Bi-layered adipose mesenchymal cell sheets improve bladder compliance in spinal cord-injured rats.

To improve bladder compliance in patients with low-compliance bladders, augmentation cystoplasty with the intestinal tract is performed. However, the use of the intestinal tract often leads to serious surgical complications. Tissue engineering technologies have the potential to improve bladder compliance without using the intestinal tract. In this study, we fabricated bi-layered adipose-derived mesenchymal cell (AMC) sheets and then determined whether the bi-layered AMC sheets could improve bladder compliance in rats with spinal cord injury (SCI). The abdominal adipose tissues of green fluorescence protein (GFP)-transfected Sprague-Dawley (SD) rats were harvested, and the attached and proliferating cells on type Ⅰ collagen were used as AMCs. The AMCs were then cultured on temperature-responsive culture dishes. After reaching over-confluence, the AMCs that maintained cell-cell contacts were detached from the dishes and applied to a gelatin hydrogel sheet. Then, another detached AMC monolayer was accumulated on the AMC monolayer-applied gelatin. Prior to 4 weeks of transplantation, the levels of T8-9 in the spinal cords of recipient SD rats were partially transected. After producing the bi-layered AMC sheets and the rats with SCI, the detrusor muscles of the anterior bladder walls of the rats with SCI were incised, and the bi-layered AMC sheet was patch-transplanted onto the exposed bladder epithelium (n = 8). As a control, the sham operation was performed (n = 7). Four weeks after the transplantation, bladder capacity and bladder compliance in AMC sheet-transplanted SCI-rats were significantly higher than those in sham-operated control SCI-rats. The smooth muscle layers in AMC sheet-transplanted bladders were significantly larger than those in control bladders. In addition, the collagen fibers in the AMC sheet-transplanted bladders were significantly smaller than those in the control bladders. Some GFP-positive transplanted AMCs differentiated into SMA- or desmin-positive cells. Furthermore, GFP-positive cells secreted transforming growth factor-ß1 or vascular endothelial growth factor. Therefore, this study showed that bi-layered AMC sheets could improve bladder compliance and bladder tissues in SCI rats.

Transient receptor potential ankyrin 1 channels in the bladder mediate low temperature elicited bladder overactivity in rats.

AIMS: This study aimed to investigate whether pathways involving transient receptor potential ankyrin 1 (TRPA1) channels in the urinary bladder mediate the bladder overactivity elicited by exposure to a low temperature in rats. METHODS: At postnatal week 10, female Sprague-Dawley (SD) rats were intraperitoneally injected with the TRPA1 channel antagonist, HC030031, at room temperature (RT) and subsequently exposed to low temperature (LT). Bladder specimens treated with HC030031 were evaluated for contractions through cumulative addition of the TRPA1 channel agonist trans-cinnamaldehyde. Two days before cystometric investigation, small interfering RNA (siRNA) targeting TRPA1 was transfected into urinary bladders. Then, cystometric investigations were performed on rats subjected to TRPA1 siRNA transfection at both RT and LT. Expression of TRPA1 channels in the urinary bladder was assessed through immunohistochemistry and real-time reverse transcription-polymerase chain reaction. RESULTS: At RT, micturition patterns were unaffected by HC030031 treatment. However, upon exposure to LT, rats treated with HC030031 exhibited a reduction of LT-elicited bladder overactivity, as evidenced by inhibited decreases in voiding interval, micturition volume, and bladder capacity. Additionally, HC030031 inhibited trans-cinnamaldehyde-induced contractions. Immunohistochemical analysis showed the presence of TRPA1 channels in the urinary bladder. Notably, rats with TRPA1 siRNA-transfected bladders could partially inhibit bladder overactivity during LT exposure. CONCLUSIONS: These findings indicate that pathways involving TRPA1 channels expressed in the urinary bladder could mediate the LT-elicited bladder overactivity.

Analysis of Neurogenic Bowel and Bladder Dysfunction Following Decompression Surgery for Cervical Spondylotic Myelopathy: A Prospective Cohort Study.

STUDY DESIGN: A prospective observational study. OBJECTIVES: To investigate preoperative prevalence of neurogenic bowel dysfunction and neurogenic bladder in patients with degenerative cervical myelopathy (DCM) and examine the degree and timing of symptom improvement after cervical decompression surgery. Factors contributing to symptom improvement were also analyzed. METHODS: Among 75 patients with DCM who underwent cervical decompression, Constipation Scoring System (CSS) score, International Prostate Symptoms Score (IPSS), and Japanese Orthopaedic Association (JOA) score were assessed before surgery and 1, 3, 6, and 12 months after. Prevalence rates were calculated. Data regarding patient age, sex, disease status, disease duration, lesion level, and score changes was prospectively recorded and analyzed. RESULTS: The prevalence rates of defecation and urinary dysfunction before surgery were 41.3% and 34.7%, respectively. Among the patients with defecation dysfunction, the number of patients who improved 1, 3, 6, and 12 months after surgery was 10, 9, 9, and 6, respectively. Among the patients with urinary dysfunction, the corresponding number of patients was 12, 10, 11, and 11, respectively. None of the factors we examined were significantly associated with improvement in either CSS or IPSS score; however, improvement of lower extremity JOA score tended to be associated with improvement in both. CONCLUSIONS: The prevalence of symptoms of defecation and urinary dysfunction in patients with DCM was 41.3% and 34.7%, respectively. Decompression surgery improved symptoms in 20% to 46% of patients.

Cold stress-induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of a M3 -muscarinic antagonist and a ß3 -adrenergic agonist.

OBJECTIVES: Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M3 -muscarinic receptor antagonist and a ß3 -adrenergic receptor agonist. METHODS: Ten-week-old female GK rats were fed a high-fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle, the M3 -muscarinic receptor antagonist solifenacin, the ß3 -adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M3 -muscarinic and ß3 -adrenergic receptors were investigated. RESULTS: After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle-, solifenacin-, or mirabegron-treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M3 -muscarinic and ß3 -adrenergic receptors were detected, the expression of M3 -muscarinic receptor mRNA was significantly higher than that of ß3 -adrenergic receptor mRNA. CONCLUSIONS: The cold stress-induced bladder overactivity was not improved by either the M3 -muscarinic receptor antagonist or the ß3 -adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M3 -muscarinic antagonists and ß3 -adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.

Walking-Evoked Erection in Patients with Lumbar Degenerative Diseases: Eight Cases and Review of the Literature.

STUDY DESIGN: Narrative review with a case illustration. PURPOSE: The purpose of this study was to evaluate the pathogenesis and outcome of therapy for walking-evoked erection in patients with lumbar degenerative diseases. OVERVIEW OF LITERATURE: Cauda equina compression due to lumbar degenerative diseases rarely cause a walking-evoked erection; however, no review has been undertaken of walking-evoked erection in patients with lumbar degenerative diseases. METHODS: A total of 1,570 male patients with lumbar degenerative diseases, who underwent surgery between April 2003 and June 2017, were evaluated; from these patients, participants with walking-evoked erection were selected. Preoperative clinical data of walking-evoked erection, paresthesia, and bladder and bowel function were assessed. In our study, the neurological status and the erectile function of each participant were retrospectively evaluated before and after surgery using the Japanese Orthopedic Association score and the Overactive Bladder Symptom Score. RESULTS: Among the 1,570 male patients screened in our department, eight patients (0.51%, 8/1,570) presented with walking-evoked erection accompanied by cauda equina symptoms. In six of the patients, the erectile symptoms were associated with paresthesia in the genitalia or perianal region. Of the six patients evaluated for bladder dysfunction, all were diagnosed with prostatic hyperplasia, while four were diagnosed with an overactive bladder. In all patients, walking-evoked erection disappeared entirely after surgery. CONCLUSIONS: This study comprises the first review of walking-evoked erection in patients with lumbar degenerative diseases. We speculate that sensory input, such as paresthesia in the genitalia or perianal region stimulates the pelvic or perineal nerves through the pudendal nerve and induces reflexogenic erections.

Improvement in Neurogenic Bowel and Bladder Dysfunction Following Posterior Decompression Surgery for Cauda Equina Syndrome: A Prospective Cohort Study.

OBJECTIVE: The mechanisms of neurogenic bowel dysfunction (NBD) and neurogenic bladder (NB), which are major consequences of spinal cord injury and occasionally degenerative lumbar disease. The following in patients with cauda equina syndrome who underwent posterior decompression surgery was investigated: (1) the preoperative prevalence of NBD and NB, measured using the Constipation Scoring System (CSS) and International Prostate Symptoms Score (IPSS); (2) the degree and timing of postoperative improvement of NBD and NB. METHODS: We administered the CSS and IPSS in 93 patients before surgery and at 1, 3, 6, and 12 months postoperatively. We prospectively examined patient characteristics, Japanese Orthopaedic Association (JOA) score, and postoperative improvements in each score. RESULTS: The prevalence of symptomatic defecation and urinary symptoms at admission were 37 patients (38.1%) and 31 patients (33.3%), respectively. Among the symptomatic patients with defecation problems, 12 patients had improved at 1 month, 13 at 3 months, 14 at 6 months, and 13 at 12 months postoperatively. Among the symptomatic patients with urinary problems, 5 patients improved at 1 month, 11 at 3 months, 6 at 6 months, and 10 at 1 year postoperatively. Comparing patients with improved versus unimproved in CSS, the degree of JOA score improvement was a significant prognosis factor (p < 0.05; odds ratio, 1.05). CONCLUSION: The prevalence of symptomatic defecation and urinary symptoms in patients with cauda equina syndrome was 38.1% and 33.3%, respectively. Decompression surgery improved symptoms in 30%-50%. These effects were first observed 1 month after the operation and persisted up to 1 year.

Therapeutic effects of Choreito, a traditional Japanese (Kampo) medicine, on detrusor overactivity induced by acetic acid in rats.

Choreito (CRT), a traditional Japanese (Kampo) medicine, is widely used for the treatment of overactive bladder (OAB) and other lower urinary tract symptoms in Japan. This study aimed to identify the effects and therapeutic mechanism of CRT on the improvement of detrusor overactivity (DO) using an experimental rat model. Forty-five female Sprague-Dawley rats were equally divided into three groups: intravesical saline instillation with normal food (normal group), intravesical acetic acid (AA) instillation with normal food (AA group), and intravesical AA instillation with CRT (AA with CRT group). To induce a decrease in bladder capacity, instillation of 0.2% AA was used based on prior studies. Cystometric investigation was employed to clarify the effects of AA and CRT. Microcirculation was performed using a laser blood flowmeter, and the localization of hypoxia-inducible factor 1α (HIF1α) was assessed by immunohistochemistry. The bladder capacities of the normal, AA, and AA with CRT groups were 1.2 ± 0.3 mL, 0.4 ± 0.1 mL, and 0.8 ± 0.1 mL, respectively. CRT significantly attenuated AA irritation of the urinary bladder and exerted protective effects on basal pressure, micturition pressure, micturition interval, and micturition volume. Furthermore, CRT could prevent the excess blood flow and edematous change under the urothelium induced by intravesical AA instillation. No obvious changes in immunohistochemical HIF1α staining were observed among the groups. CRT attenuated DO induced by intravesical AA instillation in a rat experimental model. CRT might impart therapeutic effects on OAB via the mitigation of urothelial damage and regulation of excess blood flow.

Giant Invasive Sacral Schwannoma with Aortic Bifurcation Compression and Hydronephrosis.

BACKGROUND: Sacral schwannomas are rare tumors arising from nerve sheath Schwann cells. They are classified into 3 types: first type schwannoma arising from the sacrum, second type schwannoma eroding the sacrum, and third type schwannoma extending extensively, involving anterior, posterior, and retroperitoneal space. Among these type 2 sacral tumors, according to Klimo's classification, an eroding sacrum extending all over posteriorly, anteriorly, and laterally is still rarer. Only 38 cases have been reported in literature reviews. Only 6 cases of giant tumors of >10 cm in any 1 dimension have been reported. CASE DESCRIPTION: We present such a giant sacral schwannoma, with invasiveness eroding the sacrum; compressing the ureters, aortic bifurcation, bladder, and bowel; and presenting as lower abdominal pain, hydronephrosis, dysuria, and constipation. This is the first case reported in the literature that has described a large retroperitoneal tumor compressing retroperitoneal structures-aortic bifurcation vascular compression and ureter compression causing hydronephrosis. CONCLUSIONS: Though complete resection, which caused various severe postoperative complications in the reported cases, is the best option, a less morbid procedure would be appropriate; hence we underwent subtotal excision of the tumor, with complete recovery of our patient's symptoms without neurologic deficit.

Nicotine-induced hypoxia in rat urothelium deteriorates bladder storage functions.

AIMS: To measure the effects of nicotine on lower urinary tract symptoms (LUTS), bladder blood flow, and the urothelial markers hypoxia-inducible factor 1α (HIF1α), uroplakin III (UPIII), and aquaporin 3 (AQP3). METHODS: Ten-week-old female Sprague Dawley rats were subcutaneously injected with 2 mg/kg nicotine (n = 17) or vehicle (control, n = 18) twice daily for 13 days. Some nicotine-treated rats (n = 10) were injected daily with 1 mg/kg tadalafil for the last 6 days of nicotine treatment. One day before cystometry, the bladders of some nicotine-treated and control rats were instilled with 0.08% acetic acid. Urinary frequency and volume were measured 1 day after treatment. Blood flow in the bladder neck was measured, and the urothelia were immunochemically assayed for HIF1α, UPIII, and AQP3. RESULTS: Following acetic acid treatment, both voiding interval and micturition volume of the nicotine-treated rats were significantly lower than controls. Nicotine-treated rats had lower blood flow than controls, and the urothelial expression of HIF1α was higher than controls. Simultaneously, the expressions of UPIII and AQP3 were decreased. Tadalafil treatment increased bladder blood flow, and nicotine-treated rats had increased voiding interval and micturition volume. Further, the expression of HIF1α decreased, and both UPIII and AQP3 levels increased. CONCLUSIONS: Nicotine-treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. Changes in tissue markers in the nicotine-treated rats were consistent with hypoxia and loss of urothelial function. Restoration of blood flow reversed the nicotine effects. Nicotine may induce LUTS through reduced bladder blood flow and urothelial hypoxia.

Reduced transient receptor potential vanilloid 2 expression in alveolar macrophages causes COPD in mice through impaired phagocytic activity.

BACKGROUND: Defective phagocytosis in alveolar macrophages is associated with chronic obstructive pulmonary disease (COPD). Transient receptor potential cation channel subfamily V member 2 (TRPV2), a type of nonselective cation channel pertinent to diverse physiological functions, regulates macrophage phagocytosis. However, the role of TRPV2 in COPD remains poorly understood. Here, we explored the role of TRPV2 in the development of COPD. METHODS: Macrophage TRPV2 expression and phagocytosis function were measured in MH-S cells (a murine alveolar macrophage cell line) and a cigarette smoke exposure mouse model. RESULTS: TRPV2 expression and phagocytosis function were reduced when MH-S cells were exposed to cigarette smoke extract (CSE). TRPV2 knockdown by siRNA decreased phagocytosis in MH-S cells. Consistently, TRPV2 expression was reduced in alveolar macrophages prepared from bronchoalveolar lavage samples of mice which were exposed to cigarette smoke for 2 months. In addition, the alveolar space was progressively enlarged during development in TRPV2 knockout (TRPV2KO) mice. Moreover, exposure to cigarette smoke for 2 months significantly induced alveolar space enlargement in TRPV2KO mice, but not in wild-type (WT) mice. The phagocytic function of alveolar macrophages from TRPV2KO mice was reduced, compared with macrophages from WT mice. CONCLUSIONS: TRPV2 expression is profoundly downregulated in alveolar macrophages at early time points of cigarette smoke exposure. Reduced TRPV2-mediated phagocytic function renders the lung susceptible to cigarette smoke-induced alveolar space enlargement. TRPV2 may provide a therapeutic target for COPD induced by cigarette smoke.

[EFFECTIVENESS OF HOCHUEKKITO (JAPANESE HERBAL MEDICINE) FOR GENERAL FATIGUE AFTER INTRODUCTION OF ENZALUTAMIDE IN THREE CASES OF CASTRATION-RESISTANT PROSTATE CANCER].

(Purpose) Enzalutamide is one of the therapeutic options for castration-resistant prostate cancer (CRPC). However, general fatigue is frequently observed in patients after introduction of enzalutamide. Here, we used the Cancer Fatigue Scale (CFS) to monitor general fatigue after introduction of enzalutamide, and administered the Japanese herbal medicine (Kampo) drug, Hochuekkito, for management of general fatigue. (Materials and methods) Three patients with CRPC were enrolled in this retrospective observational study. The patients were all male, 72, 69, and 88 years old, respectively, and had received previous hormone therapy for CRPC. They complained of general fatigue 2-5 weeks after introduction of enzalutamide. The CFS was divided into three subcategories: physical fatigue, affective fatigue, and cognitive fatigue. Hochuekkito was prescribed for management of general fatigue. Moreover, 31 previous CRPC cases treated in our hospital were divided into a general fatigue group and a non-general fatigue group. The period of enzalutamide prescription was compared among the previous groups and the present three cases to determine the usefulness of Hochuekkito. (Results) In this series, CFS was useful to monitor general fatigue after introduction of enzalutamide. General fatigue after introduction of enzalutamide mainly consisted of physical fatigue, and improved in two of the three cases included in this study. However, enzalutamide was discontinued in one patient due to general fatigue. Fourteen of our 31 previous CRPC cases developed general fatigue after introduction of enzalutamide. The mean periods of enzalutamide prescription were 265.6, 173.2, and 193.0 days in the non-general fatigue, general fatigue, and the present three cases, respectively. The differences among the groups were not significant. (Conclusions) The CFS is useful to monitor general fatigue, including its subcategories, after introduction of enzalutamide in patients with CRPC. The Kampo medicine Hochuekkito may be useful for management of general fatigue in such cases.

[Investigation of Repeatability of Residual Urine Volume Measurement for Lower Urinary Tract Disorder in Patients with Lumbar Degenerative Disorders].

STUDY DESIGN: prospective study OBJECTIVE:To evaluate repeatability of residual urine(RU)volume measurement(RUM)in patients with lumbar degenerative disorders. SUMMARY OF BACKGROUND DATA: RUM by abdominal echo is a non-invasive modality to evaluate lower urinary tract disorder(LUTD), repeatability of which is not found in urological disorders. Additionally, its repeatability has not been confirmed in spinal disorders. The authors examined repeatability of RUM for evaluation of LUTD in patients with lumbar degenerative disorders. METHODS: Thirty-four patients with lumbar degenerative disorders and 7 normal adult volunteers entered our study. RUM was performed at least twice(two to seven times; average 3.6 times). According to urological guidelines, RU over 50 cc is defined as abnormal. Thirty-four patients were divided into two groups:the U+group with lower urinary tract lesion(16 patients)and the U-group without such a lesion(18 patients). RESULTS: In normal adult volunteers:In all volunteers, there was no abnormal RU. Repeatability of RUM was 100%. Average RU volume was 1.6 cc. In patients with lumbar degenerative disorders:Repeatability of RUM was 94.4% in the U-group(average RU volume was 35.2 cc)and 50% in the U+group(average RU volume was 50.1 cc). In all patients with lumbar degenerative disorders, repeatability of RUM was 73.5%(average RU volume was 43.0 cc). CONCLUSIONS: Repeatability of RUM in patients with lumbar degenerative disorders was 73.5%. Especially, in patients without lower urinary tract lesion, high repeatability of RUM was confirmed. According to the present study, RUM seemed to be a dependable modality to evaluate LUTD in patients with lumbar degenerative disorders.

A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models.

Emphysema is a typical component of chronic obstructive pulmonary disease (COPD), a progressive and inflammatory airway disease. However, no effective treatment currently exists. Here, we show that keratan sulfate (KS), one of the major glycosaminoglycans produced in the small airway, decreased in lungs of cigarette smoke-exposed mice. To confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 ([SO3--6]Galß1-4[SO3--6]GlcNAc) was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. Histological and microcomputed tomography analyses revealed that, in the mouse elastase-induced emphysema model, administration of L4 attenuated alveolar destruction. Treatment with L4 significantly reduced neutrophil influx, as well as the levels of inflammatory cytokines, tissue-degrading enzymes (matrix metalloproteinases), and myeloperoxidase in bronchoalveolar lavage fluid, suggesting that L4 suppressed inflammation in the lung. L4 consistently blocked the chemotactic migration of neutrophils in vitro. Moreover, in the case of the exacerbation model, L4 inhibited inflammatory cell accumulation to the same extent as that of dexamethasone. Taken together, L4 represents one of the potential glycan-based drugs for the treatment of COPD through its inhibitory action against inflammation.

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

Effect of nitrate on nodule and root growth of soybean (Glycine max (L.) Merr.).

The application of combined nitrogen, especially nitrate, to soybean plants is known to strongly inhibit nodule formation, growth and nitrogen fixation. In the present study, we measured the effects of supplying 5 mM nitrate on the growth of nodules, primary root, and lateral roots under light at 28 °C or dark at 18 °C conditions. Photographs of the nodulated roots were periodically taken by a digital camera at 1-h intervals, and the size of the nodules was measured with newly developed computer software. Nodule growth was depressed approximately 7 h after the addition of nitrate under light conditions. The nodule growth rate under dark conditions was almost half that under light conditions, and nodule growth was further suppressed by the addition of 5 mM nitrate. Similar results were observed for the extending growth rate of the primary root as those for nodule growth supplied with 5 mM nitrate under light/dark conditions. In contrast, the growth of lateral roots was promoted by the addition of 5 mM nitrate. The 2D-PAGE profiles of nodule protein showed similar patterns between the 0 and 5 mM nitrate treatments, which suggested that metabolic integrity may be maintained with the 5 mM nitrate treatment. Further studies are required to confirm whether light or temperature condition may give the primary effect on the growth of nodules and roots.

[Evaluation of micturitional disturbance in spinal disorders: reproducibility of uroflowmetry].

Patients with spinal degenerative diseases suffer not only neuropathy in the extremities but also lower urinary tract dysfunction(LUTD). Patients with cauda equina syndrome generally need emergency decompression to pelvic visceral function, especially that of the urinary bladder. However, less prominent voiding symptoms can be missed in clinical settings. There is a discrepancy between lower urinary tract symptoms and LUTD. Therefore, urodynamic studies are needed to screen of patients with spinal diseases. Cystometry and urethral sphincter electromyography are useful for increasing our understanding of LUTD but are too invasive for screening. Our protocol for the evaluation of LUTD consists of residual urine measurement and uroflowmetry(UFM). UFM is the simplest and noninvasive urodynamic technique;however, it has the disadvantage of being nonreproducible, which depends on bladder volume, diurnal variation, presence of obstructive disease, and mental stress. UFM was reportedly reproducible in normal individuals in 1979, but was not evaluated in patients with spinal disease. This study examined the reproducibility of UFM in patients with spinal disease. UFM was performed twice in 26 male patients with cervical or lumbar degenerative disease. Maximum urinary flow rate corrected with Siroky's nomogram was reproducible in 23(88.5%)of the 26 patients. A urinary flow curve was reproducible in 25(96.2%)of the 26 patients, and only 1 patient had excessive urination at the 1st UFM and normal urination at the 2nd UFM. The reproducibility of UFM was high in patients with spinal degenerative disease.

Efficacy and safety of advanced renal cell carcinoma patients treated with sorafenib: roles of cytokine pretreatment.

BACKGROUND: We conducted a retrospective, questionnaire-based analysis to assess the outcomes of advanced renal cell carcinoma (RCC) in Japanese patients treated with sorafenib in the daily clinical setting. PATIENTS AND METHODS: Patients (n = 110) were treated with sorafenib 400 mg twice daily at 12 centers. Overall survival (OS), progression-free survival (PFS), safety, and prognostic factors associated with PFS were assessed. RESULTS: The median OS was not reached within the study period, while the median PFS was 11.0 mo [95 % confidence interval (CI), 6.6 to 14.4 mo]. Univariate analysis showed that higher C-reactive protein (CRP) level, lower Na(+) level, and presence of liver metastasis were significant predictors of poorer PFS (p < 0.05, respectively). Among these variables, multivariate analysis identified higher CRP level (p = 0.004) and the presence of liver metastasis (p < 0.001) as being significantly associated with poorer PFS. The most common adverse event was skin toxicity (67 %), followed by gastrointestinal symptoms (26 %), hypertension (22 %), fatigue (19 %), hematological toxicity (10 %), and hemorrhage (6 %). The incidence of adverse events was comparable to that of previously reported clinical trials. CONCLUSIONS: Multivariate analysis indicated that CRP and liver metastasis were negatively associated with prognosis. Sorafenib therapy for Japanese patients with advanced RCC was effective and well tolerated.

Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice.

Despite the established role of alveolar type II epithelial cells for the maintenance of pulmonary function, little is known about the deregulation of lipid composition in the pathogenesis of pulmonary fibrosis. The elongation of long-chain fatty acids family member 6 (Elovl6) is a rate-limiting enzyme catalysing the elongation of saturated and monounsaturated fatty acids. Here we show that Elovl6 expression is significantly downregulated after an intratracheal instillation of bleomycin (BLM) and in human lung with idiopathic pulmonary fibrosis. Elovl6-deficient (Elovl6⁻/⁻) mice treated with BLM exhibit severe fibroproliferative response and derangement of fatty acid profile compared with wild-type mice. Furthermore, Elovl6 knockdown induces a change in fatty acid composition similar to that in Elovl6⁻/⁻ mice, resulting in induction of apoptosis, TGF-ß1 expression and reactive oxygen species generation. Our findings demonstrate a previously unappreciated role for Elovl6 in the regulation of lung homeostasis, and in pathogenesis and exacerbation of BLM-induced pulmonary fibrosis.