Purpose: To establish whether the citrate concentration in the seminal fl uid ([CI-TRATE]) measured by means of high-resolution nuclear magnetic resonance spectroscopy (1HNMRS) is superior to the serum prostate-specifi c antigen (PSA) concentration in detecting of clinically signifi cant prostate cancer (csPCa) in men with persistently elevated PSA. Materials and Methods: The group of patients consisted of 31 consecutively seen men with histological diagnosis of clinically localized csPCa. The control group consisted of 28 men under long-term follow-up (mean of 8.7 ± 3.0 years) for benign prostate hyperplasia (BPH), with persistently elevated PSA (above 4 ng/mL) and several prostate biopsies negative for cancer (mean of 2.7 ± 1.3 biopsies per control). Samples of blood and seminal fl uid (by masturbation) for measurement of PSA and citrate concentration, respectively, were collected from patients and controls. Citrate concentration in the seminal fl uid ([CITRATE]) was determined by means of 1HNMRS. The capacities of PSA and [CITRATE] to predict csPCa were compared by means of univariate analysis and receiver operating characteristic (ROC) curves. Results: Median [CITRATE] was signifi cantly lower among patients with csPCa compared to controls (3.93 mM/l vs. 15.53 mM/l). There was no signifi cant difference in mean PSA between patients and controls (9.42 ng/mL vs. 8.57 ng/mL). The accuracy of [CITRATE] for detecting csPCa was signifi cantly superior compared to PSA (74.8% vs. 54.8%). Conclusion: Measurement of [CITRATE] by means of 1HNMRS is superior to PSA for early detection of csPCa in men with elevated PSA.
Patients with SCI have a significant reduction of seminal citrate as a consequence of neurological dysfunction of the prostate.
Acrocomia totai Mart (Arecaceae) is a palm tree native to South America, widely studied for biodiesel production. The aim of this work was to perform the first phytochemical study of A. totai leaves, as well as to do biological assays against human cancer cell lines. A new triterpene of the hopane class named totaiol (1), three known triterpenes (2-4), and two phytosteroids (5-6) were identified. The new natural product was characterized using 1D and 2D NMR, single crystal X-ray diffraction analises, high resolution mass spectrometry. The intercontacts in the crystal packing were also analised. Complete stereochemical characterization of compound 1 revealed an unusual positioning pattern for methyl and isopropenyl groups in the polycyclic skeleton.Compounds 1-5 were evaluated for the first time in antiproliferative assays against Ca Ski, MCF-7 and MCF-10 cells. The new natural product was active against Ca Ski cells with IC 50 ≤ 6.25 µg mL -1 .
model. We investigated whether intrathecal (i.t.) ALX-1393 can inhibit the autonomic response during bladder HD in the IC/BPS rat model. METHODS: Animals Twelve Sprague-Dawley female white rats (200-250g) were divided into 2 groups (control, n¼12 and ALX-1393, n¼12, respectively). All rats received protamine sulfate (PS) 10mg/ml in the urinary bladder for 30 minutes followed by 750ug/ml lipopolysaccharide (LPS) instillation for 45 minutes. One week after the instillation, cystometry (n¼6, in both groups, respepctively) and HD (n¼6, in both groups) was performed.Hydrodistention and Cystometry Based on previous experiments, HD was performed at a pressure of 150-170 mmHg for 30 seconds with a 3 minute interval. Autonomic response was quantified as the difference of mean arterial pressure between baseline period prior to distension and during HD. Anesthesia was performed with Intraperitoneal injection of Zoletil (Tiletamine+Zolazepam) 0.1cc/100g and Rompun (Xylazine) 0.025~0.04/100g. After placing a PE-50 tubing into the bladder, awake cystometry was performed by infusing physiological saline at a slow infusion rate (0.04ml/min).Intrathecal administration of ALX-1393 Through the subarachnoid space, a polyethylene catheter was advanced and placed at L6-S1 spinal cord level. Saline (for control) or ALX-1393 was injected after 1st HD, and 2 more sessions were performed 5 and 30 minutes after saline or ALX-1393 injection.RESULTS: A significant increase in BP was consistently observed for 3 consecutive sessions of HD in control group (19.49AE5.50, 13.63AE6.22 and 17.18AE7.67mmH2O). In ALX-1393 group, minimal change of BP was observed during HD which was performed 5 minutes after ALX-1393 i.t. injection (4.22AE9.69mmH2O). The exaggerated autonomic response was observed 30 minutes after ALX-1393 i.t. injection (15.62AE8.60mmH2O). On cystometry, intercontraction interval (ICI) in control group demonstrated little change after saline i.t injection (12.17AE20.58, p¼0.207), while significantly prolonged ICI was seen immediately after ALX-1393 i.t injection (57.83AE24.86, p¼0.005).CONCLUSIONS: ALX-1393 inhibits the exaggerated autonomic responses during bladder HD and ameliorates detrusor overactivity in the IC/BPS rat model. These findings suggest that GlyT2 may be a novel therapeutic target for the treatment of IC/BPS.
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