Oxidative stress and male infertility.

BACKGROUND: Between 30% and 80% of patients with male infertility produce excessive reactive oxygen species (ROS) in their ejaculate even though the cause of male infertility is unexplained in approximately half of cases. The strong connection between oxidative stress (OS) and male infertility has led recent investigators to propose the term "Male Oxidative Stress Infertility (MOSI)" to describe OS-associated male infertility. METHODS: We searched the PubMed database for original and review articles to survey the effects of OS on male infertility, and then verified the effects and treatments. MAIN FINDINGS: Seminal plasma contains many antioxidants that protect sperm from ROS, because low amounts of ROS are required in the physiological fertilization process. The production of excessive ROS causes OS which can lower fertility through lipid peroxidation, sperm DNA damage, and apoptosis. Several assays are available for evaluating OS, including the MiOXSYS® analyzer to measure oxidation-reduction potential. Several measures should be considered for minimizing OS and improving clinical outcomes. CONCLUSION: Accurately diagnosing patients with MOSI and identifying highly sensitive biomarkers through proteomics technology is vital for better clinical outcomes.

[A Case of Solitary Metastasis of Renal Cell Carcinoma to the Thyroid Gland].

A case of solitary metastasis of renal cell carcinoma to the thyroid gland is presented. The patient was a 82-year-old man found to have an abnormal mass in his neck. He had a past history of renal clear cell carcinoma of the left kidney (pT1aN0M0, G1>2, alveolar type, clear cell subtype), which had been resected 12 years previously. Ultrasonography revealed a tumor mass in the right hemithyroid gland. This time fine needle biopsy of the thyroid tumor suggested metastatic thyroid carcinoma. Right hemithyroidectomy was performed last year. The histopathological findings were suggestive of clear cell carcinoma, thus metastatic renal carcinoma was diagnosed. This is the 26th case of thyroid solitary metastasis of clear cell renal cell carcinoma reported in Japan to date.

Development and internal validation of a nomogram for predicting stone-free status after flexible ureteroscopy for renal stones.

OBJECTIVE: To develop and internally validate a preoperative nomogram for predicting stone-free status (SF) after flexible ureteroscopy (fURS) for renal stones, as there is a need to predict the outcome of fURS for the treatment of renal stone disease. PATIENTS AND METHODS: We retrospectively analysed 310 fURS procedures for renal stone removal performed between December 2009 and April 2013. Final outcome of fURS was determined by computed tomography 3 months after the last fURS session. Assessed preoperative factors included stone volume and number, age, sex, presence of hydronephrosis and lower pole calculi, and ureteric stent placement. Multivariate logistic regression analysis with backward selection was used to model the relationship between preoperative factors and SF after fURS. Bootstrapping was used to internally validate the nomogram. RESULTS: Five independent predictors of SF after fURS were identified: stone volume (P < 0.001), presence of lower pole calculi (P = 0.001), operator with experience of >50 fURS (P = 0.026), stone number (P = 0.075), and presence of hydronephrosis (P = 0.047). We developed a nomogram to predict SF after fURS using these five preoperative characteristics. Total nomogram score (maximum 25) was derived from summing individual scores of each predictive variable; a high total score was predictive of successful fURS outcome, whereas a low total score was predictive of unsuccessful outcome. The area under the receiver operating characteristics for nomogram predictions was 0.87. CONCLUSION: The nomogram can be used to reliably predict SF based on patient characteristics after fURS treatment of renal stone disease.

[A Case of Kartagener's Syndrome in Infertile Male Patients].

The patient was a 33-year-old man attending the infertility clinic with primary infertility of 3 years duration. The semen examination showed oligozoospermia and suspected primary male infertility. He had a history of chronic sinusitis and respiratory disease. His chest X-ray showed dextrocardia. Abnormality of the ultrastructure of the cilia of the tract epithelium was found by electron microscopy, and further examination revealed bronchoectasis. We gave him a diagnosis of Kartagener syndrome from these findings. Kartagener syndrome consists of bronchiectasis, sinusitis and situs inversus and is considered a form of primary ciliary dyskinesia (PCD). PCD is also a cause of motor impairment of sperm flagella. This case had successful in-vitro fertilization pregnancy with spermatozoa from the patient.

[Case of azoospermia patient with a chromosomal abnormality considered a ring Y chromosome].

A 43-year-old man came to our clinic complaining of infertility and semen analysis showed azoospermia. Analysis of chromosomes showed a mosaic 45, XO/46, X, ＋mar1/46, X, ＋mar2 karyotype, and the marker chromosomes were considered to be two kinds of ring Y chromosomes. Y chromosome microdeletion analysis showed partial deletion of Azoospermic Factor (AZF) a, and complete deletion of AZFb and AZFc. The patient gave up having a child because these results indicated that no sperm would be collected even if Testicular Sperm Extraction (TESE) were performed.

[Sharing information of urological cancer patient in terminal stage using Cybozulive® for home medical care].

It is very important to share patient information because home patient care involves several different specialties of care. We introduced Cybozulive ® , a cloud-based free groupware, for 14 terminal-stage patients with urological cancer to share information among doctors and co-medical staff. This system enables access to patient information regardless of time and place. Of the 14 patients (mean age 74.4 years), 11 died of cancer. The average period in which Cybozulive® was used for the patients was 210 days. The average number of entries to the electronic bulletin board in this period was 88.4. We were able to obtain more information about the patients from the website. There was no difference in the average number of times that the patient consulted the out patient clinic before and after the introduction of Cybozulive® (before 7.0 ; after 6.3). After introduction of this system, eleven patients were hospitalized in our department 21 times. Eighteen of these 21 times, since we had acquired patient information from the website beforehand, there was a quick response for management of the emergency admission. This system could be used to construct a network for home care and may be helpful for sharing patient information in homecare.

[Clinical investigation of male infertile patients with chromosomal anomalies].

We investigated 470 male patients who came to the Reproduction Medical Center of Yokohama City University Medical Center complaining of infertility between April 2,000 and August 2013. We analyzed the chromosomes of 90 patients whose sperm concentration was below 1.0 × 107/ml. Nineteen of the 90 (21.1%) patients showed sex chromosomal anomalies including 12 Klinefelter syndrome (47, XXY or 46, XY/47, XXY), Robertsonian translocation, 2 autosome-autosome translocation, Y-autosome translocation, 46, X with marker chromosome (46, Xmar⁺), XX male and Y chromosome macrodeletion (46, XYq-). While patients with chromosomal abnormalities except XX male or some of 46, XYq- may succeed in reproduction using testicular sperm extraction-intracytoplasmic sperm injection, we need to inform the patients about the risks of chromosomal abnormalities in the resulting fetus.

Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis.

The pathogenesis of non-alcoholic steatohepatitis (NASH) involves the simultaneous interaction of multiple factors such as lipid accumulation, oxidative stress, and inflammatory response. Here, the effect of human serum albumin (HSA) fused to thioredoxin (Trx) on NASH was investigated. Trx is known to have anti-oxidative, anti-inflammatory, and anti-apoptotic effects. However, Trx is a low molecular weight protein and is rapidly eliminated from the blood. To overcome the low availability of Trx, HSA-Trx fusion protein was produced and evaluated the therapeutic effect on high-fat diet (HFD)-induced NASH model mice. HSA-Trx administered before the formation of NASH pathology showed it to have a preventive effect. Specifically, HSA-Trx was found to prevent the pathological progression to NASH by suppressing lipid accumulation, liver injury markers, and liver fibrosis. When HSA-Trx was administered during the early stage of NASH there was a marked reduction in lipid accumulation, inflammation, and fibrosis in the liver, indicating that HSA-Trx ameliorates NASH pathology. The findings indicate that HSA-Trx influences multiple pathological factors, such as oxidative stress, inflammation, and apoptosis, to elicit a therapeutic benefit. HSA-Trx also inhibited palmitic acid-induced lipotoxicity in HepG2 cells. Taken together, these results indicate that HSA-Trx has potential as a therapeutic agent for NASH pathology.

[A suspected case of extra-gonadal germ cell tumor complicated with choriocarcinoma syndrome].

Our patient was a 31-year-old man who presented with right flank pain. Computed tomography revealed multiple tumors in the liver and lungs, with marked elevation of serum human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) levels. In addition, no testicular abnormalities were detected by palpation or ultrasonography. On the bases of these results, the patient was diagnosed with extragonadal germ cell tumor and was therefore started on chemotherapy with bleomycin, etoposide, and cisplatin (BEP). However, the result of a subsequent blood test showed marked pancytopenia at the initial stage of treatment. We speculated that the cause of anemia was not only bone marrow suppression but also intratumoral hemorrhage, collectively termed choriocarcinoma syndrome. After conservative treatment involving blood transfusion and administration of granulocyte colony-stimulating factor, he recovered. After several chemotherapy sessions, the levels of all tumor markers returned to normal. Finally, the patient underwent hepatectomy for residual tumors ; but, the resected specimen showed no viable cancer cells. Currently, the patient is free from disease since the last chemotherapy session, administered 5 months ago.

Dynamic transition of molecular subtypes in relapsed small cell lung cancer treated with multimodal therapy: A case report.

Several transcription factors in small cell lung cancer (SCLC), including achaete-scute homolog 1 (ASCL1) and neurogenic differentiation factor 1 (NEUROD1), contribute to rapid tumor growth and early metastatic dissemination. Recent studies suggested that these molecular subtypes represent neuroendocrine differentiation in dynamic SCLC evolution. In the present case, a 62-year-old man was diagnosed with limited disease SCLC originating from the right upper lobe. Biopsy specimens were positive for ASCL1 but negative for NEUROD1. Six months after concurrent chemoradiotherapy and prophylactic cranial irradiation, the primary tumor had regrown and salvage surgery was performed. The pathological diagnosis was recurred SCLC, and postoperative histopathology was positive for both ASCL1 and NEUROD1. The patient was subsequently followed up; however, he had multiple bone metastases 9 months after surgery. It was speculated that the shift to NEUROD1-high expression in tumor cells surviving concurrent chemoradiation therapy may be related to the poor outcome after combined modality treatment.