RESUMEN
BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.
Asunto(s)
Osteólisis , Animales , Cumarinas , Humanos , Ratones , Ratones Endogámicos C57BL , Osteólisis/inducido químicamente , Osteólisis/diagnóstico por imagen , Osteólisis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Proyectos de InvestigaciónRESUMEN
Acute lung injury (ALI) presents high mortality and morbidity clinically and by far no effective preventive strategy has been established. Extract of Ginkgo biloba leaves, EGb 761, is a complex mixture that possesses several clinical beneficial effects such as anti-oxidation, anti-inflammation, anti-tumor, and cardioprotective property. With EGb 761 pretreatment, both lipopolysaccharide (LPS)-induced protein leakage and neutrophil infiltration, and LPS-induced inflammatory responses including increased myeloperoxidase (MPO) activity, lipid peroxidation, and metalloproteinase (MMP)-9 activity, were inhibited; LPS-suppressed activation of antioxidative enzymes (AOE) were reversed; and not only the phosphorylation of NF-κB but also the degradation of its inhibitor, IκB, were suppressed. These results suggested that the protection mechanism of EGb 761 is by inhibition of NFκB activation, possibly via the up-regulation of antioxidative enzymes. More studies are needed to further evaluate whether EGb 761 is a suitable candidate as an effective dietary strategy to reduce the incidence of endotoxin-induced ALI.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/química , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Activación Enzimática/efectos de los fármacos , Ginkgo biloba , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Peroxidasa/metabolismo , Fitoterapia , Extractos Vegetales/farmacologíaRESUMEN
UNLABELLED: What's known on the subject? and What does the study add? Ovary hormone deficiency and the age-related changes in post-menopausal women are subjected to a number of urological dysfunctions, including overactive bladder syndrome. Green tea is a popular healthy drink worldwide and its extract catechin has strong anti-inflammatory and antioxidant properties. EGCG, the major type of catechin, is an antioxidant polyphenol flavonoid isolated from green tea. EGCG supplement could prevent ovariectomy-induced bladder dysfunction in a dose-related manner through its anti-oxidant, anti-fibrosis and anti-apoptosis effects. OBJECTIVE: To evaluate whether green tea extract, epigallocatechin gallate (EGCG), could prevent ovariectomy-induced overactive bladder (OAB) and to investigate its antioxidant, anti-apoptotic and anti-fibrosis effects. MATERIALS AND METHODS: In all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral ovariectomy, the first group served as the ovariectomy control, the second group received EGCG 1 µM/kg daily i.p. injection after ovariectomy surgery, and the third group received EGCG 10 µM/kg daily i.p. injection. The fourth group was taken as the sham without ovariectomy surgery. The rats were killed after 6 months after ovariectomy surgery. Cystometrograms were performed for the measure of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells. Western immunoblots were performed to determine the expressions of inflammatory markers, apoptosis-associated proteins and oxidative stress markers. RESULTS: Long-term ovariectomy significantly increased non-voiding contractions and decreased bladder compliance. Treatment with EGCG significantly increased bladder compliance and diminished non-voiding contractions. Ovariectomy significantly increased apoptotic cells and enhanced interstitial fibrosis in bladders. The expression of caspase-3 significantly increased, while that of Bcl-2 notably decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-ß, fibronectin and type I collagen expressions were significantly increased after 6 months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF-ß and type I collagen expressions. Oxidative stress markers, nitrotyrosine and protein carbonylation levels were significantly increased in the ovariectomy group. EGCG could attenuate this oxidative damage in dose-dependent fashion. CONCLUSIONS: Ovariectomy increased oxidative damage, enhanced voiding frequency and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and anti-apoptosis effects.
Asunto(s)
Antioxidantes/farmacología , Catequina/análogos & derivados , Menopausia/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Té , Vejiga Urinaria Hiperactiva/metabolismo , Animales , Catequina/farmacología , Modelos Animales de Enfermedad , Femenino , Ovariectomía , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: A rat model of ovariectomy-induced voiding dysfunction has been established, which mimicked the urge incontinence in postmenopausal women. Previous studies have identified strong anti-inflammatory/antioxidant properties of green tea and its associated polyphenols. The aim of this study was to evaluate whether the green tea extract, epigallocatechin gallate (EGCG), could prevent an ovariectomy-induced overactive bladder. METHODS: The study included 48 female Sprague-Dawley rats, which were divided into four groups. After bilateral ovariectomy during the following 6-month period, 12 rats received an intraperitoneal injection of saline, 24 rats received either a low-dose (1 µM kg(-1) d(-1)) or a high-dose (10 µM kg(-1) d(-1)) EGCG intraperitoneal injection. The sham group consisted of twelve rats that were not ovariectomized. In vivo isovolumetric cystometrograms were performed in all groups before the animals were euthanized. The immunofluorescence study used neurofilament stains to evaluate intramural nerve damage. Western immunoblots and real-time polymerase chain reaction were performed to determine M2 and M3 muscarinic cholinergic receptors (MChRs) at both protein and messenger RNA (mRNA) expressions. RESULTS: Long-term ovariectomy significantly increased non-voiding contractions, whereas treatment with EGCG significantly attenuated the frequency of non-voiding contractions. Ovariectomy significantly decreased the numbers of neurofilament and increased M2 and M3 MChR protein and mRNA expressions. Treatment with EGCG restored the amount of neurofilament staining and decreased M2 and M3 MChR protein and mRNA overexpressions. CONCLUSIONS: This study confirmed that ovary hormone deficiency induced overactive bladder dysfunction via intramural nerve damage and muscarinic receptor overexpression. EGCG prevented ovariectomy-induced bladder dysfunction through neuroprotective effects in a dose-dependent fashion.
Asunto(s)
Catequina/análogos & derivados , Menopausia/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Ovariectomía/efectos adversos , Té , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/etiología , Animales , Catequina/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Ratas , Ratas Sprague-Dawley , Receptor Muscarínico M2/biosíntesis , Receptor Muscarínico M3/biosíntesisRESUMEN
PURPOSE: Recent evidence indicates that ischemia and reperfusion are major etiological factors in the bladder dysfunction that occurs after partial bladder outlet obstruction. Coenzyme Q10 and alpha-lipoic acid are found naturally in mitochondria and act as potent antioxidants. We investigated the beneficial effects of coenzyme Q10 plus alpha-lipoic acid in a rabbit model of bladder outlet obstruction. MATERIALS AND METHODS: Twenty male rabbits were divided into 5 groups. Group 1 served as control and group 2 received three weeks of coenzyme Q10 plus alpha-lipoic acid supplementation. Rabbits in group 3 underwent surgical partial bladder outlet obstruction for duration of four weeks and groups 4 and 5 were obstructed for seven weeks. In group 5, coenzyme Q10 plus alpha-lipoic acid supplementation was given following 4 weeks obstruction and continued till the end of the seven weeks. The contractile responses to various agents were determined. The protein nitration and carbonylation levels were studied by immunoblotting. Nerve function was determined by choline acetyltransferase activity and nerve density. RESULTS: The contractile responses to different forms of stimulations, including field stimulation, ATP, carbachol and KCl all showed decreases following 4 and 7 weeks obstruction. Treatment with coenzyme Q10 plus alpha-lipoic acid significantly restored contractile responses to all forms of stimulation. Treatment also had mitochondrial and neuronal effects and reduced protein nitration and carbonylation. Histologically there was less detrusor muscle hypertrophy. CONCLUSIONS: The current study clearly demonstrates that coenzyme Q10 and alpha-lipoic acid supplementation can improve bladder function after outlet obstruction.
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Contracción Muscular/efectos de los fármacos , Ácido Tióctico/farmacología , Ubiquinona/análogos & derivados , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Obstrucción del Cuello de la Vejiga Urinaria/patología , Análisis de Varianza , Animales , Western Blotting , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Inmunohistoquímica , Masculino , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Probabilidad , Conejos , Distribución Aleatoria , Sensibilidad y Especificidad , Ubiquinona/farmacologíaRESUMEN
PURPOSE: Ischemia, reperfusion, and free radical generation have been recently implicated in the progressive bladder dysfunction. Coenzyme Q10 (CoQ10) is a pro-vitamin like substance that appears to be efficient for treatment of neurodegenerative disorders and ischemic heart disease. Our goal was to investigate the potential protective effect of CoQ10 in a rabbit model of in vivo bilateral ischemia and ischemia/reperfusion (I/R). MATERIAL AND METHODS: Six groups of four male New Zealand White rabbits each were treated with CoQ10 (3 mg/kg body weight/day-dissolved in peanut oil) (groups 1-3) or vehicle (peanut oil) (groups 4-6). Groups 1 and 4 (ischemia-alone groups) had clamped bilateral vesical arteries for 2 h; in groups 2 and 5 (I/R groups), bilateral ischemia was similarly induced and the rabbits were allowed to recover for 2 weeks. Groups 3 and 6 were controls (shams) and were exposed to sham surgery. The effects on contractile responses to various stimulations and biochemical studies such as citrate synthase (CS), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and catalase (CAT) were evaluated. The protein peroxidation indicator, carbonyl group, and nitrotyrosine contents were analyzed by Western blotting. RESULTS: Ischemia resulted in significant reductions in the contractile responses to all forms of stimulation in vehicle-fed rabbits, whereas there were no reductions in CoQ10-treated rabbits. Contractile responses were significantly reduced in vehicle-treated I/R groups, but significantly improved in CoQ10-treated rabbits. Protein carbonylation and nitration increased significantly in ischemia-alone and I/R bladders; CoQ10 treatment significantly attenuated protein carbonylation and nitration. CoQ10 up-regulated SOD and CAT activities in control animals; the few differences in CoQ10-treated animal in SOD and CAT after ischemia and in general increase CAT activities following I/R. CONCLUSIONS: CoQ10 supplementation provides bladder protection against I/R injury. This protection effect improves mitochondrial function during I/R by repleting mitochondrial CoQ10 stores and potentiating their antioxidant properties.
Asunto(s)
Antioxidantes/farmacología , Suplementos Dietéticos , Daño por Reperfusión/prevención & control , Ubiquinona/análogos & derivados , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Animales , Antioxidantes/administración & dosificación , Catalasa/metabolismo , Colina O-Acetiltransferasa/metabolismo , Citrato (si)-Sintasa/metabolismo , Masculino , Mitocondrias/metabolismo , Contracción Muscular/efectos de los fármacos , Conejos , Daño por Reperfusión/tratamiento farmacológico , Superóxido Dismutasa/metabolismo , Ubiquinona/administración & dosificación , Ubiquinona/farmacología , Ubiquinona/uso terapéutico , Vejiga Urinaria/metabolismoRESUMEN
Transurethral resection of the prostate (TURP) is the most common surgical procedure for relieving symptoms of benign prostatic hyperplasia. Here, we report our experience of current indications for TURP and their associated outcomes at Kaohsiung Medical University Hospital (KMUH). A total of 111 patients who underwent TURP at KMUH between May 2000 and December 2001 were included in this retrospective review. For each patient, the surgical indication was categorized into acute urinary retention, chronic complications (including renal impairment, recurrent urinary infection, bladder stone/diverticulum, post-void residue, and recurrent hematuria), and symptomatic prostatism. Thirty-five patients (31%) had acute urinary retention, 28 (27%) had chronic complications, and 48 (42%) had symptomatic prostatism. Most patients chose TURP only when medical treatment had failed to relieve symptoms, no matter what category they belonged to. Patients with acute urinary retention and chronic complications had larger prostates (p = 0.002) and more tissue resected (p = 0.05) than those with symptomatic prostatism. Patients with acute urinary retention seemed to be at greater risk of postoperative complications such as recurrent urinary retention and urinary tract infection. We suggest that urodynamic study may be necessary to rule out concomitant bladder dysfunction before surgery and that adequate prophylactic antibiotic treatment be used to decrease the risk of urinary tract infection during or after TURP, especially when pyuria is noted preoperatively in patients with acute urinary retention.
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Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Anciano , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resección Transuretral de la Próstata/efectos adversos , UrodinámicaRESUMEN
The first Conference on Asian Trends in Prostate Cancer Hormone Therapy was held in September 2001 to serve as a forum for Asian urologists to compare data on prostate cancer and discuss issues regarding the use of hormone therapy. The conference revealed that due to various cultural and philosophical factors, differences exist in prostate cancer management among the Asian countries. In addition, a lack of databases on hormone therapy was exposed in some countries. It was noted that many decisions in the treatment of prostate cancer are influenced by the strategies adopted in Western countries, and that attempts to formulate uniform guidelines for the Asian region have hitherto been unsuccessful. The main findings of the conference are reported in this review.