Roberto Castiglione

Sperm parameter abnormalities, low seminal fructose and reactive oxygen species overproduction do not discriminate patients with unilateral or bilateral post-infectious inflammatory prostato-vesiculo-epididymitis.

We have shown that patients with prostato-vesiculo-epididymitis (PVE) have the worst sperm output compared to patients with prostato-vesiculitis or prostatitis alone. The present study was undertaken to closely examine whether unilateral or bilateral PVE had a different impact on sperm parameters, seminal fructose levels and reactive oxygen species (ROS) overproduction. To accomplish this, 78 patients with persistent post-infectious inflammatory PVE, clearly identified by scrotal and transrectal ultrasonography, and 30 patients with asymptomatic post-infectious inflammatory prostatitis (control group) underwent semen analysis (including seminal leukocyte concentration and number of spermiophagies), seminal fructose measurement and sperm ROS production from 45 and 90% Percoll fractions. Fifty patients turned out to have PVE bilaterally, whereas the remaining 28 had unilateral PVE. Patients with bilateral PVE had sperm concentration and total sperm number significantly lower than those found in patients with unilateral PVE. The other sperm parameters, the physicochemical properties (hyperviscosity, the presence of nonspecific agglutination, delayed liquefaction), seminal fructose levels and ROS production in both 45 and 90% Percoll fractions turned out similar between the two groups. Patients with bilateral or unilateral PVE had sperm parameters, seminal fructose levels and ROS production significantly worst than those found in patients with prostatitis alone. In conclusion, although patients with bilateral PVE had a decreased number of spermatozoa, the other sperm parameters and seminal fructose levels did not reflect the extension of PVE. Therefore, the diagnosis of unilateral or bilateral involvement of this complicated form of male accessory gland infection relies on scrotal and transrectal ultrasonography.

Transrectal ultrasonography in infertile patients with persistently elevated bacteriospermia

AIM To identify and define prostate and seminal vesicle abnormalities in patients with chronic male accessory gland infection (MAGI) who failed to respond to antibacterial treatment. METHODS We selected 67 consecutive patients with MAGI and persistently elevated bacteriospermia (=or>10(6) colony forming units [CFU]/mL) after three antibiotic courses. Fourteen infertile patients with initial chronic microbial (=or>10(6) CFU/mL) MAGI who responded to antibacterial treatment (<10(3) CFU/mL) served as a control group. All patients and controls underwent transrectal ultrasonography (TRUS) scans and semen analysis. Patients with low seminal plasma volume (<1.5 mL) underwent both pre-ejaculatory and post-ejaculatory TRUS examination. RESULTS TRUS revealed multiple abnormalities indicative of: (i) bilaterally extended prostato-vesiculitis (group A: 52 cases, 77.6%) (nine of these patients also had micro-emphysematous prostate abscess); and (ii) prostato-vesiculitis with unilateral or bilateral sub-obstruction of the ejaculatory ducts (group B: 15 cases, 22.4%). Mean sperm concentration, total sperm number, ejaculate volume and pH value were significantly higher in group A than in group B. In addition, sperm forward motility and the percentage of normal forms were significantly worse than in controls, whereas leukocyte concentration was significantly higher in group A. Group B patients had all sperm parameters, but their pH values, significantly different from those of controls. CONCLUSION Although antibiotic therapy is considered suitable when microbial MAGI is suspected, it is impossible to account for a poor response to antibiotics merely on the basis of conventional criteria (clinical history, physical and ejaculate signs). Thus, TRUS may be helpful in the follow-up of these patients.

Relationship of semen hyperviscosity with IL‐6, TNF‐α, IL‐10 and ROS production in seminal plasma of infertile patients with prostatitis and prostato‐vesiculitis

Changes in levels of oxidative damage products in semen and their relationship to seminal fluid viscosity (SFV) have recently received increasing research interest. We analysed whether SFV was associated with ROS generation, levels of cytokines TNF‐alpha (TNF‐α), IL‐6 and IL‐10 and seminal leucocyte concentration, and whether ROS production was related to the extent of infections/inflammations at one (prostatitis) or two (prostato‐vesiculitis) male accessory glands. We studied 169 infertile patients, with chronic bacterial prostatitis (PR, n = 74) and/or bilateral prostato‐vesiculitis (PV, n = 95), as diagnosed by the ultrasound (US) criteria. Healthy fertile men (n = 42) served as controls. In the PV patient group, SFV, semen characteristics and ROS production had median values that were significantly higher than those found in PR patients and controls, although other sperm variables had values significantly lower than those found in PR patients or controls. In PV infertile patients, ROS generation and pro‐inflammatory cytokines levels were higher than those found in PR infertile patients and controls, although seminal IL‐10 levels in PV and PR patients were lower than those found in the controls. In PR patients, the levels of SFV were positively related to TNF‐α (r = 0.67; P < 0.01), fMLP‐stimulated ROS production in the 45% Percoll fraction (r = 0.687, P < 0.01) and the 90% Percoll fraction in basal condition (r = 0.695, P < 0.01), and after fMLP‐stimulation (r = 0.688, P < 0.01). Thus, our data indicated that seminal hyperviscosity is associated with increased oxidative stress in infertile men and increased pro‐inflammatory interleukins in patients with male accessory gland infection, more when the infection was extended to the seminal vesicles.

High Frequency of Chronic Bacterial and Non-Inflammatory Prostatitis in Infertile Patients with Prostatitis Syndrome Plus Irritable Bowel Syndrome

Background Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis. Methodology/Principal Findings This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%). They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II) and lower of non-inflammatory prostatitis (category IIIB), compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA) resulted similar. Conclusions/Significance Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis.

Expression of SpanX mRNA in testicular germ cell tumors

The function of SpanX proteins is unknown, evidence is accumulating to suggest their involvement in tumorigenesis. A locus in Xq27, where the SpanX gene family is located, has been associated with testicular germ cell tumor (TGCT) onset. Therefore, we evaluated the presence of SpanX mRNA in six TGCT cases by RT-PCR. The results showed that SpanX mRNA is present in TGCT, confirming transcriptional activity of these genes in such tumors.

Expression of SPANX proteins in normal prostatic tissue and in prostate cancer

The sperm protein associated with the nucleus in the X chromosome (SPANX) gene family encodes for proteins that are not only expressed in germ cells, but also in a number of tumors. In addition, SPANX genes map in an interval of the X chromosome (namely, Xq27), which has been found to be associated with familial prostate cancer by linkage analysis. The aim of this study was therefore to evaluate SPANX protein expression in normal prostate tissues and in prostate carcinoma. For this purpose, formalin-fixed and paraffin-embedded sections obtained from 15 normal (at autopsy) donors and 12 men with prostate cancer were analyzed by immunohistochemistry. About 40% of both normal and tumor prostate samples resulted SPANX positive. Signals were exclusively within the nucleus in normal prostate cells, whereas both nuclear and cytoplasmic positivity was observed in tumor cells. In conclusion, these findings showed that SPANX genes are expressed in both normal and tumor prostate gland, but the latter showed a peculiar cytoplasmic staining positivity. This suggests a possible association between SPANX over expression and prostate cancer development. Additional studies are needed to corroborate this hypothesis.

Chronic bacterial prostatitis and irritable bowel syndrome: effectiveness of treatment with rifaximin followed by the probiotic VSL#3

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis (PV) or prostate-vesiculo-epididymitis (PVE). A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis (CBP) and irritable bowel syndrome (IBS) were randomly prescribed rifaximin (200 mg, 2 tablets bid, for 7 days monthly for 12 months) and probiotic containing multiple strains VSL#3 (450 × 109 CFU per day) or no treatment. Ninety-five of them (89.6%) complied with the therapeutic plan and were included in this study. Group A = “6Tx/6-”: treatment for the initial 6 and no treatment for the following 6 months (n = 26); Group B = “12Tx”: 12 months of treatment (n = 22); Group C = “6-/6Tx”: no treatment for the initial 6 months and treatment in the last 6 months (n = 23); Group D = “12-”: no treatment (n = 24). The patients of Groups A = “6Tx/6-” and B = “12Tx” had the highest frequency of chronic prostatitis (88.5% and 86.4%, respectively). In contrast, group “12-”: patients had the lowest frequency of prostatitis (33.4%). The progression of prostatitis into PV in groups “6Tx/6-” (15.5%) and “6-/6Tx” (13.6%) was lower than that found in the patients of group “12-” (45.8%). Finally, no patient of groups “6Tx/6-” and “6-/6Tx” had PVE, whereas it was diagnosed in 20.8% of group “12-” patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.

Expression of STRBP mRNA in patients with cryptorchidism and Down’s syndrome

The most frequent defect of the male urogenital tract at birth is cryptorchidism. Cryptorchidism causes primitive testicular pathology responsible for infertility. Men with Down’s syndrome (DS) have an increased risk of cryptorchidism. The spermatid perinuclear RNA-binding protein (STRBP) gene codifies a microtubule-associated RNA-binding protein and it is highly expressed in the testis as well as in the brain. At both levels, this gene seems to play a relevant role in the regular development of these organs. These observations prompted us to evaluate the expression of STRBP mRNA in 5 DS men with cryptorchidism and 5 normal healthy men (controls) by quantitative Real Time PCR in peripheral blood leukocytes. We found a decreased expression of the STRBP gene in men with DS and cryptorchidism compared with controls. This finding suggests that the impaired expression of this gene in DS may play a pathogenetic role in the altered brain and testicular development in subjects with DS and cryptorchidism.

PARP1 and CASP3 gene expression in a patient with multiple head and neck squamous cell carcinoma and Parkinson disease

Dear Sir,This letter describes an interesting case of a 98-year-oldwoman with multiple head and neck squamous cell carci-noma (HNSCC) and Parkinson disease (PD). The followingsquamous cell cancers were discovered in this patient: (1)squamous cell carcinoma of the tongue, diagnosed andexcised in 2004 with complete clinical recovery; and (2) insitu squamous cell carcinoma of the right cheek and theneck, diagnosed in 2009. She also presented difficulty inthe dexterity of the right hand and a typical PD asymmetricpresentation. Indeed, the patient had a rest tremor andcogwheel rigidity, bradykinesia bilaterally, stooped pos-ture, turns en bloc, and decreased armswing on the right.These symptoms were responsive to the administration of

A high percentage of skin melanoma cells expresses SPANX proteins.

The expression of SPANX (sperm protein associated with the nucleus in the X chromosome) gene family has been reported in many tumors, such as melanoma, myeloma, glioblastoma, breast carcinoma, ovarian cancer, testicular germ cell tumors, and hematological malignancies. However, no systematic approach has so far been devised to estimate the percentage of cancer cells expressing SPANX. This study was undertaken to quantify the expression of SPANX proteins in melanomas. The expression of SPANX proteins was evaluated by immunohistochemistry in normal skin (n = 12), melanomas (n = 21), and benign nevi (n = 10), using a polyclonal antibody raised in our laboratory. Seventeen of the 21 melanomas (80.9%) examined expressed SPANX proteins. A high percentage of their cells (49.0% ± 5.5%) stained positively for SPANX proteins compared with no expression found in normal skin cells. Benign nevi had an intermediate number of cells expressing SPANX proteins (25% ± 8.5%), which resulted significantly higher than normal skin cells and significantly lower than skin melanoma cells. In melanoma cells, the labeling was mostly nuclear, sometimes incomplete or limited to the perinuclear wall, even if cytoplasmic staining was also seen in SPANX-positive tumor cells. In contrast, the 5 of 10 SPANX-positive nevi had a clear nuclear localization of the signal. These data suggest that the SPANX protein family is expressed in the vast majority of the melanomas tested. The mechanism(s), which brings up SPANX gene expression and the role of these proteins are not known.