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1.
Urolithiasis ; 52(1): 88, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874649

RESUMO

Urinary infectious stones are challenging due to bacterial involvement, necessitating a comprehensive understanding of these conditions. Antibiotic-resistant urease-producing bacteria further complicate clinical management. In this study, analysis of urine and stone samples from urinary tract infection (UTI) patients revealed microbial shifts, gene enrichment in stones, and metabolic pathway disparities; antibiotic resistance gene trends were phylum-specific, urease-producing bacteria are at risk of acquiring AMR carried by Enterobacteriaceae under antibiotic, emphasizing potential AMR dissemination between them; Correlations of key pathogenic species in kidney stone and urine microbial communities highlight the need for targeted therapeutic strategies to manage complexities in UTIs; Stones and urine contain a variety of deleterious genes even before antibiotic use, and piperacillin/tazobactam better reduced the abundance of antibiotic resistance genes in stones and urine. The presence of diverse antibiotic resistance and virulence genes underscores challenges in clinical management and emphasizes the need for effective treatment strategies to mitigate risks associated with UTIs and urinary infectious stone formation. Ongoing research is vital for advancing knowledge and developing innovative approaches to address these urological conditions.


Assuntos
Infecções Urinárias , Fatores de Virulência , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Humanos , Fatores de Virulência/genética , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Microbiota/efeitos dos fármacos , Microbiota/genética , Farmacorresistência Bacteriana/genética , Cálculos Urinários/microbiologia , Cálculos Urinários/genética , Feminino , Masculino , Resistência Microbiana a Medicamentos/genética
2.
Front Endocrinol (Lausanne) ; 15: 1301703, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476671

RESUMO

Background: Insulin resistance has been proven to be associated with renal cell carcinoma (RCC). However, the prognostic value of the triglyceride-glucose (TyG) index, as a marker for insulin resistance (IR), is still unclear. Therefore, we conducted research to explore the prognostic value and the predictive performance of the TyG index in postoperative RCC patients. Methods: A total of 651 postoperative RCC patients from January 2016 to June 2018 were enrolled in the final study. Their clinical and laboratory parameters were collected from medical records and through follow-up by phone. The triglyceride-glucose (TyG) index was calculated as follows: TyG = Ln[TG (mg/dl) × FBG (mg/dL)/2]. The overall survival (OS) and disease-free survival (DFS) were identified as the main outcomes. Results: The TyG index is an independent prognostic factor for OS (HR = 2.340, 95% CI = 1.506 to 3.64, P < 0.001) and DFS (HR = 2.027, 95% CI = 1.347 to 3.051, P < 0.001) in postoperative RCC patients. Kaplan-Meier survival curves of the different TyG index levels showed statistically significant differences in terms of OS and DFS (log-rank test, P < 0.0001). Furthermore, the TyG index was significantly associated with RCC risk factors. Conclusion: The TyG index is significantly associated with RCC survival. The mechanisms responsible for these results may contribute toward the improvement of RCC prognosis and immunotherapy efficacy and the development of new immunotherapeutic targets.


Assuntos
Carcinoma de Células Renais , Resistência à Insulina , Neoplasias Renais , Humanos , Estudos Retrospectivos , Prognóstico , Glucose , Triglicerídeos
3.
Cancer Cell Int ; 23(1): 300, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017469

RESUMO

BACKGROUNDS: Glucose metabolism is associated with the development of cancers, and m6A RNA methylation regulator-related genes play vital roles in bladder urothelial carcinoma (BLCA). However, the role of m6A-related glucose metabolism genes in BLCA occurrence and development has not yet been reported. Our study aims to integrate m6A- and glycolysis-related genes and find potential gene targets for clinical diagnosis and prognosis of BLCA patients. METHODS: Sequencing data and clinical information on BLCA were extracted from common databases. Univariate Cox analysis was used to screen prognosis-related m6A glucose metabolism genes; BLCA subtypes were distinguished using consensus clustering analysis. Subsequently, genes associated with BLCA occurrence and development were identified using the "limma" R package. The risk score was then calculated, and a nomogram was constructed to predict survival rate of BLCA patients. Functional and immune microenvironment analyses were performed to explore potential functions and mechanisms of the different risk groups. RESULTS: Based on 70 prognosis-related m6A glucose metabolism genes, BLCA was classified into two subtypes, and 34 genes associated with its occurrence and development were identified. Enrichment analysis revealed an association of genes in high-risk groups with tricarboxylic acid cycle function and glycolysis. Moreover, significantly higher levels of seven immune checkpoints, 14 immune checkpoint inhibitors, and 32 immune factors were found in high-risk score groups. CONCLUSIONS: This study identified two biomarkers associated with BLCA prognosis; these findings may deepen our understanding of the role of m6A-related glucose metabolism genes in BLCA development. We constructed a m6A-related glucose metabolism- and immune-related gene risk model, which could effectively predict patient prognosis and immunotherapy response and guide individualized immunotherapy.

4.
Front Immunol ; 14: 1283792, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954600

RESUMO

Introduction: Tryptophan metabolism is indirectly involved in immune tolerance and promotes response to anticancer drugs. However, the mechanisms underlying tryptophan metabolism and immune landscape in bladder urothelial carcinoma (BLCA) are not fully understood. Methods: A BLCA dataset containing 406 tumor samples with clinical survival information and 19 normal samples were obtained from the Cancer Genome Atlas database. The validation set, GSE32894, contained 223 BLCA tumor samples with survival information, and the single-cell dataset, GSE135337, included seven BLCA tumor samples; both were obtained from the gene expression omnibus database. Univariate and multivariate Cox regression analyses were conducted to evaluate clinical parameters and risk scores. Immune infiltration and checkpoint analyses were performed to explore the immune landscape of BLCA. Single-cell analysis was conducted to further identify the roles of model genes in BLCA. Finally, NAMPT expression in BLCA and adjacent tissues was detected using RT-qPCR, CCK-8 and Transwell assays were conducted to determine the role of NAMPT in BLCA cells. Results: Six crossover genes (TDO2, ACAT1, IDO1, KMO, KYNU, and NAMPT) were identified by overlap analysis of tryptophan metabolism-related genes, immune-related genes, and differentially expressed genes (DEGs). Three biomarkers, NAMPT, IDO1, and ACAT1, were identified using Cox regression analysis. Accordingly, a tryptophan metabolism- and immune-related gene risk model was constructed, and the patients were divided into high- and low-risk groups. There were significant differences in the clinical parameters, prognosis, immune infiltration, and immunotherapy response between the risk groups. RT-qPCR revealed that NAMPT was upregulated in BLCA samples. Knocking down NAMPT significantly inhibited BLCA cell proliferation, migration, and invasion. Discussion: In our study, we constructed a tryptophan metabolism- and immune-related gene risk model based on three biomarkers, namely NAMPT, IDO1, and ACAT1, that were significantly associated with the progression and immune landscape of BLCA. The risk model could effectively predict patient prognosis and immunotherapy response and can guide individualized immunotherapy.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Triptofano , Bexiga Urinária , Triptofano Oxigenase , Biomarcadores
5.
J Cell Commun Signal ; 17(4): 1323-1333, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37249822

RESUMO

Studies have shown that tripartite motif-containing (TRIM) family proteins function as E3 ubiquitin ligases and play essential roles in cancer biology. In the present study, we validated a contribution of TRIM9 to bladder cancer progression. 296 patients derived from The Cancer Genome Atlas (TCGA) database and 22 clinical specimens were included, in which accumulated TRIM9 correlated with the poor prognosis and higher relapse in bladder patients. In vitro, TRIM9 promoted bladder cancer cells Biu-87 and T24 cell proliferation and migration. Meanwhile, overexpression of TRIM9 reduced the chemosensitivity in Biu-87 and T24 to mitomycin C (MMC) and gemcitabine (GEM). As an underlying mechanism, we found that TRIM9 stimulated carcinoembryonic antigen 6 (CEACAM6) upregulation, which further facilitated Smad2/3-matrix metalloproteinase 2 (MMP2) signaling activation both in vitro and in vivo. Those results indicated that TRIM9 facilitated bladder cancer development and chemoresistance by CEACAM6-Smad2/3 axis. TRIM9 and its associated molecules could be a potential diagnostic indicator and therapeutic target in bladder cancer.

6.
J Surg Case Rep ; 2022(4): rjac185, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35495080

RESUMO

Mucinous tubule and spindle cell carcinoma (MTSCC) of the kidney is a rare renal pleomorphic tumor considered as low-grade malignant, with occurring mainly in female. Few mucin-poor MTSCC cases have been reported so far. A typical MTSCC is composed of closely arranged tubules with pale mucus matrix and spindle cell components. Mucin-poor MTSCC is difficult to distinguish from other renal cell carcinomas due to small amount of mucus. We reported a case of mucin-poor MTSCC in a 37-year-old male with detailed imaging, histology, immunohistochemical and next-generation sequencing information, looking forward to providing an insight into mucin-poor MTSCC.

7.
PeerJ ; 10: e12724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35127282

RESUMO

PURPOSE: To investigate the mechanism of miR-148a-3p regulating the proliferation and migration of bladder tumor cells. MATERIALS AND METHODS: We conducted a preliminary study to detect the relative expression of miR-148a-3p in bladder cancer and para-cancerous tissue samples. Three bladder tumor cell lines, T24, 5,637 and UM-UC-3, were selected. The expression levels of miR-148a-3p were artificially regulated with miR-148a-3p mimics and the miR-148a-3p inhibitor. The relative expression levels of miR-148a-3p in the samples of each cell line were determined. Cell Counting Kit-8 (CCK-8) was used to detect cell proliferation, while the effect of the miR-148a-3p mimics and inhibitor on tumor cell migration was detected by wound healing assay. Flow cytometry assay was carried out to explore the effect of miR-148a-3p on cell apoptosis. Dual-luciferase reporter assay was performed in order to verify miR-148a-3p's target gene. The expressions of ROCK-1 and Bcl-2 were analyzed by western blot. RESULTS: The relative expression of miR-148a-3p in tumor and adjacent tissues was assessed with qRT-PCR (P < 0.05) and found to be significantly lower in the tumor tissues than the adjacent tissues. The data obtained from the CCK-8 and wound healing assay showed that intracellular transfection of miR-148a-3p mimics could inhibit cell proliferation and migration, while the miR-148a-3p inhibitor promoted them. Overexpression of miR-148a-3p promoted cell apoptosis in the T24 and 5,637 cell lines. The dual-luciferase reporter assay verified that ROCK-1 is a direct target of miR-148a-3p. Western blot showed that miR-148a-3p overexpression downregulated the expression of ROCK-1 and Bcl-2, while miR-148a-3p knockdown upregulated the expression of ROCK-1 and Bcl-2. CONCLUSIONS: We confirmed that miR-148a-3p was significantly decreased in bladder cancer cells. miR-148a-3p overexpression inhibited bladder cancer cell proliferation and migration, whereas miR-148a-3p knockdown promoted bladder cancer cell proliferation and migration. Moreover, we found that ROCK-1 was a downstream target of miR-148a-3p. We also found that miR-148a-3p induced cell apoptosis by regulating the expression of Bcl-2. However, the deeper mechanism of this regulatory relationship needs further study.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Receptores Proteína Tirosina Quinases , Neoplasias da Bexiga Urinária/genética , Quinases Associadas a rho
8.
Cancer Sci ; 113(4): 1250-1263, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35048477

RESUMO

Circular RNAs (circRNAs) are key regulatory factors in the development of multiple cancers. This study is targeted at exploring the effect of circ_0002623 on bladder cancer (BCa) progression and its mechanism. Circ_0002623 was screened out by analyzing the expression profile of circRNAs in BCa tissues. Circ_0002623, miR-1276, and SMAD2 mRNA expression levels in clinical sample tissues and cell lines were detected through quantitative real-time polymerase chain reaction (qRT-PCR). After circ_0002623 had been overexpressed or silenced in BCa cells, the cell proliferation, migration, and cell cycle were evaluated by CCK-8, BrdU, Transwell assay, and flow cytometry. Tumor xenograft model was used to validate the biological function of circ_0002623 in vivo. Bioinformatics analysis and dual-luciferase reporter gene assay were conducted for analyzing and confirming, respectively, the targeted relationship between circ_0002623 and miR-1276, as well as between miR-1276 and SMAD2. The regulatory effects of circ_0002623 and miR-1276 on the expression levels of TGF-ß, WNT1, and SMAD2 in BCa cells were detected by Western blot. We reported that, in BCa tissues and cell lines, circ_0002623 was upregulated, whereas miR-1276 was downregulated. Circ_0002623 positively regulated BCa cell proliferation, migration, and cell cycle progression. Additionally, circ_0002623 could competitively bind with miR-1276 to increase the expression of SMAD2, the target gene of miR-1276. Furthermore, circ_0002623 could regulate the expression of TGF-ß and WNT1 via modulating miR-1276 and SMAD2. This study helps to better understand the molecular mechanism underlying BCa progression.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Proteína Smad2/genética , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Neoplasias da Bexiga Urinária/patologia
10.
Oncol Lett ; 20(1): 501-508, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32565975

RESUMO

The aim of the present study was to preoperatively predict renal function following partial nephrectomy (PN) using an imaging-based approach and to examine the correlation between preoperatively predicted and postoperatively observed renal function in the study cohort. A total of 128 consecutive patients who underwent PN between May 2015 and March 2018 and had available clinical data were included in this study. A hand-scripting method was used to estimate the defected volume (Vdef) from preoperative computerized tomography scans, whereas a cylindrical method was used to obtain preoperative renal volume (Vpre). The function index (FI) was proposed as a new term to estimate preserved parenchyma percentage following PN. The FI was defined as f=(Vpre-Vdef)/Vpre for the operated kidney and adjusted as FI=0.5 × (f + 1) for the bilateral kidneys. The estimated glomerular filtration rates (GFRs) before surgery, one day after surgery and ~12 months after surgery were calculated using the Modification of Diet in Renal Disease Study equation. The GFR rate after PN was predicted by multiplying the preoperative GFR by the FI. The predictive role of the FI was further tested using multiple linear regression and correlation analyses. The median FI in the present study was 94% for unilateral kidney surgery and adjusted to 97% for bilateral kidneys. Linear correlation analysis revealed that the predicted GFR significantly correlated with the observed immediate postoperative GFR (R2, 0.594) and observed late postoperative GFR (R2, 0.828). In multivariate regression analysis, preoperative GFR (P<0.01) and warm ischemic time (P<0.01) were identified as independent determinants of the immediate postoperative renal function, whereas only FI (P<0.01) and preoperative GFR (P<0.01) were identified as independent determinants of late renal function after PN. The preoperatively predicted renal function using an imaging-based approach had a significant positive correlation with the postoperatively observed renal function. The FI estimated from the preoperative diagnostic images in the present study was identified as an independent determinant of long-term renal function after PN.

11.
Exp Ther Med ; 15(1): 1053-1061, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29403553

RESUMO

Oxidative stress is closely associated with the onset of diabetes mellitus (DM). Diabetic urethropathy is one of the most common complications of DM, but few studies have been conducted to investigate the role of oxidative stress in diabetic urethropathy. Grape seed proanthocyanidin extract (GSPE) has been previously reported to reduce oxidative injury. The present study aimed to investigate the role of oxidative stress and the protective effects of GSPE on urethral dysfunction using a streptozotocin-induced DM rat model. Female Wistar rats were divided into a control group (n=36), a DM group (n=36) and a DM + GSPE group (n=36). Urodynamic testing was performed using a PowerLab data acquisition device. The expression of neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine and nuclear factor erythroid 2-related factor 2 (Nrf2) was determined using western blot analysis. The expression of 3-nitrotyrosine was also determined using immunohistochemistry. Nitric oxide (NO), cyclic guanosine monophosphate (cGMP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial ELISA kits. A significant increase was observed in the intravesical pressure thresholds for inducing urethral relaxation and the urethral perfusion pressure nadir in DM rats compared with the control group. GSPE was observed to reverse the increase of these parameters compared with the DM group. In addition, GSPE could reverse the downregulation of nNOS, NO and cGMP expression, and the decreased activities of antioxidant enzymes (SOD and GSH-Px). GSPE reversed the upregulation of 3-nitrotyrosine and MDA in DM rats. GSPE also activated Nrf2, which is a key antioxidative transcription factor. The findings of the present study demonstrated that GSPE protects urethra function in DM rats through modulating the NO-cGMP signaling pathway. The protective roles of GSPE may be associated with activation of the Nrf2 defense pathway.

12.
Neurourol Urodyn ; 36(5): 1270-1277, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27571328

RESUMO

AIMS: To investigate the effects of electrical stimulation of sacral dorsal/ventral roots on irritation-induced bladder overactivity, reveal possible different mechanisms under nociceptive bladder conditions, and establish a large animal model of sacral neuromodulation. METHODS: Intravesical infusion of 0.5% acetic acid (AA) was used to irritate the bladder and induce bladder overactivity in cats under α-chloralose anesthesia. Electrical stimulation (5, 15, or 30 Hz) was applied to individual S1-S3 dorsal or ventral roots at or below motor threshold intensity. Repeated cystometrograms (CMGs) were performed with/without the stimulation to determine the inhibition of bladder overactivity. RESULTS: AA irritation induced bladder overactivity and significantly (P < 0.05) reduced the bladder capacity to 62.6 ± 11.7% of control capacity measured during saline CMGs. At threshold intensity for inducing reflex twitching of the anal sphincter or toe, S1/S2 dorsal root stimulation at 5 Hz but not at 15 or 30 Hz inhibited bladder overactivity and significantly (P < 0.05) increased bladder capacity to 187.3 ± 41.6% and 155.5 ± 9.7% respectively, of AA control capacity. Stimulation of S3 dorsal root or S1-S3 ventral roots was not effective. Repeated stimulation of S1-S3 dorsal root did not induced a post-stimulation inhibition. CONCLUSIONS: This study established a cat model of sacral neuromodualation of nociceptive bladder overactivity. The results revealed that the mechanisms underlying sacral neuromodulation are different for nociceptive and non-nociceptive bladder activity.


Assuntos
Terapia por Estimulação Elétrica/métodos , Sacro/fisiopatologia , Raízes Nervosas Espinhais/fisiopatologia , Bexiga Urinária Hiperativa/terapia , Ácido Acético , Animais , Gatos , Modelos Animais de Doenças , Feminino , Masculino , Reflexo/fisiologia , Bexiga Urinária Hiperativa/induzido quimicamente , Bexiga Urinária Hiperativa/fisiopatologia
13.
Neurourol Urodyn ; 36(6): 1496-1502, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27778372

RESUMO

AIMS: To determine the spinal segmental afferent contributions to tibial and pudendal inhibition of bladder overactivity. METHODS: Intravesical infusion of 0.5% acetic acid was used to irritate the bladder and induce bladder overactivity in anesthetized cats. Tibial or pudendal nerve stimulation was used to suppress the bladder overactivity and increase bladder capacity during cystometry. L5-S3 dorsal roots ipsilateral to the stimulation were exposed by a laminectomy and transected sequentially during the experiments to determine the role of individual dorsal roots in tibial or pudendal neuromodulation. RESULTS: Transection of L5 dorsal root had no effect. Transection of L6 dorsal root in four cats produced an average 18% reduction in tibial inhibition, which is not a significant change when averaged in the group of 10 cats. Transection of L7 dorsal root completely removed the tibial inhibition without changing reflex bladder activity or pudendal inhibition. Transection of S1 dorsal root reduced the pudendal inhibition, after which transection of S2 dorsal root completely removed the pudendal inhibition. Transection of S3 dorsal root had no effect. The control bladder capacity was increased only by transection of S2 dorsal root. CONCLUSIONS: This study in cats revealed that tibial and pudendal neuromodulation of reflex bladder overactivity depends on activation of primary afferent pathways that project into different spinal segments. This difference may be related to the recent observation in cats that the two types of neuromodulation have different mechanisms of action.


Assuntos
Nervo Pudendo/fisiopatologia , Nervo Tibial/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Ácido Acético , Animais , Gatos , Modelos Animais de Doenças , Feminino , Masculino , Raízes Nervosas Espinhais/fisiopatologia , Bexiga Urinária Hiperativa/induzido quimicamente
14.
Neuromodulation ; 20(1): 81-87, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27730701

RESUMO

OBJECTIVE: To determine the role of opioid, ß-adrenergic, and metabotropic glutamate 5 receptors in sacral neuromodulation of bladder overactivity. MATERIAL AND METHODS: In α-chloralose anesthetized cats, intravesical infusion of 0.5% acetic acid (AA) irritated the bladder and induced bladder overactivity. Electric stimulation (5 Hz, 0.2 ms, 0.16-0.7V) of S1 or S2 sacral dorsal roots inhibited the bladder overactivity. Naloxone, propranolol, or MTEP were given intravenously (i.v.) to determine different neurotransmitter mechanisms. RESULTS: AA significantly (p < 0.05) reduced bladder capacity to 7.7 ± 3.3 mL from 12.0 ± 5.0 mL measured during saline infusion. S1 or S2 stimulation at motor threshold intensity significantly (p < 0.05) increased bladder capacity to 179.4 ± 20.0% or 219.1 ± 23.0% of AA control, respectively. Naloxone (1 mg/kg) significantly (p < 0.001) reduced the control capacity to 38.3 ± 7.3% and the bladder capacity measured during S1 stimulation to 106.2 ± 20.8% of AA control, but did not significantly change the bladder capacity measured during S2 stimulation. Propranolol (3 mg/kg) significantly (p < 0.01) reduced bladder capacity from 251.8 ± 32.2% to 210.9 ± 33.3% during S2 stimulation, but had no effect during S1 stimulation. A similar propranolol effect also was observed in naloxone-pretreated cats. In propranolol-pretreated cats during S1 or S2 stimulation, MTEP (3 mg/kg) significantly (p < 0.05) reduced bladder capacity and naloxone (1 mg/kg) following MTEP treatment further reduced bladder capacity. However, a significant inhibition could still be induced by S1 or S2 stimulation after all three drugs were administered. CONCLUSIONS: Neurotransmitter mechanisms in addition to those activating opioid, ß-adrenergic, and metabotropic glutamate 5 receptors also are involved in sacral neuromodulation.


Assuntos
Neurotransmissores/metabolismo , Estimulação da Medula Espinal/métodos , Raízes Nervosas Espinhais/fisiologia , Bexiga Urinária Hiperativa/metabolismo , Bexiga Urinária Hiperativa/terapia , Ácido Acético/toxicidade , Antagonistas Adrenérgicos beta/uso terapêutico , Análise de Variância , Animais , Gatos , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Feminino , Indicadores e Reagentes/toxicidade , Masculino , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Propranolol/uso terapêutico , Piridinas/uso terapêutico , Sacro , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/induzido quimicamente
15.
J Pharmacol Exp Ther ; 359(3): 436-441, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27729478

RESUMO

In α-chloralose-anesthetized cats, we examined the role of GABAA, glycine, and opioid receptors in sacral neuromodulation-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.5% acetic acid (AA). AA irritation significantly (P < 0.01) reduced bladder capacity to 59.5 ± 4.8% of saline control. S1 or S2 dorsal root stimulation at threshold intensity for inducing reflex twitching of the anal sphincter or toe significantly (P < 0.01) increased bladder capacity to 105.3 ± 9.0% and 134.8 ± 8.9% of saline control, respectively. Picrotoxin, a GABAA receptor antagonist administered i.v., blocked S1 inhibition at 0.3 mg/kg and blocked S2 inhibition at 1.0 mg/kg. Picrotoxin (0.4 mg, i.t.) did not alter the inhibition induced during S1 or S2 stimulation, but unmasked a significant (P < 0.05) poststimulation inhibition that persisted after termination of stimulation. Naloxone, an opioid receptor antagonist (0.3 mg, i.t.), significantly (P < 0.05) reduced prestimulation bladder capacity and removed the poststimulation inhibition. Strychnine, a glycine receptor antagonist (0.03-0.3 mg/kg, i.v.), significantly (P < 0.05) increased prestimulation bladder capacity but did not reduce sacral S1 or S2 inhibition. After strychnine (0.3 mg/kg, i.v.), picrotoxin (0.3 mg/kg, i.v.) further (P < 0.05) increased prestimulation bladder capacity and completely blocked both S1 and S2 inhibition. These results indicate that supraspinal GABAA receptors play an important role in sacral neuromodulation of bladder overactivity, whereas glycine receptors only play a minor role to facilitate the GABAA inhibitory mechanism. The poststimulation inhibition unmasked by blocking spinal GABAA receptors was mediated by an opioid mechanism.


Assuntos
Receptores de GABA-A/metabolismo , Receptores de Glicina/metabolismo , Receptores Opioides/metabolismo , Nervos Espinhais , Bexiga Urinária Hiperativa/metabolismo , Animais , Gatos , Estimulação Elétrica , Feminino , Masculino , Naloxona/farmacologia , Naloxona/uso terapêutico , Picrotoxina/farmacologia , Picrotoxina/uso terapêutico , Receptores de Glicina/antagonistas & inibidores , Nervos Espinhais/fisiopatologia , Estricnina/farmacologia , Estricnina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/fisiopatologia
16.
Can Urol Assoc J ; 10(9-10): E320-E323, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27695589

RESUMO

Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumours that derive from extra-adrenal chromaffin cells. Cushing's syndrome (CS) caused by paragangliomas is extremely rare. We report a 53-year-old man with hypertension, diabetes, and symptoms of hypokalemia. Computer tomography (CT) revealed two retroperitoneal masses and bilateral adrenal hyperplasia. Together with the laboratory examinations, ectopic CS caused by multiple paragangliomas was highly suspected. The patient underwent resections of retroperitoneal tumours, left kidney, and left adrenal; postoperative histopathology confirmed two paragangliomas that were both positively stained for adrenocorticotropic hormone (ACTH). He got clinical and biochemical recoveries without any recurrent evidence at the nine-month followup.

17.
Am J Physiol Renal Physiol ; 311(1): F78-84, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27170683

RESUMO

This study investigated the role of the hypogastric nerve and ß-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 184.7 ± 12.6% and 214.5 ± 10.4% of the control capacity. Propranolol (3 mg/kg iv) had no effect on PNS inhibition, but 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP; 1-3 mg/kg iv) significantly (P < 0.05) reduced the inhibition. During AA irritation, the control bladder capacity was significantly (P < 0.05) reduced to ∼22% of the saline control capacity. PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 406.8 ± 47% and 415.8 ± 46% of the AA control capacity. Propranolol significantly (P < 0.05) reduced the bladder capacity to 276.3% ± 53.2% (at 2T PNS) and 266.5 ± 72.4% (at 4T PNS) of the AA control capacity, whereas MTEP (a metabotropic glutamate 5 receptor antagonist) removed the residual PNS inhibition. Bilateral transection of the hypogastric nerves produced an effect similar to that produced by propranolol. This study indicates that hypogastric nerves and a ß-adrenergic mechanism in the detrusor play an important role in PNS inhibition of nociceptive but not non-nociceptive reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition.


Assuntos
Nociceptividade/fisiologia , Nervo Pudendo/fisiologia , Nervo Pudendo/fisiopatologia , Receptores Adrenérgicos beta/fisiologia , Reflexo/fisiologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Gatos , Denervação , Estimulação Elétrica , Feminino , Plexo Hipogástrico/fisiopatologia , Masculino , Piperidinas/farmacologia , Propranolol/farmacologia , Ratos , Receptores Adrenérgicos beta/efeitos dos fármacos , Tiazóis/farmacologia , Bexiga Urinária/efeitos dos fármacos
18.
Lasers Surg Med ; 48(5): 505-10, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26940981

RESUMO

BACKGROUND: The continuous wave 2-µm Thulium Laser has been introduced as potential technology with both high efficiency and safe practice; although little data have been shown regarding the long-term outcomes. OBJECTIVE: To analyze the long-term outcomes after thulium vaporesection of the prostate (ThuVaRP). METHODS: ThuVaRP was performed using the continuous wave, 2-µm Thulium: YAG laser at 70 W. The perioperative and post-operative follow-up data were analyzed. RESULTS: The average age at surgery was 71.5 (range 55-94 years). The median prostate size was 60.1 g (range 36.3-109.8 g). A median operation time was noted at 44.8 ± 6.5 minutes, while the median catheterization time was 3.5 ± 0.5 days. In regards to hospital stay, most patients had an average duration of 5.5 ± 1.5 days. Minor complications requiring non-interventional treatment happened in 237 (36.24%) of 654 patients, while major complications requiring re-interventions occurred in one patient (0.15%). During a 60-month follow-up, bladder neck fibrosis occurred in 1.22% of the patients. A BPH recurrence happened in 17 (2.60%) patients, of which 14 patients (2.14%) received a second surgery. In comparison to the pre-operative baseline, the patients Qmax, PVR volume, IPSS, and Qol scores all improved significantly (P < 0.01) at time of discharge. This continued into the post-operative follow-up visits (3-6-12-18-14-26-48-60 months). CONCLUSIONS: ThuVaRP is both an effective and safe treatment procedure for symptomatic BPO (with a low occurrence of complications). Lasers Surg. Med. 48:505-510, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
19.
Mol Clin Oncol ; 4(2): 143-150, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893850

RESUMO

Thyroid-like follicular carcinoma (TLFC) of the kidney is an extremely rare type of renal tumor, which has not been classified under a known subtype of renal cell carcinoma. It is histologically similar to the primary thyroid follicular carcinoma; however, the characteristics lack thyroid immunohistochemical markers. The aim of the present study was to illustrate the clinical characteristics of 3 new cases along with a review of the literature. The patients were compared with regards to gender, age, location and size of the tumor, imageology, morphology, immunohistochemistry and prognosis. According to the limited data, TLFC occurs mainly in young women and its clinical manifestations have no difference with other renal tumors. Its imageological features resemble a large spectrum of benign and malignant renal and extra-renal conditions, which should be eliminated in the diagnostic process. Confirmed diagnosis depends on the examination of pathology and immunohistochemistry. Surgical ablation is the preferred therapeutic method. Currently, TLFC has a relatively good prognosis; however, this conclusion requires further cases and long-term follow-ups. Improving the understanding of TLFC can help avoid misdiagnosis and prevent inappropriate treatment.

20.
J Neurophysiol ; 115(3): 1436-45, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26740534

RESUMO

This study aimed at understanding thermal effects on nerve conduction and developing new methods to produce a reversible thermal block of axonal conduction in mammalian myelinated nerves. In 13 cats under α-chloralose anesthesia, conduction block of pudendal nerves (n = 20) by cooling (5-30°C) or heating (42-54°C) a small segment (9 mm) of the nerve was monitored by the urethral striated muscle contractions and increases in intraurethral pressure induced by intermittent (5 s on and 20 s off) electrical stimulation (50 Hz, 0.2 ms) of the nerve. Cold block was observed at 5-15°C while heat block occurred at 50-54°C. A complete cold block up to 10 min was fully reversible, but a complete heat block was only reversible when the heating duration was less than 1.3 ± 0.1 min. A brief (<1 min) reversible complete heat block at 50-54°C or 15 min of nonblock mild heating at 46-48°C significantly increased the cold block temperature to 15-30°C. The effect of heating on cold block fully reversed within ∼40 min. This study discovered a novel method to block mammalian myelinated nerves at 15-30°C, providing the possibility to develop an implantable device to block axonal conduction and treat many chronic disorders. The effect of heating on cold block is of considerable interest because it raises many basic scientific questions that may help reveal the mechanisms underlying cold or heat block of axonal conduction.


Assuntos
Fibras Nervosas Mielinizadas/fisiologia , Condução Nervosa , Inibição Neural , Temperatura , Potenciais de Ação , Animais , Gatos , Feminino , Masculino , Contração Muscular , Músculo Estriado/inervação , Músculo Estriado/fisiologia , Uretra/inervação , Uretra/fisiologia
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