fasting glucose levels, or lipid profiles between the VN extract and control groups at baseline. However, the baseline glycosylated hemoglobin (HbA1c) levels of the control group were lower than those of the VN extract group. After treatment with VN extract for 12 weeks, the body weight and lipid profile of the VN extract group remained unchanged; however, the HbA1C levels decreased by 0.36% ± 0.33% (p = 0.027). In contrast, the HbA1C levels of the control group did not change after 12 weeks (p = 0.228). During the 12-week treatment with VN extract, no serious adverse events were reported. CONCLUSION: Our data indicate that VN extract has implications for glucose lowering in type 2 diabetic patients.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Vigna/química , Adulto , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia
14.
Oncotarget ; 8(42): 72739-72747, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069822

RESUMO

PURPOSE: Radiotherapy is currently one of the main treatment modalities for head and neck cancer; however, it also results in severe toxicity to the normal tissue, to the detriment of patients. This study aimed to investigate whether alpha lipoic acid (ALA) could protect against radiation-induced oral mucositis in a rat model. RESULTS: On post-irradiation days 4 and 7, the epithelial layer on oral mucosa showed pronounced injury (shortening of the layer) and it is diminished by ALA pretreatment before radiation. Hif-1a expression was significantly induced in the radiation group on days 4, 7, and 28. GLUT1 expression was also induced by radiation at all time points, and the expression levels peaked on day 28. Phosphorylated p53 level was significantly higher in the radiation group on days 4 and 7, and Bax protein expression was significantly higher in the same group on day 4 than ALA-pretreated radiation group. TUNEL-positive staining was significantly lower in the ALA-pretreated radiation group. MATERIALS AND METHODS: Rats were assigned to one of the following four groups: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation, with the neck area including the oral mucosa evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were sacrificed 4, 7, 28, or 56 days after radiation. CONCLUSIONS: The results show that ALA can be used to ameliorate radiation-induced oral mucositis with head and neck cancer.

15.
J Clin Endocrinol Metab ; 102(2): 625-633, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27732329

RESUMO

Context: Small papillary thyroid cancer (PTC) generally has an excellent prognosis. However, long-term recurrence is not uncommon and sometimes leads to morbidity or mortality. Objective: To identify high-risk factors for long-term recurrence in patients with small PTC by stratifying their pathologic characteristics. Design, Setting, and Patients: We conducted a nationwide, retrospective, multicenter study of 3282 patients with PTC sized ≤2 cm from 9 high-volume hospitals in Korea. Main Outcome Measures: The maximally selected χ2 method was used to find the best cutoff points of tumor size, the number of metastatic lymph nodes (LNs), and the ratio of metastatic/examined LNs (LNR) to predict recurrence. Kaplan-Meier analysis and the Cox proportional hazards regression model were used to analyze recurrence and risk factors. Results: The optimal tumor size cutoff was 1.8 cm (10-year recurrence rates for tumors sized 0.1 to 1.7 cm and 1.8 to 2.0 cm: 7.7% vs 17.2%, respectively). Metastatic LNs ≤1 and ≥2 provided optimal estimates of recurrence (10-year recurrence rates: 4.0% vs 16.8%, respectively). The LNR of 0.19 was the optimal cutoff point for predicting the risk of recurrence (10-year recurrence rates for LNRs of 0 to 0.18 and 0.19 to 1: 2.7% vs 16.2%, respectively). LN metastasis, lobectomy, tumor size ≥1.8 cm, and bilateral tumors were independent risk factors for recurrence. Conclusions: Long-term recurrence was increased in patients who underwent lobectomy or with tumor sized ≥1.8 cm, 2 or more metastatic LNs, or bilateral tumors. For patients with these high-risk features, total thyroidectomy could be considered to avoid reoperation.


Assuntos
Carcinoma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Medição de Risco/métodos , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia/métodos , Adulto , Carcinoma/epidemiologia , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/estatística & dados numéricos
16.
Oncotarget ; 7(20): 29143-53, 2016 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-27072584

RESUMO

PURPOSE: Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. RESULTS: ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-ß1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. MATERIALS AND METHODS: Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. CONCLUSIONS: Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer.


Assuntos
Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Radioterapia/efeitos adversos , Glândulas Salivares/efeitos da radiação , Ácido Tióctico/farmacologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley
17.
Oncotarget ; 7(12): 15105-17, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-26943777

RESUMO

PURPOSE: Radiation therapy is a highly effective treatment for patients with solid tumors. However, it can cause damage and inflammation in normal tissues. Here, we investigated the effects of alpha-lipoic acid (ALA) as radioprotection agent for the small intestine in a mouse model. MATERIALS AND METHODS: Whole abdomen was evenly irradiated with total a dose of 15 Gy. Mice were treated with either ALA (100 mg/kg, intraperitoneal injection [i.p.]) or saline (equal volume, i.p.) the prior to radiation as 100 mg/kg/day for 3 days. Body weight, food intake, histopathology, and biochemical parameters were evaluated. RESULTS: Significant differences in body weight and food intake were observed between the radiation (RT) and ALA + RT groups. Moreover, the number of crypt cells was higher in the ALA + RT group. Inflammation was decreased and recovery time was shortened in the ALA + RT group compared with the RT group. The levels of inflammation-related factors (i.e., phosphorylated nuclear factor kappa B and matrix metalloproteinase-9) and mitogen-activated protein kinases were significantly decreased in the ALA + RT group compared with those in the RT group. CONCLUSIONS: ALA treatment prior to radiation decreases the severity and duration of radiation-induced enteritis by reducing inflammation, oxidative stress, and cell death.


Assuntos
Raios gama/efeitos adversos , Inflamação/tratamento farmacológico , Intestino Delgado/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/farmacologia , Ácido Tióctico/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Células Cultivadas , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/patologia , Intestino Delgado/lesões , Intestino Delgado/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/patologia
18.
Endocrinol Metab (Seoul) ; 31(1): 153-60, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26676337

RESUMO

BACKGROUND: The chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery. METHODS: This was a retrospective observational study that enrolled patients diagnosed with GC-induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 µg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels ≥18 µg/dL. RESULTS: Of the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05). CONCLUSION: In the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery.

19.
Intern Med ; 54(19): 2471-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26424306

RESUMO

Endocrine diseases are frequently accompanied by diabetes mellitus and treatment of an underlying endocrine disease often improves glucose control. The co-occurrence of acromegaly and Cushing's syndrome is extremely rare. We herein describe a patient who showed a dramatic improvement in glucose control following treatment for co-existing acromegaly and Cushing's syndrome. An adrenal mass was incidentally discovered during a routine evaluation of a 56-year-old woman who was subsequently diagnosed with acromegaly and a unilateral cortisol-producing adrenal adenoma. Her blood glucose was poorly controlled despite receiving high-dose insulin therapy. After undergoing adrenalectomy for Cushing's syndrome, her insulin dosage was decreased by almost 50%. The insulin treatment was discontinued following the treatment of acromegaly.


Assuntos
Acromegalia/diagnóstico , Adrenalectomia , Glicemia/metabolismo , Síndrome de Cushing/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Acromegalia/complicações , Acromegalia/cirurgia , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidrocortisona , Achados Incidentais , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Indução de Remissão
20.
PLoS One ; 10(8): e0136283, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26317525

RESUMO

Longitudinal studies on bone mass decline for healthy women are sparse. We performed a retrospective longitudinal study to evaluate the factor associated with bone mass changes at the lumbar spine in healthy Korean pre- and perimenopausal women over the age of 40. We examined the relation of blood tests including thyroid function tests at baseline and follow-up to the annual percentage changes in average BMD of L2-L4 (A%ΔLSBMD). Four hundred and forty-three subjects without diseases or medications pertaining to bone metabolism were analyzed. The mean A%ΔLSBMD in these subjects was -0.45%/year. Though a significant correlation was observed between the A%ΔLSBMD and age, serum thyroid-stimulating hormone (TSH) level, total cholesterol (TC) level, low-density lipoprotein cholesterol (LDL-C) level, and estimated glomerular filtration rate (eGFR) at baseline and follow-up, there was a weak correlation between A%ΔLSBMD and these variables. From multiple linear regression analyses, the percent body fat, age, serum TSH level, serum uric acid level, and the menopause at follow-up were showed to have a significant association with the A%ΔLSBMD. Unlike age, percent body fat, and menopause at follow-up, which had a negative association with the A%ΔLSBMD, serum TSH level and serum uric acid level, had a positive association with the A%ΔLSBMD. The results from our study showed that the notable risk factors of BMD loss at the lumbar spine in population of our study were advancing age, menopause, higher percent body fat, lower normal TSH, and lower serum uric acid levels.


Assuntos
Vértebras Lombares/patologia , Osteoporose/epidemiologia , Perimenopausa , Pré-Menopausa , Adulto , LDL-Colesterol/sangue , Feminino , Humanos , Vértebras Lombares/crescimento & desenvolvimento , Pessoa de Meia-Idade , Osteoporose/sangue , República da Coreia , Tireotropina/sangue , Ácido Úrico/sangue
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