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1.
Front Genet ; 15: 1342021, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463169

RESUMO

Gene expression profiling using RNA-sequencing (RNA-seq) and microarray technologies is widely used in cancer research to identify biomarkers for clinical endpoint prediction. We compared the performance of these two methods in predicting protein expression and clinical endpoints using The Cancer Genome Atlas (TCGA) datasets of lung cancer, colorectal cancer, renal cancer, breast cancer, endometrial cancer, and ovarian cancer. We calculated the correlation coefficients between gene expression measured by RNA-seq or microarray and protein expression measured by reverse phase protein array (RPPA). In addition, after selecting the top 103 survival-related genes, we compared the random forest survival prediction model performance across test platforms and cancer types. Both RNA-seq and microarray data were retrieved from TCGA dataset. Most genes showed similar correlation coefficients between RNA-seq and microarray, but 16 genes exhibited significant differences between the two methods. The BAX gene was recurrently found in colorectal cancer, renal cancer, and ovarian cancer, and the PIK3CA gene belonged to renal cancer and breast cancer. Furthermore, the survival prediction model using microarray was better than the RNA-seq model in colorectal cancer, renal cancer, and lung cancer, but the RNA-seq model was better in ovarian and endometrial cancer. Our results showed good correlation between mRNA levels and protein measured by RPPA. While RNA-seq and microarray performance were similar, some genes showed differences, and further clinical significance should be evaluated. Additionally, our survival prediction model results were controversial.

2.
Int J Mol Sci ; 24(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37894998

RESUMO

Korean ginseng (Panax ginseng) contains various ginsenosides as active ingredients, and they show diverse biological activities. Black ginseng is manufactured by repeated steaming and drying of white ginseng, which alters the polarity of ginsenosides and improves biological activities. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the ethanolic extract of black ginseng (BGE) in lipopolysaccharide (LPS)-induced BV2 microglial cells. Pre-treatment with BGE inhibited the overproduction of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 cells. In addition, BGE reduced the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) MAPK signaling pathways induced by LPS. These anti-neuroinflammatory effects were mediated through the negative regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) signaling pathway. Among the four ginsenosides contained in BGE, ginsenosides Rd and Rg3 inhibited the production of inflammatory mediators. Taken together, this investigation suggests that BGE represents potential anti-neuroinflammatory candidates for the prevention and treatment of neurodegenerative diseases.


Assuntos
Ginsenosídeos , Panax , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Fator 88 de Diferenciação Mieloide/metabolismo , Microglia/metabolismo , Receptor 4 Toll-Like/metabolismo , Ginsenosídeos/farmacologia , Ginsenosídeos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Panax/metabolismo , Transdução de Sinais , Doenças Neuroinflamatórias , Mediadores da Inflamação/metabolismo , Óxido Nítrico/metabolismo
3.
Biomed Pharmacother ; 153: 113385, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076523

RESUMO

Female menopause is a hormone deficiency phenomenon that causes hot flashes, vaginal dryness, depression, nervous tension, insomnia, obesity, and bone loss. There are various hormone replacement therapy (HRT)-based menopausal treatments, but they are accompanied by side effects such as endometrial cancer and hyperplasia. To confirm the menopausal improvement effect of Polygonatum sibiricum (PS), we prepared an ovariectomized animal model, administered 17ß-estradiol (E2) and PS, and analyzed various menopausal symptoms. PS restored vaginal epithelium thickness, by increasing the expression of estrogen receptors ERα (ESR1) and ERß (ESR2), and increased serotonin concentration by reducing serotonin receptor 1 A (5-HT1A) and glucocorticoid receptor (Gr) expression. In addition, PS suppressed obesity by increasing HDL-C and decreasing LDL-C levels and improved the osteoporosis induced by ovariectomy. In particular, by controlling Hand2, Fgf2, and Faf9 expression through PR, the antiproliferative signal was suppressed in uterine epithelium, thereby reducing the risk of side effects of the administration of E2 alone. These results demonstrate that PS alleviates menopausal symptoms without causing endometrial hyperplasia.


Assuntos
Polygonatum , Animais , Modelos Animais de Doenças , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Humanos , Menopausa , Camundongos , Obesidade/tratamento farmacológico , Ovariectomia
4.
J Clin Med ; 11(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35629073

RESUMO

The present study was designed to evaluate the relaxation effect of Rubus occidentalis (RO) and ellagic acid (EA) on rabbit penile corpus cavernosum smooth muscle (PCCSM). Rabbit PCCSM was treated with ROE or EA after preincubation with nitric oxide synthase (NOS), guanylate cyclase (GC), adenylyl cyclase (AC) or protein kinase A (PKA) blocker. Cyclic nucleotides in the perfusate were analyzed using radioimmunoassay (RIA). Subsequently, perfused PCCSMs were subjected to analysis to evaluate the expression level of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS). The interaction of ROE or EA with phosphodiesterase (PDE) 5 and PDE4 inhibitors, such as udenafil (UDE) and rolipram (ROL), were also evaluated. Both ROE and EA relaxed the PCCSM in a concentration-dependent manner. Coincubation of ROE or EA with NOS, GC, AC, or PKA blocker significantly decreased the ROE- and EA-induced relaxation. Pretreatment of ROE and EA significantly upregulated the cyclic guanosine monophosphate (cGMP), cyclic adenosine 3',5'-monophosphate (cAMP), and eNOS levels in the perfused PCCSM. Furthermore, the treatment of ROE and EA markedly increased the UDE- and ROL-induced relaxation of the PCCSM. In conclusion, ROE and EA induced PCCSM relaxation by activating the nitric oxide (NO)-cGMp and cAMp signaling pathways and may have a synergistic action to improve erectile function.

5.
Gynecol Oncol ; 164(3): 535-542, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34969535

RESUMO

OBJECTIVE: To ascertain whether cervical conization before radical hysterectomy (RH) has a protective effect on survival outcomes in early cervical cancer, taking into account the surgical approach. METHODS: From cervical cancer cohorts of two institutions, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH between July 2006 and June 2020. Patients were divided into conization group (n = 144) and control group (n = 434). We conducted three independent 1:1 propensity score matching processes for histology, lymphovascular space invasion, cervical tumor size, and surgical approach (all patients, those who underwent open surgery, and those who underwent minimally invasive surgery [MIS]). Survival outcomes were compared. RESULTS: Overall, the conization group had less cervical tumor size and received MIS more frequently (P = 0.010) and adjuvant treatment less often (P = 0.002) versus the controls. After matching, the conization group showed significantly better disease-free survival (DFS) versus control (3-year DFS rate, 94.2% vs. 86.3%; P = 0.012), but similar overall survival. Among the open RH matched patients (n = 96), no difference in DFS was observed between the conization and control groups (P = 0.984). In contrast, among the MIS RH matched patients (n = 192), the conization group showed significantly better DFS versus control (3-year DFS rate, 95.7% vs. 82.9%; P = 0.005). In multivariate analysis adjusting for cervical tumor size and adjuvant treatment, conization was identified as an independent favorable prognostic factor for DFS (adjusted HR, 0.318; 95% CI, 0.134-0.754; P = 0.009). CONCLUSIONS: Preoperative cervical conization might reduce the disease recurrence rate in early cervical cancer patients who undergo primary MIS RH.


Assuntos
Conização , Neoplasias do Colo do Útero , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
6.
BMC Complement Altern Med ; 19(1): 333, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771569

RESUMO

BACKGROUND: Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. METHODS: Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. RESULTS: Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. CONCLUSION: This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.


Assuntos
Iridoides/farmacologia , Quempferóis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Varicocele/metabolismo , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Testículo/química , Testículo/efeitos dos fármacos , Testículo/patologia , Varicocele/patologia
7.
BMC Complement Altern Med ; 19(1): 325, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752825

RESUMO

BACKGROUND: Osteoarthritis (OA) is an age-related joint disease with characteristics that involve the progressive degradation of articular cartilage and resulting chronic pain. Previously, we reported that Astragalus membranaceus and Lithospermum erythrorhizon showed significant anti-inflammatory and anti-osteoarthritis activities. The objective of this study was to examine the protective effects of ALM16, a new herbal mixture (7:3) of ethanol extracts of A. membranaceus and L. erythrorhizon, against OA in in vitro and in vivo models. METHODS: The levels of matrix metalloproteinase (MMP)-1, -3 and - 13 and glycosaminoglycan (GAG) in interleukin (IL)-1ß or ALM16 treated SW1353 cells were determined using an enzyme-linked immunosorbent and quantitative kit, respectively. In vivo, the anti-analgesic and anti-inflammatory activities of ALM16 were assessed via the acetic acid-induced writhing response and in a carrageenan-induced paw edema model in ICR mice, respectively. In addition, the chondroprotective effects of ALM16 were analyzed using a single-intra-articular injection of monosodium iodoacetate (MIA) in the right knee joint of Wister/ST rat. All samples were orally administered daily for 2 weeks starting 1 week after the MIA injection. The paw withdrawal threshold (PWT) in MIA-injected rats was measured by the von Frey test using the up-down method. Histopathological changes of the cartilage in OA rats were analyzed by hematoxylin and eosin (H&E) staining. RESULTS: ALM16 remarkably reduced the GAG degradation and MMP levels in IL-1ß treated SW1353 cells. ALM16 markedly decreased the thickness of the paw edema and writhing response in a dose-dependent manner in mice. In the MIA-induced OA rat model, ALM16 significantly reduced the PWT compared to the control group. In particular, from histological observations, ALM16 showed clear improvement of OA lesions, such as the loss of necrotic chondrocytes and cartilage erosion of more than 200 mg/kg b.w., comparable to or better than a positive drug control (JOINS™, 200 mg/kg) in the cartilage of MIA-OA rats. CONCLUSIONS: Our results demonstrate that ALM16 has a strong chondroprotective effect against the OA model in vitro and in vivo, likely attributed to its anti-inflammatory activity and inhibition of MMP production.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Cartilagem Articular/efeitos dos fármacos , Osteoartrite , Extratos Vegetais/farmacologia , Animais , Astragalus propinquus/química , Cartilagem Articular/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Glicosaminoglicanos/análise , Humanos , Ácido Iodoacético/efeitos adversos , Lithospermum/química , Masculino , Metaloproteinases da Matriz/análise , Medicina Tradicional do Leste Asiático , Camundongos Endogâmicos ICR , Osteoartrite/induzido quimicamente , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Substâncias Protetoras/farmacologia , Ratos
8.
Cancer Cell Int ; 19: 85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30992692

RESUMO

BACKGROUND: DA-9401 was prepared as a mixture of Chinese medicinal herb extracts from roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae). The present study was designed to investigate the possible protective role of DA-9401 in adriamycin (ADR)-induced testicular toxicity associated with oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis. METHODS: Fifty healthy 8-week-old male Sprague-Dawley rats were equally divided into five groups. The first CTR group was treated with normal saline 2 ml/day by gavage. The second was treated with DA-100 (DA-9401 100 mg/kg/day). The third (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and DA-9401 was given to the fourth ADR + DA-100 (100 mg/kg/day p.o) group and fifth ADR + DA-200 (200 mg/kg/day p.o) group. At the end of the 8-week treatment period, body weight, reproductive organ weights, fertility rate, pups per female were recorded, and serum were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathological changes, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), oxidative stress markers and expression levels of endoplasmic reticulum (ER) stress markers, apoptosis markers, tight junction protein markers, steroidogenic acute regulatory protein (StAR), cation channel of sperm (CatSper) and glycogen synthase kinase-3 (GSK-3) by western blot. RESULTS: DA-9401 administration to ADR-treated rats significantly decreased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, interleukin-6, TNF-α, MDA level, ROS/RNS level, ER stress response protein levels, tunnel positive cells, cleaved caspase-3, and Bax/Bcl2 ratio. Moreover, pretreatment with DA-9401 significantly increased body weight, reproductive organ weights, fertility rate, pups per female, Johnsen's score, spermatogenic cell density, sperm count and sperm motility, serum testosterone concentration, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), tight junction protein markers, star protein level, CatSper, and GSK-3 level. CONCLUSIONS: ADR treatment can markedly impair testicular function and induce testicular cell death presumably by causing significant changes in oxidative stress, ER stress, and mitochondrial pathway. DA-9401 exerts beneficial effects against oxidative stress, ER stress, and mitochondria-mediated cell death pathway in testis tissue by up-regulating expression levels of tight junction protein markers, steroidogenic acute regulatory protein, GSK-3 alpha, and cation channels of sperm.

9.
Can Urol Assoc J ; 13(11): E357-E360, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30817290

RESUMO

INTRODUCTION: We aimed to evaluate the effect of preoperative urethral dilatation during holmium laser enucleation of the prostate (HoLEP) on the prevention of urethral stricture. METHODS: A total of 72 patients without urethral stricture underwent HoLEP for benign prostatic hyperplasia (BPH). Recruited patients were randomly divided into two groups (groups A and B). Patients in group A (36 patients, experimental group) received preoperative urethral dilatation and patients in group B (36 patients, control group) did not. Each patient was evaluated at four weeks, 12 weeks, and 24 weeks after surgery. The effectiveness of preoperative urethral dilatation was evaluated based on the International Prostate Symptom Score (IPSS), peak urine flow rate (Qmax), voided volume, and post-void residual (PVR) volume. To diagnose urethral stricture, Qmax <10 mL/s, as assessed using uroflowmetry and findings of visualization through retrograde urethrography and urethroscopy, were used. RESULTS: Among 72 initial participants, 33 patients in group A and 31 patients in group B completed the experiment. Preoperative characteristics were well-balanced between groups. At each postoperative visit, there was no significant difference in voiding symptoms between groups. Two patients (6.06%) in group A and five patients (15.15%) in group B showed a Qmax <10 mL/s on uroflowmetry (p=0.013). On urethroscopy, no patient in group A (0%) and two patients in group B (6.45%) (p=0.021) showed urethral stricture after HoLEP. CONCLUSIONS: Preoperative urethral dilatation during HoLEP decreased the incidence of urethral stricture. This procedure could be useful to reduce the risk of urethral stricture after transurethral prostate surgery. One limitation of the current study is the single-centre design. Also, we sought to determine the efficacy of preoperative urethral dilatation for the prevention of urethral stricture after transurethral prostate surgery within a short time period, which could be another limitation of the study. Despite these limitations, to the best of our knowledge, the present study is the first reported prospective, randomized trial analyzing the safety and efficacy of preoperative urethral dilatation for the prevention of urethral stricture after transurethral prostate surgery.

10.
Drug Des Devel Ther ; 12: 1855-1863, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29970959

RESUMO

OBJECTIVE: We investigated the benefits of the BKCa agonist 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (LDD175) combined with tamsulosin and finasteride, in a benign prostatic hyperplasia (BPH) rat model. MATERIALS AND METHODS: Castration was performed by bilateral orchiectomy under ketamine anesthesia. A rat model of BPH was established by daily intramuscular administration of testosterone propionate plus 17ß-estradiol for 8 weeks. Model rats were administered combinations of 20 mg/kg LDD175, 0.01 mg/kg tamsulosin and 1 mg/kg finasteride once daily by oral gavage for 4 weeks from week 6 to 9 post-surgery. Intraurethral pressure induced by electrostimulation of the hypogastric nerve was measured at the end of administration. Body and genitourinary organ weights were recorded, serums were assayed for hormone concentrations, and tissues were subjected to histopathology, and analyses of α1-adrenoceptor mRNA and protein expression levels after treatment. RESULTS: Combined LDD175, tamsulosin, and finasteride significantly decreased prostatic index, serum hormone levels, epithelial thickness, and prostate expression of α1-adrenoceptors in BPH model rats. The 3-drug combination was more effective than any other combination or LDD175 alone. CONCLUSION: These results suggest that LDD175 addition to tamsulosin and finasteride may be beneficial for the treatment of BPH patients who do not respond to tamsulosin plus finasteride.


Assuntos
Benzofuranos/administração & dosagem , Finasterida/administração & dosagem , Indóis/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Sulfonamidas/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Hiperplasia Prostática/sangue , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/análise , Receptores Adrenérgicos alfa 1/genética , Tansulosina , Testosterona/sangue
11.
Molecules ; 23(2)2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-29382138

RESUMO

A new ginsenoside, named ginsenoside Rh23 (1), and 20-O-ß-d-glucopyranosyl-3ß,6α,12ß,20ß,25-pentahydroxydammar-23-ene (2) were isolated from the leaves of hydroponic Panax ginseng. Compounds were isolated by various column chromatography and their structures were determined based on spectroscopic methods, including high resolution quadrupole/time of flight mass spectrometry (HR-QTOF/MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy. To determine anti-melanogenic activity, the change in the melanin content in melan-a cells treated with identified compounds was tested. Additionally, we investigated the melanin inhibitory effects of ginsenoside Rh23 on pigmentation in a zebrafish in vivo model. Compound 1 inhibited potent melanogenesis in melan-a cells with 37.0% melanogenesis inhibition at 80 µM and also presented inhibition on the body pigmentation in zebrafish model. Although compound 2 showed slightly lower inhibitory activity than compound 1, it also showed significantly decreased melanogenesis in melan-a cell and in zebrafish model. These results indicated that compounds isolated from hydroponic P. ginseng may be used as new skin whitening compound through the in vitro and in vivo systems. Furthermore, this study demonstrated the utility of MS-based compound 1 for the quantitative analysis. Ginsenoside Rh23 (1) was found at a level of 0.31 mg/g in leaves of hydroponic P. ginseng.


Assuntos
Antineoplásicos Fitogênicos , Ginsenosídeos , Melanoma/tratamento farmacológico , Panax/química , Folhas de Planta/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Ginsenosídeos/farmacologia , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Peixe-Zebra
12.
Drug Des Devel Ther ; 10: 3959-3968, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28003740

RESUMO

Cisplatin (CIS) is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg) administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell, hematocrit, hemoglobin, and endoplasmic reticulum stress protein levels all increased. Though CIS effectively treats cancer, at an increased dose it is toxic and life-threatening to the genitourinary system and other parts of the body.


Assuntos
Cisplatino/administração & dosagem , Cisplatino/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/lesões , Animais , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/sangue , Contagem de Espermatozoides , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/metabolismo
13.
Int J Urol ; 23(3): 259-65, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26646436

RESUMO

OBJECTIVES: To investigate the effect of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid, a new benzofuroindole derivative, on the intraurethral pressure in a rat model of benign prostatic hyperplasia. METHODS: Benign prostatic hyperplasia was induced by testosterone and 17ß-estradiol, which were administered intramuscularly once a day for 12 weeks. The effects of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid and tamsulosin on the intraurethral pressure induced by the electrostimulation of hypogastric nerves after a single intravenous injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (10 mg/kg) or tamsulosin (10 µg/kg) were evaluated in a benign prostatic hyperplasia model. The electrostimulation-induced intraurethral pressure was measured just before and after the injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid. Bodyweight and genitourinary organ weights were recorded, and serums and tissues were subjected to hormone assays and histopathology. In addition, the expression of α1-adrenoceptors in the prostate was measured by western blotting. RESULTS: The benign prostatic hyperplasia groups showed increased prostatic index, increased concentrations of testosterone, free testosterone and estradiol in serum, and increased epithelial thickness of the prostate. An injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin significantly inhibited the elevation of electrostimulation-induced intraurethral pressure. In addition, 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid did not cause a significant change in the blood pressure compared with tamsulosin. While the benign prostatic hyperplasia group showed increased the expression of α1-adrenoceptors, the 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin injection into a rat model of benign prostatic hyperplasia decreased the expression of α1-adrenoceptors. CONCLUSIONS: These findings show that 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid might be beneficial for lowering the intraurethral pressure associated with benign prostatic hyperplasia, and it could represent a therapeutic option for benign prostatic hyperplasia patients.


Assuntos
Benzofuranos/farmacologia , Indóis/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Sulfonamidas/farmacologia , Uretra/efeitos dos fármacos , Animais , Benzofuranos/administração & dosagem , Modelos Animais de Doenças , Estimulação Elétrica , Estradiol/sangue , Estradiol/farmacologia , Humanos , Indóis/administração & dosagem , Masculino , Pressão , Hiperplasia Prostática/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/metabolismo , Sulfonamidas/administração & dosagem , Tansulosina
14.
Spine J ; 15(5): 866-74, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25638495

RESUMO

BACKGROUND CONTEXT: Diabetes is present in 5% to 20% of patients undergoing spine surgeries and is a known risk factor for reoperation. Considering the chronicity of diabetes, its influence on the reoperation rate may differ over time. PURPOSE: To present the relationship between diabetes and the reoperation rate over time. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: A national health insurance database was used to identify a cohort of patients who underwent an initial surgery for lumbar degenerative disease in 2003 (n=34,918). OUTCOME MEASURES: The primary end point was any type of second lumbar surgery after fusion surgery (n=4,792) or decompression surgery (n=30,126) during the early (0-postoperative 90 days), short-term (91-365 days), and midterm (1-6 years) periods. METHODS: All patients were followed up until December 2008. Cox proportional hazards regression modeling was used to assess the adjusted reoperation rates in the diabetic patients. RESULTS: The incidence of diabetes in the present cohort was 24.5% in the fusion group and 16.9% in the decompression group. Overall, reoperation was performed in 13.2% (631 of 4,792) of the patients after fusion surgery and in 14.0% (4,214 of 30,126) of the patients after decompression surgery. After fusion surgery, diabetes did not make a significant difference in the reoperation rate during the entire follow-up period. After decompression surgery, the reoperation rate was not different during Postoperative Month 3, but diabetic patients showed a 1.2 to 1.4 times higher reoperation rate during postoperative 3 months to 5 years (p<.01). CONCLUSIONS: The study did not find a relationship between diabetes at the time of surgery and the reoperation rate during the early postoperative period. Thereafter, the reoperation rate was not higher after fusion surgery in diabetic patients, but it was higher after decompression surgery.


Assuntos
Descompressão Cirúrgica/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Região Lombossacral/cirurgia , Fusão Vertebral/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
15.
Dis Markers ; 35(6): 679-85, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24311892

RESUMO

BACKGROUND AND AIM: It is well known that androgen deprivation relates to penile fibrosis, so we hypothesize that long-term treatment with 5-alphareductase inhibitors (5ARIs) may increase the risk of fibrosis of prostate. PATIENTS AND METHODS: Thirty-two BPH patients who underwent transurethral resection of the prostate were enrolled. The patients were divided into two groups: group one, 16 patients underwent TURP who had been treated with tamsulosin for 2 years; group two, 16 patients underwent TURP who had been treated with combination of tamsulosin and dutasteride for at least 1 year. We evaluated the expressions of nNOS, iNOS, eNOS, TGF-ß1, TGF-ß2, phosphorylated-Smad2/3 (p-Smad2/3), E-cadherin, N-cadherin, and α-smooth muscle actin in the resected prostate tissues by western blotting, and the TGF-ß concentration was determined by ELISA kit. RESULTS: The expressions of 3 isoforms of NOS were significantly increased in group 2 except of eNOS in lateral prostate, and the expressions of TGF-ß1, TGF-ß2, and p-Smad2/3 increased about 2-fold compared with group 1. In group 2, the E-cadherin expression decreased while N-cadherin expression increased significantly. CONCLUSIONS: The overexpression of nNOS may contribute to prostate smooth muscle relaxation; however, long-time treatment with 5 ARI increases the risk of fibrosis of prostate.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Hiperplasia Prostática/metabolismo , Sulfonamidas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Inibidores de 5-alfa Redutase/uso terapêutico , Antígenos CD/metabolismo , Caderinas/metabolismo , Terapia Combinada , Humanos , Hipertrofia/metabolismo , Masculino , Óxido Nítrico Sintase/metabolismo , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Próstata/cirurgia , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Sulfonamidas/uso terapêutico , Tansulosina , Ressecção Transuretral da Próstata
16.
Asian J Androl ; 15(1): 134-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23147465

RESUMO

The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum (PCC) was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits (2.5-3.0 kg) were precontracted with phenylephrine (Phe, 10 µmol l(-1)) and then treated with various concentrations of Cuscuta chinensis extract (1, 2, 3, 4 and 5 mg ml(-1)). The change in penile tension was recorded, and cyclic nucleotides in the PCC were measured by radioimmunoassay (RIA). The interaction between Cuscuta chinensis and sildenafil was also evaluated. The result indicated that the PCC relaxation induced by Cuscuta chinensis extract was concentration-dependent. Pre-treatment with an nitric oxide synthase (NOS) inhibitor (Nω nitro-L-arginine-methyl ester, L-NAME), a guanylyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ), or a protein kinase A inhibitor (KT 5720) did not completely inhibit the relaxation. Incubation of penile cavernous tissue with the Cuscuta chinensis extract significantly increased cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in the PCC. Moreover, the Cuscuta chinensis extract significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP pathway, and it may improve erectile dysfunction (ED), which does not completely respond to sildenafil citrate.


Assuntos
Cuscuta/química , Disfunção Erétil/tratamento farmacológico , Relaxamento Muscular/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/fisiologia , Fitoterapia , Extratos Vegetais/farmacologia , Animais , GMP Cíclico/fisiologia , Inibidores Enzimáticos/farmacologia , Interações Ervas-Drogas , Masculino , Músculo Liso/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Piperazinas/farmacologia , Purinas/farmacologia , Coelhos , Citrato de Sildenafila , Sulfonas/farmacologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-22727101

RESUMO

OBJECTIVES: This study aimed to assess the hard and soft tissue changes in osteomyelitis (OM) of the jaws using CT images. STUDY DESIGN: The CT images of 153 patients (59 males and 94 females) with OM of the jaws were retrospectively reviewed. The relationships between each space involvement, between space and muscle involvements, between cortical bone defect and space involvement, and between cortical bone defect and muscle involvement were evaluated. RESULTS: The cortical bone defect was more common on the buccal side in the maxilla and on the lingual side in the mandible. The most commonly involved muscle was the buccinator muscle in the maxilla and the masseter muscle in the mandible and the most frequently involved space was the buccal space followed by the masticator space. CONCLUSIONS: CT is a useful tool in evaluating both hard and soft tissue changes of OM of the jaws.


Assuntos
Doenças Mandibulares/diagnóstico por imagem , Doenças Maxilares/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Criança , Meios de Contraste , Feminino , Humanos , Iohexol/análogos & derivados , Masculino , Doenças Mandibulares/patologia , Doenças Maxilares/patologia , Pessoa de Meia-Idade , Osteomielite/patologia , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
18.
Phytother Res ; 26(6): 800-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22072532

RESUMO

The objective of this study was to evaluate the effect and mechanism of capillarisin from Artemisia capillaris (A. capillaris) on rabbit penile corpus cavernosum (PCC). The pre-contracted New Zealand White rabbit (2.5-3.0 kg) penis with phenylephrine (Phe; 10⁻5 M) was treated with various concentrations of ethanol extract of A. capillaris (0.1, 0.5, 1, and 2 mg/mL) and capillarisin, the active component of A. capillaris (10⁻7, 10⁻6, 10⁻5 and 10⁻4 M). Capillarisin was also applied to PCC tissues contracted with Phe, which were pre-incubated with phosphodiesterase type 5 inhibitors (PDE5 Is). Cyclic nucleotides in the perfusate were measured by radioimmunoassay. The tissues were pre-incubated with Nω nitro-l-arginine-methyl ester (L-NAME, 10⁻³ M) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10⁻5 M) to block nitric oxide (NO) synthase and guanylate cyclase, respectively. Capillarisin induced penile relaxation and enhanced PDE5 Is-induced relaxation. Capillarisin increased cGMP and cAMP in the perfusate. The application of capillarisin on PCC pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Capillarisin exerts the relaxing effect on PCC by activating the NO-cGMP and adenylyl cAMP signaling pathways and may become an alternative medicine for patients who want to use natural products to improve erectile function or do not completely respond to PDE5 Is.


Assuntos
Artemisia/química , Cromonas/farmacologia , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Animais , Cromonas/administração & dosagem , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Avaliação Pré-Clínica de Medicamentos , Etanol , Masculino , Relaxamento Muscular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Oxidiazóis/farmacologia , Fenilefrina/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quinoxalinas/farmacologia , Coelhos , Radioimunoensaio , Transdução de Sinais
19.
Int J Syst Evol Microbiol ; 59(Pt 12): 3030-4, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19643903

RESUMO

A Gram-negative, aerobic, rod-shaped, motile, marine bacterium, strain AR11(T), was isolated from Arctic marine sediment. Strain AR11(T) grew with 0.5-7 % NaCl and at 7-37 degrees C and pH 5.5-9.0. It utilized propionate, 3-hydroxybenzoate, l-proline, acetate, d- and l-lactate, l-alanine, malate and phenylacetic acid. Alkaline phosphatase, esterase lipase (C8), leucine arylamidase and acid phosphatase activity tests were positive. Acid was produced from 5-ketogluconate and aesculin. Strain AR11(T) possessed C(16 : 0) (22.0 %), summed feature 4 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH; 28.1 %) and summed feature 7 (one or more of C(18 : 1)omega7c, omega9t and omega12t; 34.0 %) as the major cellular fatty acids. The major ubiquinone was Q-8. Comparative 16S rRNA gene sequence studies showed that strain AR11(T) belonged to the Gammaproteobacteria and was most closely related to Marinobacterium stanieri DSM 7027(T), Marinobacterium halophilum mano11(T) and Marinobacterium georgiense KW-40(T) (97.8, 97.0 and 96.7 % similarity, respectively). The G+C content of the genomic DNA of strain AR11(T) was 57.9 mol%. DNA-DNA relatedness data indicated that strain AR11(T) represented a distinct species that was separated from M. stanieri DSM 7027(T), M. halophilum KCTC 12240(T) and M. georgiense JCM 21667(T). On the basis of evidence from this polyphasic study, it is proposed that strain AR11(T) (=KCTC 22254(T)=JCM 15134(T)) represents the type strain of a novel species, Marinobacterium maritimum sp. nov.


Assuntos
Alteromonadaceae/classificação , Alteromonadaceae/isolamento & purificação , Sedimentos Geológicos/microbiologia , Água do Mar/microbiologia , Alteromonadaceae/genética , Alteromonadaceae/metabolismo , Regiões Árticas , DNA Bacteriano/genética , DNA Ribossômico/genética , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética
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