The prostate-specific membrane antigen (PSMA) is a transmembrane protein, that is highly expressed on the surface of prostate cancer cells. In the last few years, several PSMA-specific ligands have ...been developed, that can be successfully used to detect primary prostate cancer, tumor recurrences and metastases as well.
The goal of our work was to examine the clinical application of a
technetium-labeled PSMA-radiopharmaceutical as part of the routine diagnostics of prostate cancer.
We examined 15 male patients with verified prostate adenocarcinoma with suspicion of progression or recurrence of the disease. We performed whole-body PSMA-SPECT/CTs and multiparametric MRIs of the prostate and the pelvic regions within a week. We used
Tc-mas3-y-nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were visually evaluated by independent observers. The results were compared with the follow-up bone scintigraphies as well.
Twenty-two PSMA-positive lesions were found. Nine of them were localized outside, 13 were within the MRI's field of view. From these 13 lesions, 7 matched with the SPECT/CT results and in 5 cases the MRI images showed no abnormalities. In one case, bone metastasis was suspected on the MRI scan but there was no corresponding pathological tracer uptake on the SPECT images. In two patients, none of the examinations showed signs of prostate malignancy. Four patients had PSMA-positive bone metastases. One of them had a matching PSMA/SPECT and bone scintigraphy result and in one case the PSMA examination showed metastasis in contrast to the negative bone scintigraphy.
PSMA-SPECT/CT with
Tc-mas3-y-nal-k(Sub-KuE) is a promising diagnostic tool. This technique is capable of visualizing bone metastases and it can detect local recurrences and visceral metastases as well. Orv Hetil. 2018; 159(35): 1433-1440.
Large-conductance Ca(2+) -activated K(+) channels (BKC a ), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening ...of BKC a channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is little information on the role of BKC a channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of BKC a channels in endothelium-dependent and endothelium-independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change in isometric force was recorded in microvascular myographs, and endothelium-dependent nitric oxide (NO) and endothelium-derived hyperpolarization (EDH)-type and endothelium-independent (NO-donor) relaxations were measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked NO- and EDH-type relaxations, which were sensitive to iberiotoxin (IbTX), a selective blocker of BKC a channels. Iberiotoxin also inhibited relaxations induced by a NO-donor, sodium nitroprusside. NS11021, a selective opener of BKC a channels, evoked pronounced relaxations that were inhibited in the presence of IbTX. NS13558, a BKC a -inactive analogue of NS11021, failed to relax human penile small arteries. Our results show that BKC a channels are involved in both NO- and EDH-type relaxation of intracavernous penile arteries obtained from healthy men. The effect of a selective opener of BKC a channels also suggests that direct activation of the channel may be an advantageous approach for treatment of impaired endothelium-dependent relaxation often associated with erectile dysfunction.
Abstract
Large‐conductance
C
a
2+
‐activated
K
+
channels (
BK
C
a
), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, ...opening of
BK
C
a
channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is little information on the role of
BK
C
a
channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of
BK
C
a
channels in endothelium‐dependent and endothelium‐independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change in isometric force was recorded in microvascular myographs, and endothelium‐dependent nitric oxide (
NO
) and endothelium‐derived hyperpolarization (
EDH
)‐type and endothelium‐independent (
NO
‐donor) relaxations were measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked
NO
‐ and
EDH
‐type relaxations, which were sensitive to iberiotoxin (IbTX), a selective blocker of
BK
C
a
channels. Iberiotoxin also inhibited relaxations induced by a
NO
‐donor, sodium nitroprusside.
NS
11021, a selective opener of
BK
C
a
channels, evoked pronounced relaxations that were inhibited in the presence of IbTX.
NS
13558, a
BK
C
a
‐inactive analogue of
NS
11021, failed to relax human penile small arteries. Our results show that
BK
C
a
channels are involved in both
NO
‐ and
EDH
‐type relaxation of intracavernous penile arteries obtained from healthy men. The effect of a selective opener of
BK
C
a
channels also suggests that direct activation of the channel may be an advantageous approach for treatment of impaired endothelium‐dependent relaxation often associated with erectile dysfunction.
Chronic over distention may lead to enterocystoplasty rupture. It is hypothesized that pressure induced microvascular derangement and subsequent ischemia of the enterocystoplasty intestinal patch may ...have a role in this process. We describe distention induced microcirculatory alterations in a chronic rat model of enterocystoplasty using intravital video microscopy.
Microcirculation in the muscle layer of the intact bladder and intestine, and in the enterocystoplasty 90 days after surgery were examined at greater and less than urethral sphincter closure pressure. Microcirculatory changes were recorded during stepwise increments of intraluminal pressure up to 80 mm. Hg or when 20 mm. Hg was continuously maintained for 60 minutes.
The enterocystoplasty components of intestine and bladder displayed baseline microcirculatory characteristics similar to those observed in the intact organs. As evidenced by microcirculatory flow and functional capillary density measurements in the intact intestine and the ileal portion of enterocystoplasty, intraluminal pressure elevation to greater than 25 or 30 mm. Hg significantly compromised capillary perfusion by approximately 50% and 75%, respectively. Lower intraluminal pressure did not cause microcirculatory disturbance even when maintained for a longer period. In the intact bladder and bladder portion of enterocystoplasty only pressure increases to greater than 80 mm. Hg affected tissue perfusion.
Intravital microscopy in the augmented rat bladder is a sensitive and suitable means of assessing clinically relevant microcirculatory changes. These experiments demonstrate the significance of distention induced microcirculatory impairment in the intact bowel and the intestinal site of enterocystoplasty even at less than urethral closure pressure.
The main goals of our studies were 1. to develop a standardized experimental model for the observation of the microcirculatoiy characteristics of the urinary bladder and 2. to investigate the ...mechanism of microcirculatory dysfunction of the bladder under acute and chronic pathological conditions. In the first part, the microcirculatory consequences of ischemia-reperfusion (I/R) and the roles of the endogenous endothelin-1 (ET-1) were evaluated using selective endothelin receptor antagonist treatment and intravital videomicroscopy (IVM) techniques. Secondly, the effects of elevated intravesical pressure were observed in a chronic rat model of enterocystoplasty (ECP) using a de-tubularised ileal segment for the augmentation of the urinary bladder.In the acute studies, the consequences of 60 min ischemia followed by 30 min reperfusion were studied in a rat model. I/R of the bladder was elicited by clamping and releasing of the cystic arteries. The role of the ET-1 in this pathology was investigated with the administration of the selective endothelin-A receptor antagonist BQ 610 and the relevant microcirculatory parameters were evaluated using fluorescence IVM. Arteriolar and venular diameters, functional capillary density, venular red blood cell velocity, arteriolar and venular macromolecular leakage and leukocyte-endothelial cell interactions (rolling and adherent leukocytes) were assessed by a computer-assisted analysis system.After I/R a severe inflammatory reaction evolved and significant microcirculatory failure were observed in the urinary bladder. Pretreatment with BQ 610 effective by attenuated the effects of I/R-induced inflammation, and partially prevented the microcirculatory disturbances.In the chronic experiments with ECP the bladder was filled with a constant volume of saline solution to maintain the physiological intravesical pressure, or alternatively, the ECP also was cannulated and the intravesical pressure was elevated stepwise by 10 mmHg. The bladder or the ECP was positioned on a stage and fluorescence IVM measurements were performed during constant intravesical pressure or after each increment of pressure of the ECP.Filling the bladder with a constant volume of saline solution resulted in a physiological intravesical pressure and microcirculatory parameters or intravesical pressure did not change significantly during the 180-min observation period. Stepwise increases of the intravesical pressure did not significantly affect microcirculatory flow and functional capillary density of the bladder or the bladder part of ECP until the pressure reached 70 mmHg, and then significant microcirculatory disturbances were observed at higher pressure values. Microcirculation, however, was significantly diminished both in the intact bowel wall and in the intestinal graft part of the ECP at 25 mmHg intraluminal pressure. On the other hand, below this level (20 mmHg) no significant damage occurred in the microcirculation in both part of ECP even after a longer period.These results demonstrate the sensitivity of the microcirculation of the intestinal part of the ECP to clinically relevant pressure increases. This model can serve as a basis for further investigations to better understand the basic pathophysiology of the urinary bladder at the microcirculatory level.
Intravital fluorescence microscopy (IVM) is a widely used method to study the microcirculation in several organs. Our aim was to develop a standard rat model to evaluate the microcirculatory ...characteristics of the urinary bladder under physiological pressure conditions using the most advanced fluorescence videomicroscopic techniques. Spraque-Dawley rats were used after filling their bladders with a constant volume of saline solution. The intravesical pressure was continuously monitored. The bladder was positioned on a specially designed stage and IVM measurements were made at the beginning, the 90th, 120th and 180th min. Arteriolar and venular diameters, functional capillary density, venular red blood cell velocity, arteriolar and venular macromolecular leakage and leukocyte-endothelial cell interactions (observation of rolling and firmly adherent leukocytes) were quantitatively assessed by a computer assisted analysis system. Neither microcirculatory parameters nor the intravesical pressure changed significantly during the observation period of 180 min using constant filling volume. We successfully established a new, well functioning and reproducible model to study the microcirculation of the rat bladder using intravital fluorescent microscopy.
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