A comprehensive monitoring approach for a naturally anoxic aquifer beneath a controlled landfill.

The processes leading to high levels of arsenic (As), iron (Fe), and manganese (Mn) in groundwater, in a naturally reducing aquifer at a controlled municipal landfill site, are investigated. The challenge is to distinguish the natural water-rock interaction processes, that allow these substances to dissolve in groundwater, from direct pollution or enhanced dissolution of hydroxides as undesired consequences of the anthropic activities above. Ordinary groundwater monitoring of physical-chemical parameters and inorganic compounds (major and trace elements) was complemented by environmental isotopes of groundwater (tritium, deuterium, oxygen-18 and carbon-13) and dissolved gases (carbon-13 of methane and carbon dioxide and carbon-14 of methane). Pearson/Spearman correlation indices, as well as Principal Component Analysis (PCA), were used to determine the main correlations among variables. The concurrent presence of As, Fe and CH4, as reported in similar anoxic environments, suggests that anaerobic oxidation of methane could drive the reductive dissolution of As-rich Fe(III)(hydro)oxides. Manganese is more sensitive to carbon dioxide, possibly due to a decrease in pH which accelerates the dissolution of Mn-oxides. Finally, we found that tritium and deuterium, which have been used for decades as leachate tracer in groundwater, may be subject to false positives due to the reuse of water recovered from leachate treatment (which has the same isotopic signature of leachate) within the plants, to comply with the requirements of the circular economy. The integration of the environmental isotope analysis into the traditional monitoring approach can effectively support the comprehension of processes. However, this strategy needs to be complemented by a good conceptual hydrogeological model and expert evaluation to avoid misinterpretations.

Antarctic permafrost degassing in Taylor Valley by extensive soil gas investigation.

Ongoing studies conducted in northern polar regions reveal that permafrost stability plays a key role in the modern carbon cycle as it potentially stores considerable quantities of greenhouse gases. Rapid and recent warming of the Arctic permafrost is resulting in significant greenhouse gas emissions, both from physical and microbial processes. The potential impact of greenhouse gas release from the Antarctic region has not, to date, been investigated. In Antarctica, the McMurdo Dry Valleys comprise 10 % of the ice-free soil surface areas in Antarctica and like the northern polar regions are also warming albeit at a slower rate. The work presented herein examines a comprehensive sample suite of soil gas (e.g., CO2, CH4 and He) concentrations and CO2 flux measurements conducted in Taylor Valley during austral summer 2019/2020. Analytical results reveal the presence of significant concentrations of CO2, CH4 and He (up to 3.44 vol%, 18,447 ppmv and 6.49 ppmv, respectively) at the base of the active layer. When compared with the few previously obtained measurements, we observe increased CO2 flux rates (estimated CO2 emissions in the study area of 21.6 km2 ≈ 15 tons day-1). We suggest that the gas source is connected with the deep brines migrating from inland (potentially from beneath the Antarctic Ice Sheet) towards the coast beneath the permafrost layer. These data provide a baseline for future investigations aimed at monitoring the changing rate of greenhouse gas emissions from Antarctic permafrost, and the potential origin of gases, as the southern polar region warms.

Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Role of magnetic resonance spectroscopic imaging ([¹H]MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) in identifying prostate cancer foci in patients with negative biopsy and high levels of prostate-specific antigen (PSA).

PURPOSE: The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy. MATERIALS AND METHODS: This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies. RESULTS: After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma. CONCLUSIONS: The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.

Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences.

Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.

Prevalence of antibodies against Bubaline herpesvirus (BuHV-1) among Mediterranean water buffalo (Bubalus bubalis) with implications in buffalo trade.

BACKGROUND: Both Bovine herpesvirus (BoHV-1) and Bubaline herpesvirus (BuHV-1) have been reported to cross the species barrier. Antibody seroconversion in glycoprotein E (gE) blocking ELISA during BuHV-1 infection has been documented. Recent diagnostic efforts have focused on the development and application of discriminatory tests to distinguish between infections with BoHV-1 and BuHV-1. OBJECTIVE: To evaluate the impact and distribution of these two infections in water buffalo farms in two regions (Piedmont (n = 3) and Campania (n = 10), Italy) where infectious bovine rhinotracheitis control programs have been implemented. ANIMALS AND METHODS: Sampling was carried out on 13 buffalo farms comprising 1089 animals using specific gE-indirect ELISA's test able to discriminate among BoHV-1 and BuHV-1 infections. RESULTS: 59.0% of animals reacted positive to ELISA (irrespective of whether BoHV-1 or BuHV-1 antigen was used) and 86.4% of these were reactive to BuHV-1 only, whereas 11.8% showed absorbance values for both antigens and were classified as inconclusive. There was a statistically significant age-related difference in BuHV-1 infection rates but not in overall individual (47% vs. 58%) or herd prevalence (100% vs. 90%) of infection between the two regions. CONCLUSION: The low percentage of sera reactive to BoHV-1 (1.8%, 12/643) indicates that BuHV-1 may be the main circulating alphaherpesvirus infection in Mediterranean water buffalo in the two study areas. Since Bubalus bubalis is included in Directive 64/432/EEC on animal health problems affecting intra-community trade in bovine animals, diagnostic testing with nonspecific ELISA for BoHV-1 infection in buffalo may yield false-positive reactions. This scenario could lead to economic losses and hamper buffalo trade and movement, particularly for reproduction purposes.

Motion correction in MRI of the brain.

Subject motion in MRI is a relevant problem in the daily clinical routine as well as in scientific studies. Since the beginning of clinical use of MRI, many research groups have developed methods to suppress or correct motion artefacts. This review focuses on rigid body motion correction of head and brain MRI and its application in diagnosis and research. It explains the sources and types of motion and related artefacts, classifies and describes existing techniques for motion detection, compensation and correction and lists established and experimental approaches. Retrospective motion correction modifies the MR image data during the reconstruction, while prospective motion correction performs an adaptive update of the data acquisition. Differences, benefits and drawbacks of different motion correction methods are discussed.

Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura.

PURPOSE: To define response to therapy and ultimate outcome of adults with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: We retrospectively analyzed patients with ITP diagnosed between 1978 and 1988, and reexamined them between June 1992 and March 1993. Data from 208 cases were collected. Median patient age was 44 years (range 14 to 78) at the time of diagnosis, and 51 years (range 19 to 86) at reexamination. Length of follow-up ranged from 48 to 151 months (median 92) and was longer than 10 years in 26 patients (12.5%). Reexamination included a careful interview, physical examination, complete blood count, screening for HIV infection, determination of platelet-bound IgG, and, in persistently thrombocytopenic patients, autoimmunity markers and routine laboratory investigations. RESULTS: A total of 121 patients with fewer than 50 x 10(9) platelets per liter received an initial treatment with prednisone (PDN) at a dosage of 1 mg/kg of body weight for 1 month. Refractory or relapsed cases underwent splenectomy and/or other therapeutic modalities. In 87 patients with greater than 50 x 10(9) platelets per liter, no therapy was scheduled. An initial complete response to PDN was observed in 38.8% cases. A sustained complete remission (CR) lasting more than 6 months with no maintenance therapy was attained in 18.7%. At the time of last follow-up only 11 of these patients remained in CR. Sixty-three patients underwent splenectomy. Forty-seven (74.6%) had a CR, with 41 achieving a prolonged recovery (> 6 months). Twelve other cases attained a sustained partial remission. Long-lasting recoveries were observed in 7 other cases following alternative treatments. Spontaneous remissions occurred in 8 of 87 untreated cases after observation periods of 6 months or more. Eleven deaths were recorded (6 women and 5 men, median age 73), but only 5 were attributable to thrombocytopenia. At last control, 43 patients were in complete remission and free from therapy, and 52 were still on therapy. Four thrombocytopenic patients had laboratory features and a clinical history consistent with an autoimmune disease. CONCLUSIONS: This analysis of ITP in adults suggests that splenectomy remains the most effective treatment. The majority of patients who undergo splenectomy can have a CR for many years, while only a minority of those who do not have this therapeutic modality or fail it are likely to attain similar results. The long-term prognosis of ITP is benign even in refractory cases. Spontaneous remissions can be observed in a significant percentage of untreated patients (about 9%). The development of overt autoimmune diseases is relatively uncommon. Particular attention should be given to the management of ITP in the elderly, where bleeding episodes of the central nervous system tend to occur more frequently.

Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma.

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Left anterior descending coronary artery grafting via left anterior small thoracotomy without cardiopulmonary bypass.

BACKGROUND: We explored the possibility of anastomosing the left anterior internal mammary artery (LIMA) to the left anterior descending artery in a beating heart via a left anterior small thoracotomy. METHODS: This procedure was performed in 155 of 162 scheduled patients; in 7 (4.3%) the left anterior descending artery was not suitable or was too small. The chest was opened in the fourth intercostal space (mean wound length, 10.5 cm) and the LIMA was harvested for about 4 cm. The left anterior descending artery was occluded by means of two 4/0 Prolene (Ethicon, Somerville, NJ) sutures, and the proximal suture was snared. The anastomosis was performed with two 8/0 Prolene sutures while the heart was beating. Early postoperatively all patients underwent repeat angiography or a Doppler flow assessment of the LIMA or both. RESULTS: The LIMA was connected directly to the left anterior descending artery in 144 patients and with interposition of an inferior epigastric artery in 11. In 2 patients the diagonal branch was also grafted using an inferior epigastric artery from the LIMA. One patient (0.6%) died 38 days after the operation due to multiorgan failure. Nine patients (5.8%) had failure requiring a redo operation: 7 (4.5%) early and 2 (1.3%) late. One additional patient had a late percutaneous transluminal coronary angioplasty for anastomotic stenosis. At a mean 5.6 months of follow-up, 143 patients (92.2%) were alive, asymptomatic with or without medical treatment, and without cardiac events. CONCLUSIONS: Left internal mammary artery-to-left anterior descending artery anastomosis performed on a beating heart via a left anterior small thoracotomy is a safe procedure. In selected patients the operation has good early and midterm results.

Relation between ST segment elevation during dobutamine stress test and myocardial viability after a recent myocardial infarction.

OBJECTIVE: To assess the relation between ST segment elevation during the dobutamine stress test and late improvement of function after acute Q wave myocardial infarction. PATIENTS AND DESIGN: 70 patients were studied a mean (SD) 8 (3) days after acute myocardial infarction with high dose dobutamine-atropine stress echocardiography and a follow up echocardiogram at 85 (10) days. A score model based on 16 segments and four grades was used to assess left ventricular function. Functional improvement was defined as a reduction of wall motion score > or = 1 in > or = 1 segments at follow up. INTERVENTION: Myocardial revascularisation was performed in 23 patients (33%) before follow up studies. RESULTS: ST segment elevation occurred in 40 patients (57%). Late functional improvement occurred in 35 patients (50%). Functional improvement was more common in patients with ST segment elevation (68% v 30%, P < 0.005) and they had a higher mean (SD) number of improved segments at follow up (1.9 (2.2) v 0.5 (1.1), P < 0.005). The wall motion score index decreased between baseline and follow up in patients with ST segment elevation (1.54 (0.50) v 1.48 (0.43), P < 0.05) but not in patients without ST segment elevation (1.39 (0.60) v 1.45 (0.47)). The accuracy of ST segment elevation for the prediction of functional improvement was similar to that of low dose dobutamine echocardiography in patients with anterior infarction (80% v 83%) and in patients who underwent revascularisation (78% v 83% respectively). CONCLUSION: In patients with a recent Q wave myocardial infarction, dobutamine-induced ST segment elevation is a valuable marker of myocardial viability particularly when the test is performed without or with suboptimal echocardiographic imaging.

Safety profile of selective alpha-1 adrenoceptor antagonists in the treatment of benign prostatic hyperplasia.

Further identification of the alpha-1 adrenoceptor present in various tissues using pharmacological and molecular biological studies has revealed that there are three subtypes of the alpha-1 adrenoceptor. This raised the possibility that there could be one subset of alpha-1 adrenoceptors within the human prostate and these might differ from those in the vascular. Binding experiments defined the functionally important alpha-1 subtype in the human prostate. It has been postulated that a drug with relatively high affinity for the alpha-1 adrenoceptor may be "prostate-selective". Such a drug may be as effective as other alpha-1 adrenoceptor antagonists but may have less effect on blood pressure and cause fewer vasodilatory side effects. The safety profile of non-subtype selective and subtype selective long-acting alpha-1 blockers is considered. However, Quantitative analysis showed that the amount of alpha-1a receptor differs from biopsy to biopsy, suggesting that prostates will differ in their response to an alpha blocker even when it is alpha-1a selective. Polymerase chain reaction (PCR) technique can be used to determine quantitatively alpha-1a receptor in small amount of tissue; at present, however, no non invasive parameters have been tested.

Peptide growth factors: clinical and therapeutic strategies.

The literature contains many accounts of studies in which tumour growth has been accelerated by administration of a particular mitogen and the response then inhibited by co-administration of the corresponding antagonist. Much effort has been focused on the development of cytokine or growth factor antagonists. Like most other cancer therapies, biological therapies will undoubtedly have undesirable toxicities because the proteins they target may not be unique to malignant cells. We reviewed the clinical and therapeutic potential of growth factor agonists and antagonists in some non urologic and urologic diseases. In a recent report we demonstrated that both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor. Simultaneous treatment with 1 nM R1881 and 100 nM OH-Flutamide, completely counteracted the androgen-induced increase of Epidermal Growth Factor (EGF) levels. Moreover we found that Testosterone, DHT and EGF are mainly concentrated in the periurethral zone in human BPH and long term treatment with Finasteride and with Flutamide modify the distribution and concentration of these factors. Some authors analyzed whether and addition of aurin tricarboxylic acid (ATA) can reduce the growth rate of basic FGF-dependent cells in a manner similar to suramin.

New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.

Three new different aspects of prostate cancer have been considered in this review: the existence of an hereditary form, the role of estrogens as predisposing factors and the efficacy of differentiation therapies. Prostate cancer shows a stronger familial aggregation than colon and breast carcinoma. Hereditary prostate cancer is distinguished by early age at onset and autosomal dominant inheritance within families. However, only 2% of all prostate cancer in United States white men occur in those 55 years old or younger. Thus, the impact of hereditary prostate cancer in the population is the greatest at younger ages but this accounts for only a small proportion of the total disease burden. Using the developmentally estrogenized mouse model, an alternative role for estrogens as a predisposing factor for prostate diseases was proposed: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to neoplasia. A combination therapy employing both differentiation therapy and hormone therapy may be effective in the treatment of advanced prostate cancers. Recent advances in the field of differentiation therapy have resulted in the development of novel retinoic acid metabolism blocking agents. Unlike previous differentiating agents such as the retinoids, these agents increase the endogenous levels of retinoic acid by inhibiting its breakdown in cancer cells.

[Limitations on the interpretation of prostate-specific antigen serum levels]. / Limiti nell'interpretazione dei livelli sierici dell'antigene specifico prostatico (PSA).

Recent data suggest that PSA expression can be directly influenced by some factors, independently from the variation in prostate cell growth. Some growth factors such as fibroblast growth factor, transforming growth factor beta and epidermal growth factor, seem to be directly involved in the regulation of mRNA-PSA expression, whereas androgens could have an indirect activity. On the basis of these experimental data, this review tries to analyze some limits of PSA and some recent data on the role of PSA-isoforms, in particular in the follow-up of prostate cancer patients submitted to radical prostatectomy or hormone-therapy. Moreover, relevant informations can be obtained analyzing the variance of PSA in patients submitted to intermittent androgen deprivation.

[Heredity and urologic tumors]. / Ereditarietà e tumori di interesse urologica.

Most human malignant tumours derive from a series of several mutations in cell growth regulatory genes. Neoplastic transformation is a multistep, or at times multigenic event where several mutations must intervene. Hereditary forms have been identified for a number of human neoplasias. In hereditary forms, the individual already inherits one or more of these mutations and assumes an increased risk of developing a specific carcinoma and at an earlier age. On the other hand, in sporadic forms, the risk is lower because the environmental factors must provoke in sequence all the mutations necessary for neoplastic transformation. These genic mutations are often associated with the deletion of oncosuppressor genes which negatively regulate cell proliferation and/or with the hyper-expression and activation of protoncogenes which favour cell proliferation. The products of these genes are often growth factors or receptors of growth factors. The present review analyses the definition and more or less proven identification of familial and hereditary forms in neoplasias of urological interest.

Intermittent androgen deprivation (IAD) in patients with localized prostate cancer and a biochemical progression after radical prostatectomy.

BACKGROUND: To analyze the modifications in serum PSA levels during IAD in patients with an initial PSA progression after radical retropubic prostatectomy (RRP). METHODS: Between February 1994 and May 1996, 34 consecutive patients with an initial PSA progression (> 0.4 ng/ml) after RRP were selected. All men had localized adenocarcinoma of the prostate, stage pT2 pN0 M0. Patients were offered IAD when PSA progressed over 0.4 ng/ml. The initial treatment period with complete androgen deprivation (CAD) lasted 24 weeks in all cases. After, an acceptable nadir PSA level was considered to be a value < or = 0.4 ng/ml. CAD was then with held until serum PSA increased to a value over 0.4 ng/ml. RESULTS: Follow-up ranges from 144 to 228 weeks. The median time for the first 5 treatment cycles was 32, 24, 28, 32 and 32 weeks respectively, with a median time "off" therapy that increased from 8 weeks (first cycle) to 22 weeks (fifth cycle). The median nadir PSA value during "on" treatment period was 0.20 ng/ml in all 5 cycles. So far, in none of the patients did a serum PSA fail to decrease during "on" treatment period. CONCLUSIONS: We suggest that IAD may be an effective therapy in patients with an initial PSA progression after RRP. However, large prospective studies are needed to confirm these results and to better understand the meaning of PSA variations.

[Role of nitric oxide in the urogenital system: physiology and pathology]. / Ruolo dell'ossido nitrico nell'apparato genito-urinario: fisiologia e patologia.

A review has been made on the role of nitric oxide in the physiology and pathophysiology of penis, bladder, prostate and the nervous structures involved in the urinary control. NO is an essential mediator in penile erection and his action can be modulated by sildenafil. Nitric oxide could be involved in bladder detrusor relaxation and in the development of interstitial cystitis. Little is known about the role of nitric oxide in the physiology and pathophysiology of the prostate: this molecule is released by the epithelial and stromal cells of the prostate, and by the prostatic nerves. Actually some studies hypothesize a role played by nitric oxide in benign prostatic hyperplasia development.

Pathology of BPH.

Much research has been conducted to determine which tissue (epithelium or stroma) in the prostate gives rise to benign prostatic hyperplasia (BPH). Considering that BPH displays two structural compartments, stromal and epithelial and that the periurethral and transitional regions are particularly involved, the immunohistochemical and regional evaluation of steroid receptors concentration, 5 alpha reductase, DHT and estrogen activity, may show important data on the role of these factors in BPH development. We started a immunohistochemical study on the epidermal growth factor (EGF) concentrations in the periurethral, central and pericapsular zones of BPH samples, considering the stroma-epithelium ratio; investigations are performed on BPH patients submitted to transvesical prostatectomy. Considering that the periurethral zone is particularly involved in BPH, the presence of high concentration of growth factors in this region, may support the concept of their involvement in BPH.

Plant extracts in BPH.

In Italy plant extracts represent 8.6% of all pharmacological prescriptions for Benign Prostatic Hyperplasia (data from 1991). This review evaluates all the suggested mechanisms of action for plant extracts. Recently we demonstrated an antiestrogenic effect of Serenoa Repens in BPH patients. Clinical trials with plant extracts have yielded conflicting results. In a recent review by Dreikorn and Richter, only five placebo controlled studies were found. Moreover, as opposed to chemically defined drugs, it is possible that for these extracts the active ingredients are not known; consequently pharmacodynamic and pharmacokinetic data are often missing. The International Consultation of Benign Prostatic Hyperplasia (Paris, June 1991) concluded that, to date, phytotherapeutic agents must be considered as a symptomatic treatment. Now more adequate pharmacological and clinical studies, placebo controlled, should determine the exact role of these drugs in the treatment of BPH.