Safety and efficacy of low intensity shockwave (LISW) treatment in patients with erectile dysfunction.

UNLABELLED: The primary goal in the management strategy of a patient with ED would be to determine its etiology and cure it when possible, and not just to treat the symptoms alone. One of the new therapeutic strategies is the use of low intensity extracorporeal shockwave (LISW) therapy. The mechanism of shockwave therapy is not completely clear. It is suggested that LISW induces neovascularization and improvement of cavernosal arterial flow which can lead to an improvement of erectile function by releasing NO, VEGF and PCNA. MATERIALS AND METHODS: 31 patients between February and June 2013 with mild to severe ED and non-Phosphodiesterase 5 inhibitors responders were enrolled. Patients underwent four weekly treatment sessions. During each session 3600 shocks at 0.09mJ/ mm2 were given, 900 shocks at each anatomical area (right and left corpus cavernosum, right and left crus). Improvement of the erectile function was evaluated using the International Index of Erectile Function (IIEF-EF), the Sexual Encounter Profile (SEP) diaries (SEP-Questions 2 and 3) and Global Assessment Questions (GAQ-Q1 and GAQ-Q2). RESULTS: At 3-month follow-up IIEF-EF scores improved from 16.54±6.35 at baseline to 21.03±6.38. Patients answering 'yes' to the SEP-Q2 elevated from 61% to 89% and from 32% to 62% in the SEP-Q3. A statistically significant improvement was reported to the Global Assessment Questions (GAQ-Q1 and GAQ-Q2). CONCLUSION: In conclusion, we can affirm that LISW is a confirmed therapeutic approach to erectile dysfunction that definitely needs more long-term trials to be clarified and further verified.

Safety and efficacy of low intensity shockwave (LISW) treatment in patients with erectile dysfunction

ABSTRACT The primary goal in the management strategy of a patient with ED would be to determine its etiology and cure it when possible, and not just to treat the symptoms alone. One of the new therapeutic strategies is the use of low intensity extracorporeal shockwave (LISW) therapy. The mechanism of shockwave therapy is not completely clear. It is suggested that LISW induces neovascularization and improvement of cavernosal arterial flow which can lead to an improvement of erectile function by releasing NO, VEGF and PCNA. Materials and Methods: 31 patients between February and June 2013 with mild to severe ED and non-Phosphodiesterase 5 inhibitors responders were enrolled. Patients underwent four weekly treatment sessions. During each session 3600 shocks at 0.09mJ/ mm2 were given, 900 shocks at each anatomical area (right and left corpus cavernosum, right and left crus). Improvement of the erectile function was evaluated using the International Index of Erectile Function (IIEF-EF), the Sexual Encounter Profile (SEP) diaries (SEP-Questions 2 and 3) and Global Assessment Questions (GAQ-Q1 and GAQ-Q2). Results: At 3-month follow-up IIEF-EF scores improved from 16.54±6.35 at baseline to 21.03±6.38. Patients answering ‘yes’ to the SEP-Q2 elevated from 61% to 89% and from 32% to 62% in the SEP-Q3. A statistically significant improvement was reported to the Global Assessment Questions (GAQ-Q1 and GAQ-Q2). Conclusion: In conclusion, we can affirm that LISW is a confirmed therapeutic approach to erectile dysfunction that definitely needs more long-term trials to be clarified and further verified.

Treatment of bilateral varicocele and other scrotal comorbidities using a single scrotal access: our experience on 34 patients.

INTRODUCTION: Varicocele is the main cause of infertility in male and the most correctable cause of it too. In this study, we present our experience on 34 patients affected by bilateral varicocele and other scrotal comorbidities treated underwent surgery with a scrotal access. MATERIALS AND METHODS: 34 patients were enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele and other comorbidities like right hydrocele, left hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal bilateral varicocelectomy under local anesthesia. RESULTS AND DISCUSSION: At 6 months, no other complications were reported. No case of testicular atrophy was observed. None had recurrence of varicocele. All scrotal comorbidities were treated as well. CONCLUSION: Scrotal access with local anesthesia is a safe and useful technique to treat patients with bilateral varicocele and other scrotal comorbidities.

Toward an improved prediction of human in vivo brain penetration.

The penetration of drugs into the central nervous system is a composite of both the rate of drug uptake across the blood-brain barrier and the extent of distribution into brain tissue compartments. Clinically, positron emission tomography (PET) is the primary technique for deriving information on drug biodistribution as well as target receptor occupancy. In contrast, rodent models have formed the basis for much of the current understanding of brain penetration within pharmaceutical Drug Discovery. Linking these two areas more effectively would greatly improve the translation of candidate compounds into therapeutic agents. This paper examines two of the major influences on the extent of brain penetration across species, namely plasma protein binding and brain tissue binding. An excellent correlation was noted between unbound brain fractions across species (R(2) > 0.9 rat, pig, and human, n = 21), which is indicative of the high degree of conservation of the central nervous system environment. In vitro estimates of human brain-blood or brain-plasma ratios of marketed central nervous system drugs and PET tracers agree well with in vivo values derived from clinical PET and post-mortem studies. These results suggest that passive diffusion across the blood-brain barrier is an important process for many drugs in humans and highlights the possibility for improved prediction of brain penetration across species.

Synthesis and biological evaluation of pro-drugs of GW196771, a potent glycine antagonist acting at the NMDA receptor.

GW196771 is a potent antagonist of the modulatory glycine site of the N-methyl-D-aspartate (NMDA) receptor exhibiting outstanding in vivo profile in different animal models of chronic pain. With the aim to maximize the drug delivery to the target organs a suitable "pro-drug approach" was attempted; in this regards two conjugates of GW196771 with nutrients actively transported into the brain, namely adenosine and glucose, were prepared and investigated. These compounds, were evaluated in vitro in terms of their stability in rat plasma and in vivo on rats. Although an improvement was observed in terms of brain penetration of the esters vs. the parent compound, the amount of the latter did not increase significantly, probably due to some degradation events in the brain, different from the expected ester hydrolysis, resulting in a reduced availability of GW196771.

Development and validation of a column-switching high-performance liquid chromatographic method for the determination of sanfetrinem in rat and dog plasma by direct injection.

A direct injection column-switching HPLC method was developed and validated for quantification of sanfetrinem in rat and dog plasma. Following dilution with buffer, samples were directly injected onto the system. The analyte was retained in an enrichment column while endogenous plasma components were eluted to waste. Sanfetrinem was then back-flushed to the analytical column for separation and quantification with an ultraviolet detector. Sample batch size was increased by adding a washing phase of the enrichment column and by alternating the injections between two enrichment columns. The method is very simple and sample preparation is minimal. The method has been fully validated and shown to be specific, accurate and reproducible.

Overexpression of H ferritin and up-regulation of iron regulatory protein genes during differentiation of 3T3-L1 pre-adipocytes.

The role of iron-dependent oxidative metabolism in protecting the oxidable substrates contained in mature adipocytes is still unclear. Because differentiation increases ferritin formation in several cell types, thereby leading to an accumulation of H-rich isoferritins, we investigated whether differentiation affects iron metabolism in 3T3-L1 pre-adipocytes. To this aim, we evaluated the expression of the genes coding for the H and L ferritin subunits and for cytoplasmic iron regulatory protein (IRP) during the differentiation of 3T3-L1 cells in adipocytes induced by the addition of isobutylmethylxanthine, insulin, and dexamethasone. Differentiation enhanced ferritin formation and caused overexpression of the H subunit, thus altering the H/L subunit ratio. Northern blot analysis showed increased levels of H subunit mRNA. A gel retardation assay of cytoplasmic extract from differentiated cells, using an iron-responsive element as a probe, revealed enhanced an RNA binding capacity of IRP1, which correlated with the increase of IRP1 mRNA. The observed correlation between differentiation and iron metabolism in adipocytes suggests that an accumulation of H-rich isoferritin may limit the toxicity of iron in adipose tissue, thus exerting an antioxidant function.

Oxalomalate, a competitive inhibitor of aconitase, modulates the RNA-binding activity of iron-regulatory proteins.

We investigated the effect of oxalomalate (OMA, alpha-hydroxy-beta-oxalosuccinic acid), a competitive inhibitor of aconitase, on the RNA-binding activity of the iron-regulatory proteins (IRP1 and IRP2) that control the post-transcriptional expression of various proteins involved in iron metabolism. The RNA-binding activity of IRP was evaluated by electrophoretic mobility-shift assay of cell lysates from 3T3-L1 mouse fibroblasts, SH-SY5Y human cells and mouse livers incubated in vitro with OMA, with and without 2-mercaptoethanol (2-ME). Analogous experiments were performed in vivo by prolonged incubation (72 h) of 3T3-L1 cells with OMA, and by injecting young mice with equimolar concentrations of oxaloacetate and glyoxylate, which are the precursors of OMA synthesis. OMA remarkably decreased the binding activity of IRP1 and, when present, of IRP2, in all samples analysed. In addition, the recovery of IRP1 by 2-ME in the presence of OMA was constantly lower versus control values. These findings suggest that the severe decrease in IRP1 RNA-binding activity depends on: (i) linking of OMA to the active site of aconitase, which prevents the switch to IRP1 and explains resistance to the reducing agents, and (ii) possible interaction of OMA with some functional amino acid residues in IRP that are responsible for binding to the specific mRNA sequences involved in the regulation of iron metabolism.

Detection of human T-cell lymphotrophic virus type I in archival tissue specimens.

OBJECTIVE AND DESIGN: To develop a method for the detection of human T-cell lymphotropic virus type I (HTLV-I) in archival biopsy specimens. A polymerase chain reaction-based gene amplification method was developed to detect HTLV-I proviral DNA in paraffin-embedded specimens. The specificity of the polymerase chain reaction products was controlled by Southern blot analysis using a nested oligonucleotide probe and by nucleotide sequencing. The nucleophosmin gene and the T-cell receptor-gamma gene were used as controls for the integrity and adequacy of total DNA and T-cell DNA, respectively. This study was conducted with patients referred to an academic medical center. Biopsy specimens were obtained from lesional skin or lymph node from Japanese patients with HTLV-I seropositive adult T-cell leukemia/lymphoma. The main outcome measure was the ability to detect HTLV-I pX region proviral DNA. RESULTS: Comparative analysis of DNA extracted from fresh samples of the HTLV-I infected MT4T-cell line demonstrated that formalin fixation and paraffin embedding resulted in a 100-fold reduction in sensitivity of the assay. Nevertheless, HTLV-I pX sequences were still readily detectable in paraffin-embedded samples of MT4 T cells and adult T-cell leukemia/lymphoma specimens. Both formalin and B5 fixation were suitable for the assay that was 100% specific for HTLV-I-infected tissues. CONCLUSIONS: The use of this method should greatly facilitate investigation of the role of HTLV-I in human diseases by allowing analysis of a wide variety of archival tissue specimens. In addition, the controls designed for the current study can be used in a variety of other polymerase chain reaction-based studies of T cells to ensure against false-negative results caused by DNA degradation or inadequate T-cell density.

The Angelchik prosthesis in the surgical therapy of reflux oesophagitis. Short and long term results.

The authors report the results acquired from 1981 to 1985 using the Angelchik prosthesis in 22 patients with reflux oesophagitis resisting medical therapy for more than 6 months. Clinical evaluation has been done using Visick scale, as modified by Deakin. Clinical and instrumental controls have been done at 1 month, 12 months and 5-10 years after the operation. Intraoperative mortality and morbidity were zero. Complications directly related to the operation were: transitory dysphagia in 4 cases, persistent dysphagia in 3 cases, transitory gas bloat syndrome in 1 case and persistent gas bloat syndrome in another, persistent stenosis in 1 case and prosthesis dislocation in 6 cases. Clinical results were satisfactory (success rate: 90.9%) only in patients with a short term follow-up (30 days). The full rate of success has come down to 84.2% and 66.6% in patients having follow-ups respectively of 1 year and 5-10 years. The results are truly disappointing and the authors conclude that this procedure is not to be employed.

[Isolated thrombosis of the left brachiocephalic venous trunk]. / Trombosi isolata del tronco venoso brachio-cefalico sinistro.

Only Flower (1976) has reported an isolated obstruction of the left brachiocephalic venous trunk following the observation of a unilateral distension of the left superior jugular vein secondary to compression of the homolateral innominate vein during a type I dissecting aneurysm of the aorta. The rarity of the finding is the reason for the report of two cases of isolated thrombosis of the venous trunk in question observed almost simultaneously some 19 months earlier. In both cases it was possible to identify the aetiopathogenic causes as congenital or acquired constriction of the "aortosternal strait" associated with thrombophilic alteration to the blood coagulation system.

[A case of splenic abscess in a drug addict with acquired immunodeficiency syndrome]. / Su di un caso di ascesso splenico in tossicodipendente con sindrome da immunodeficienza acquisita.

The complex diagnostic procedure involved in a case of splenic abscess in a young drug addict as a result of septicaemia caused by streptococcus fascalis is described and discussed with an examination of the criteria in support of a more aggressive approach to the removal of septic foci in such patients with AIDS. It is concluded that such criteria are valid even when, as in the case described, splenectomy further depresses the immune system.

[Enzymatic reaction of the follicular cell population in the human appendix]. / Reazioni enzimatiche della popolazione follicolare in appendici umane.

Histochemical techniques were employed to determine acid phosphatase and alpha-naphthylesterase activities in follicular cells from the mucosa of surgically removed human appendixes. These very reactive cells are found in two areas: in the middle of the light centre and in the surroundings of this centre. The former are globose, arranged with a certain degree of order, and have a reticular anchorage that does not appear to be particularly affected by the physiological and pathological events that occur in the appendix, whereas those of the border vary in number or may even be absent. They have an elongated shape and are also anchored in a reticulum that in this case is more consistent. The result is that in certain forms of appendiceal disease the pale centre of the follicle is closed in a kind of shell formed of very reactive cells. The identification and significance of these two groups of cells of the light centre are discussed.

[Medical management of reflux esophagitis]. / La terapia medica delle esofagiti da reflusso.

When the cause of oesophagitis has been discovered, patients for whom surgical management is impossible may be successfully treated by improving oesophageal peristalsis, increasing the tone of the LES, and speeding up the emptying of the stomach. The best results are obtained in peptic oesophagitis, since the latest secretion-inhibiting drugs ensure constant reduction of the acidity of the gastric juice, as has been demonstrated by continuous pH monitoring.

[Notes on the use of the Angelchik-Cohen ring]. / Qualche rilievo sull'uso dell'anello di Angelchik e Cohen.

Results obtained by using Angelchik and Cohen's ring prosthesis in 10 patients with hernia due to sliding through the oesophageal hiatus of the diaphragm are reported. In 8 patients, the ring was perfectly tolerated and performed its antireflux and hernia containment functions. In the 2 other patients, however, the prosthesis rose to the mediastinum, causing hernia to recur in one case and leading to recurrence of symptomatology in the other.