Cellular uptake of rose bengal is mediated by OATP1B1/1B3 transporters.

Due to its fluorescent properties and high yield of singlet oxygen, rose bengal (RB) is one of the most promising photosensitizers for cancer treatment. However, the negative charge of RB molecule may significantly hamper its intracellular delivery by passive diffusion through the cell membrane. Thus, specific membrane protein transporters may be needed. The organic anion transporting polypeptides (OATPs) are a well-characterized group of membrane protein transporters, responsible for cellular uptake of a number of drugs. To our knowledge, this is the first study that evaluates cellular transport of RB mediated by the OATP transporter family. First, electrified liquid-liquid interface, together with biophysical analysis and molecular dynamics simulations were used to characterize the interaction of RB with several models of a cellular membranes. These experiments proved that RB interacts only with the membrane's surface, without spontaneously crossing the lipid bilayer. Evaluation of intracellular uptake of RB by flow cytometry and confocal microscopy showed significant differences in uptake between liver and intestinal cell line models differing in expression of OATP transporters. The use of specific pharmacological inhibitors of OATPs, together with Western blotting and in silico analysis, indicated that OATPs are crucial for cellular uptake of RB.

A survey of methods for the evaluation of tissue engineering scaffold permeability.

The performance of porous scaffolds for tissue engineering (TE) applications is evaluated, in general, in terms of porosity, pore size and distribution, and pore tortuosity. These descriptors are often confounding when they are applied to characterize transport phenomena within porous scaffolds. On the contrary, permeability is a more effective parameter in (1) estimating mass and species transport through the scaffold and (2) describing its topological features, thus allowing a better evaluation of the overall scaffold performance. However, the evaluation of TE scaffold permeability suffers of a lack of uniformity and standards in measurement and testing procedures which makes the comparison of results obtained in different laboratories unfeasible. In this review paper we summarize the most important features influencing TE scaffold permeability, linking them to the theoretical background. An overview of methods applied for TE scaffold permeability evaluation is given, presenting experimental test benches and computational methods applied (1) to integrate experimental measurements and (2) to support the TE scaffold design process. Both experimental and computational limitations in the permeability evaluation process are also discussed.

On the use of in vivo measured flow rates as boundary conditions for image-based hemodynamic models of the human aorta: implications for indicators of abnormal flow.

The purpose of this study is to investigate how the imposition of personalized, non-invasively measured blood flow rates as boundary conditions (BCs) influences image-based computational hemodynamic studies in the human aorta. We extracted from 4D phase-contrast MRI acquisitions of a healthy human (1) the geometry of the thoracic aorta with supra-aortic arteries and (2) flow rate waveforms at all boundaries. Flow simulations were carried out, and the implications that the imposition of different BC schemes based on the measured flow rates have on wall shear stress (WSS)-based indicators of abnormal flow were analyzed. Our results show that both the flow rate repartition among the multiple outlets of the aorta and the distribution and magnitude of the WSS-based indicators are strongly influenced by the adopted BC strategy. Keeping as reference hemodynamic model the one where the applied BC scheme allowed to obtain a satisfactory agreement between the computed and the measured flow rate waveforms, differences in WSS-based indicators up to 49% were observed when the other BC strategies were applied. In conclusion, we demonstrate that in subject-specific computational hemodynamics models of the human aorta the imposition of BC settings based on non-invasively measured flow rate waveforms influences indicators of abnormal flow to a large extent. Hence, a BCs set-up assuring realistic, subject-specific instantaneous flow rate distribution must be applied when BCs such as flow rates are prescribed.

[Mycobacteria in swimming pool water and the meaning of microbiological conventional indicators]. / Presenza di micobatteri in acque di balneazione e predittività degli indicatori microbiologici convenzionali di qualità igienico sanitaria.

Monitoring program of hygienic quality water in twelve public swimming pools was performed. Legally required microbiological indicator parameters of safety for gastrointestinal illness were measured besides the analyses of Pseudomonas spp. and Staphylococcus spp. prevalence, frequency of recovery and number of nontuberculous mycobacteria. We detected positive samples for coliforms at lower rate (29.3%) than Pseudomonas (75.5%), Staphylococcus spp. (46%) and Mycobacteria (59.4%). We pointed out statistically significant correlation (r=0.67 p=0.0001) between Mycobacteria and Pseudomonas so we think that the latter might be a good predictive marker. As 82% of samples had free chlorine residual within the limits stated by Italian Laws, the efficacy of chlorination to prevent risk of infectious diseases transmission by route other than gastroenteric was discussed. A revision of both the sanitary significance of conventional microbial parameters and the related regulations appears necessary.

A multivariate analysis of lower urinary tract ageing and urinary symptoms: the role of fibrosis.

An investigative trial including 72 patients who underwent open surgery for benign prostatic hypertrophy (BPH) induced urinary symptoms was carried out with the purpose to obtain a deeper insight in the pathophysiology of this clinical picture. Prostate weight, stroma to parenchyma ratio, bladder wall fibrosis, I-PSS score, residual urine and uroflow obtained from these patients were processed by statistical multivariate analysis. The results point out the pivotal impact of prostate and bladder wall fibrosis in conditioning biological and chronological ageing of the lower urinary tract and relative symptoms.

Preliminary reports on morphological and ultrastructural changes in the corpora cavernosa of the rat after chronic arterial obstruction.

OBJECTIVES: Various authors have investigated the pathological findings of penile tissue after chronic arterial obstruction, but the significance of these changes in the corpora cavernosa remains unclear. In order to evaluate the possible damages in the erectile tissue after chronic arterial obstruction at different levels, we utilized an experimental model in rats to determine the changes in smooth muscle cells and elastic fibers of the erectile tissue by microscopic immunohistochemical and ultrastructural studies. METHODS: Twelve adult male Wistar rats were employed in this study. Ten were used for the experiments and two as control. The rats were anaesthetized with ether and intraperitoneal 10% chloral hydrate. Microsurgical isolation of the involved vessels was performed with the aid of a Zeiss dissecting microscope. Partial stenosis was achieved with 11/0 nylon and amputation of the penis was performed at previously established time periods. The partial stenosis was carried out at the level of the aortic below the renal vessels (Group A), the common iliac artery on both sides (Group B) and the hypogastric artery on the left side (Group C). Arterial obstruction was maintained in each group for 50, 40 and 25 days, respectively. RESULTS/CONCLUSIONS: In comparison with normal controls, the histological findings revealed discrete and diffuse interstitial hyalinosis with reducted elastic fibers, while dilated vascular lacunae were also present on TEM (Transmission Electron Microscope) and SEM (Scanning Electron Microscope) examination. The greatest ultrastructural damages were observed in the group with obstruction of the common iliac artery on both sides. The foregoing confirms that an eventual chronic obstruction of these arteries does not allow the formation of collateral vessels for the corpora cavernosa.

[BCG vs. BCG plus recombinant alpha-interferon 2b in superficial tumors of the bladder]. / BCG vs. BCG plus alpha-interferon 2b ricombinante nei tumori superficiali della vescica.

BCG intravesical instillation is a well established therapy for superficial bladder carcinoma as adjuvant and/or prophylactic treatment. However side-effects are frequent when full doses are employed and therefore low dose alternative schedules were proposed. Interferon intraluminal therapy for bladder TCC has been used with similar indication but the results did not encourage further single drug trials. A double arm random study, BCG full dose vs. BCG low dose, is presented. The results point out that the combination treatment is superior to BCG full dose therapy in terms of side effects and similar to BCG full dose as regards efficiency (5/18 vs 4/18 recurrences) after a follow-up of 24.11 +/- 8.15 for BCG and 16.72 +/- 8.7 for BCG + IFN.

[Single-blind study of the effect of doxazosin mesylate in benign prostatic hypertrophy]. / Etude en simple aveugle de l'efficacité du Mesylate de Doxazosin dans l'hypertrophie bénigne de prostate.

The purpose of this single blind study was to verify the efficiency of Doxazosin Mesylate, an alpha-1 adrenergic blocker, in patients with benign prostatic hyperplasia (BPH). This study involved 20 patients non placebo responders. The duration of treatment was 45 days with administration of Doxazosin Mesylate increased every 15 days from 1 to 2 mg and from 2 to 4 mg respectively. At the end of each dosage cycle the following investigations were performed: a) peak urinary flow, b) residual urinary volume, c) funneling of the prostatic urethra by means of permictional transrectal echography, d) Boyarsky's score. The analysis of these data, applying a two way analysis of variance (ANOVA), showed that Doxazosin Mesylate resulted in improvements in both urodynamic and symptomatic parameters. The statistical analysis proved also that there was a good correlation between the dosage of the drug up until 2 mg and the results from each parameter considered.

[Urologic applications of intralaparoscopic echography]. / Applicazioni urologiche dell'ecografia intralaparoscopica.

The impossibility to palpate organs and tissues is probably the most important drawback of the laparoscopic approach: laparoscopic sonography represent the only real alternative to manual palpation. The laparoscopic approach in the field of urology was initially limited to the identification of the undescended testes in paediatric urology and to the laparoscopic ligation of varicocele. More recently, it took into account the pelvic lymphadenectomy for staging prostatic and bladder cancer. The upper urinary tract and the retroperitoneum were approached more recently. In a preliminary phase the indications for laparoscopic nephrectomy were limited to benign diseases, such as atrophic kidney in patients with renal hypertension, and scarred pyelonephritic kidney. At present some preliminary experiences are reported about nephrectomy performed for carcinoma of the urether or of the upper collecting system and for renal masses of unknown origin. Another indication for a laparoscopic approach to the kidney is represented by symptomatic renal cysts. These cysts have been usually treated with percutaneous aspiration and/or sclerosis, but a high rate of recurrence is reported. Laparoscopy may be used to approach renal cysts with the advantage that most of the cystic wall could be excised, reducing the change of recurrence. Another possible indication for laparoscopy and laparoscopic sonography is the retroperitoneal lymphadenectomy in testes cancer with staging or therapeutic purposes. Nowadays preliminary experiences in laparoscopic adrenalectomy have been reported in a limited series of cases. In this report the Authors present their initial experience using a 7.5 MHz rigid probe having 400 crystal which can be inserted into a 10 mm trocar.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of echography in the diagnostic-therapeutic management of renal cysts]. / Ruolo dell'ecografia nell'iter diagnostico-terapeutico delle cisti renali.

Herein we report on the results of 171 out of 214 patients with renal cysts. In 127 cases diameter of cyst being less than < 6 cm, was monitored repeating renal ultrasound every 6 months: 78 patients underwent pecutaneous cyst echoguided puncture, while 9 patients were treated as follows: 4 by open surgery, 3 by laparoscopy and 2 by percutaneous treatment in general anaesthesia. Cysts are classified in 4 types and therapy is different according to Bosniak's classification. When the cyst is less than 6 cm in diameter and symptomatology is absent, we follow the patients up with yearly ultrasound. In our experience cyst sclerotization is carried out by injecting either ethanol or Trombovar or 50% glucose in water alone or associated with 2% Aethoxysclerol. The best results are obtained from the use of ethanol (30% of the volume of cyst). However some relapses are encountered after this kind of procedure. In these cases it is helpful to examine the cystic wall because of the presence of intracystic septa. Percutaneous treatment by means nephroscopy permits to visualize the cystic wall but it is not able to perform a biopsy of its wall. Laparoscopic treatment is performed by inserting 5 trocars with the patient under general anaesthesia. This technique is able to localize and biopsy the cystic wall without causing side-effects or complications. Open surgery was performed only in 4 patients affected with hidatid cyst. At present echoguided cyst puncture permits to approach the renal not complicated cysts, while laparoscopy constitutes a safe treatment in the case of benign recurrent and complicated cysts.(ABSTRACT TRUNCATED AT 250 WORDS)

[The role of echography in the intraoperative study of non-palpable testicular masses]. / Ruolo dell' ecografia nello studio intraoperatorio delle masse testicolari non palpabili.

Intraoperative ultrasound localization of the non palpable testicular lesions allows to detect small gonadal tumors or to well study benign testicular masses. Several methods have been proposed to study non palpable testicular masses including CT and NMR. Prospective studies of the efficacy of CT vs spermatic venography in localization of cryptorchid testes have also been reported: spermatic venography proved to be the most accurate of the two modalities even if possible neoplastic degeneration of testicular tissue is very difficult to investigate with this method. Herein we describe our clinical experience and particularly four cases in which we adopted intraoperative ultrasonography of testes with different results. M.S. a 28 year old infertile patient underwent testicular ultrasound during a check-up and a little image localized at the level of right testis was found. Even if no mass was palpable we decided to operate on the patient; an intraoperative testicular ultrasound revealed the precise localization so that the little mass was excised and examined at once. Histologic study confirmed the presence of tumoral tissue and orchiectomy was performed: deeper hystological studies confirmed it was a leydigioma. D.C. 27 year old bilaterally cryptorchid patient had been already operated on twice but no testicular structure was encountered at the level of inguinal channels. Neither preoperative abdominal ultrasound nor CT revealed the presence of the testes. At abdominal exploration both testes were localized in the iliac region. Intraoperative testicular ultrasound allowed us to localize a right testicular tumor: right orchiectomy and left autotransplantation were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Echo-flowmetric control 6 years after percutaneous treatment of varicocele]. / Controllo eco-flussimetrico a 6 anni di distanza dal trattamento percutaneo del varicocele.

Several Authors have discussed the long term efficacy of sclerotherapy; somebody supposes that percutaneous angiographic treatment of spermatic vein is not sure at all because the occlusion due to the sclerosing agents is not retained as long lasting. Studies have been done by other Authors about comparison of recurrent varicocele anatomy following surgery and percutaneous balloon occlusion: it is concluded that venous collaterals are identified easily by renal venography, and knowledge of these collaterals is helpful in planning further radiological treatment. Since 1980 we have always treated left varicocele by means of percutaneous sclerotherapy of the spermatic veins following renal phlebography: the treatment is done on an outpatient basis, in local anaesthesia. Sclerosing agents we usually adopt are: sodium-tetradecyl sulphate and alcohol. At our knowledge long-term results of this treatment have never been published; this is the reason for which long-term follow-up of 27 patients that 6 years ago underwent percutaneous sclerotherapy was done. Only 16 of them have accepted to repeat: a) physical examination; b) Doppler flowmetry; c) scrotal ultrasound. The presence of a varicocele was demonstrated in 2 out of 16 patients (12.5% of the case). These data confirms that percutaneous treatment performed following the procedures we adopted in 1986 has a long term efficacy in 87.5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Echo-guided puncture of intraprostatic cysts]. / Puntura ecoguidata di cisti intraprostatiche.

The occurrence of an obstruction of the ejaculatory ducts, in spite of its rarity, must be considered by the Urologists in the screening of the etiologic causes of obstructive azoospermia. Nowadays, the diagnostic approach, which includes the biochemical study of seminal plasma and prostatic ultrasound, often leads to the preoperative recognition of the site of obstruction. Various surgical and endoscopic techniques have been adopted for the treatment of ejaculatory duct obstructions in different historical periods. Herein we describe our experience that starts from 1979. 17 infertile patients with intraprostatic cysts and 2 with a stenosis of the veru montanum were treated by us following these criteria: 9 azoospermic patients underwent scrototomy and endoscopy; 10 patients with a severe oligozoospermia underwent echo-guided puncture of an intraprostatic cyst. The patients were placed in the lithotomy position, a 16 G needle was adopted and by means ultrasound was possible to follow the needle entering the cyst. When no spermatozoa was detected in the cystic liquid, sclerosing agents (Sodium-tetradecyl-sulphate 30 mg in 1 l.) was introduced. This easy procedure was carried out on outpatients in local anaesthesia. One out of ten oligozoospermic patients had to repeat the echo-guided puncture of intraprostatic cyst as the first attempt had been followed by recurrence. Eight out of ten subfertile patients who had undergone percutaneous echo-guided treatment had longer than 1 year follow-up: in seven cases an increase in sperms number and motility was obtained; in one case sperm count remained unmodified. In three cases the partners became pregnant.

[Bulbocavernosus reflex and somatosensory evoked potential of the pudendal nerve in diabetic impotence]. / El reflejo bulbocavernoso y el potencial evocado somatosensorial (SEP) del nervio pudendo en la impotencia diabética.

The present study investigated the sensitivity of the bulvocavernosus reflex (BCR) and the somatosensory evoked potential (SEP) of the pudendal nerve in neurogenic impotence, the study comprised 22 males with diabetes type II. Of these, 11 had neurogenic impotence. The SEP was found to be normal in all cases, whereas BCR changes were observed in 36.4% of the patients who were not impotent and in 63.6% of the impotent males. This difference, however, is not statistically significant. The results show that in diabetic pelvic neuropathy compromise of the vegetative fibers does not necessarily mean injury to the somatic.

[Bilateral abdominal testicles in the adult. Microsurgical and laparoscopic therapy]. / Testicoli addominali bilaterali nell'adulto. Terapia microchirurgica e laparoscopica.

B. L. a 27 year old bilaterally cryptorchid patient underwent right testicular autotransplantation in the presence of a quite normal testis. After one year the patency of microsurgical anastomosis was confirmed by means of Doppler flowmetry and scrotal echography demonstrated the presence in the scrotum of a testis provided will normal echogenicity. Left laparoscopic orchiectomy was planned. A small semilunar skin incision was made just below the rim of the umbilicus. Veress needle was introduced: as soon as the needle pierced the parietal peritoneum, its spring mechanism was released allowing the sharp needle point to retract leaving only the blunt tip protruding. Carbon dioxide gas was insufflated through the side part of the Veress needle until adequate abdominal distension was achieved. After having removed the Veress needle, the laparoscope on its sharp-pointed trocar was introduced into the peritoneal cavity and left testis was easily localized. Four trocars were introduced up to proceed to laparoscopic orchiectomy. The patient was discharged two days after. In our opinion in the presence of a bilateral cryptorchism in the adult, is better to plan a monolateral autotransplantation. After having verified the long-term result of microsurgery we can decide if a contralateral orchiectomy has to be planned.

[Impotence: introductory notes]. / Le impotenze: note introduttive.

If we define erectile impotence as the inability to achieve and maintain a firm erection we can distinguish several pathogens of impotence: psychologic disorders, neurogenic sinusoidal disorders, arterial disorders, venous & sinusoidal disorders and systemic diseases and other disorders can cause erectile impotence. An etiologic screening of impotence must be carried out by Urologists in order to adopt the best surgical approach. Especially when surgery has to be planned, a complete, often invasive screening associated with a super-specialist diagnostic study is necessary at the beginning of any procedure. Different approaches to impotence can be adopted on the basis of patient's age, etiology and failure of other devices. The main methods of surgical correction of impotence may be divided as follows: a) percutaneous transluminal angioplasty (P.T.A.); b) revascularization; c) surgical treatment of "venous leakage", d) trans-luminal veno-occlusion (T.L.V.O.); e) correction of penile curvature; f) prostheses placement. The diagnosis of arteriogenic impotence depends upon the arteriographic demonstration of bilateral hemodynamically significant obstruction. In our experience the injection of papaverine during the test has provided a better visualization of cavernous arteries and helicine branches. Reduction of luminal diameter by more than 50% suggest a hemodynamically significant stenosis. Intracavernous injection of vasoactive agents has provided an attractive alternative to surgery. We have employed papaverine alone or with phentolamine or phenoxybenzamine. After short term treatment, some patients have achieved good erections without further injections. For P.T.A. of the distal internal pudendal arteries our approach has been via the ipsilateral or contralateral femoral arteries. Under local anesthesia a penile arteriographic catheter is placed in the internal pudendal artery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of penile ultrasonography in erection deficit]. / Ruolo dell'ecotomografia peniena nei deficit d'erezione.

The presence of penile nodule, curvature, disorders in blood flow to and from the corpora cavernosa is often correlated with organic sexual impotence. Echography allows to obtain a clear imaging of penile structures: diameters of corpora cavernosa can be measured before and after injection of vasoactive drugs. In our study penile structure were evaluated using a Combison 310 and a Toshiba with 7.5 MHz probe. In a lot of cases echography was repeated after intracavernous injection of PGE 1 or papaverine. The equipment needed for this evaluation is expensive but echography is undoubtedly less invasive than other equivalent examinations like cavernosography. Although the sensitivity and specificity of penile echography have not yet been clearly established this test is generally considered to be an useful and objective one. Penile echography is particularly usefull in discriminating between echogenic and not-echogenic nodules in case of Peyronie disease.

[Testicular autotransplant and laparoscopic orchiectomy in a case of bilateral adult cryptorchism]. / Autotrapianto testicolare ed orchiectomia laparoscopica in un caso di criptorchidismo bilaterale dell'adulto.

B.L. a 27 year old bilaterally cryptorchid patient underwent right testicular autotransplantation in the presence of a quite normal testis. After one year the patency of microsurgical anastomosis was confirmed by means Doppler flowmetry and scrotal echography demonstrated the presence into the scrotum of a testis provided of a normal echogenicity. Left laparoscopic orchiectomy was planned. A small semilunar skin incision was made just below the rime of the umbilicus. Veress needle was introduced: as soon as the needle pierced the parietal peritoneum, its spring mechanism was released allowing the sharp needle point to retract leaving only the blunt tip protruding. Carbon dioxide gas was insufflated through the side part of the Veress needle until adequate abdominal distension was achieved. After having removed the Veress needle, the laparoscope on its sharp-pointed trocar was introduced into the peritoneal cavity and left testis was easily localized. Four trocars were introduced up to proceed to laparoscopic orchiectomy. The patient was discharged two days after. In our opinion in the presence of a bilateral cryptorchism in the adult, is better to plan a monolateral autotransplantation. After having verified the long-term result of microsurgery we can decide if a contralateral orchiectomy has to be planned.