22 research outputs found
Pathological analysis of spermatic dysfunction following testicular ischemia-reperfusion injury\n
Introduction & Objectives: Torsion, which may result in testicular ischemia, requires emergency surgery to restore testicular blood flow. However, the risk of spermatic dysfunction remains even if surgery is performed. The pathology of spermatic dysfunction in testicular ischemia-reperfusion injury (TIRI) remains unclear. A previous study showed the relevance of inflammation and oxidative stress in the other organs of ischemia-reperfusion injury. We hypothesized that inflammation and oxidative stress play key roles in causing spermatic dysfunction following TIRI. We investigated the pathophysiology of spermatic dysfunction in TIRI focusing on inflammatory changes using TIRI model mice. Materials and Methods: The study used C57BL/6J male mice aged 10 to 15 weeks. To create TIRI model mice, the unilateral (left side) testicular vessels were clamped using Dieffenbach clamps (Bulldog clamps) for 1 hour and de-clamped. The bilateral testes were removed at 0 (ischemic state), 1, 3, and 5 weeks after creating the TIRI model mice. Spermatic changes following TIRI were investigated by analyzing the histology of the testes and semen and assessing levels of inflammation and oxidative stress. Semen was collected from the bilateral cauda epididymites and investigated using the sperm motility analysis system (SMAS). Results: Histological analysis after hematoxylin-eosin staining showed tissue thickening in interstitial tissues at week 1 and 3 on the left (affected) testis, and week 1, 3 and 5 on the right (unaffected) testis. The infiltration of lymphocytes-predominant inflammatory cells were observed at week 1 and week 3 on the left (affected) testis. The destruction of ductal structures and giant cells were observed at weeks 3 and 5 on the left (affected) testis and week 5 on the right (unaffected) testis. SMAS showed significantly decreased spermatic concentration and motility in both testes of TIRI model mice compared with those of sham-operated mice at weeks 1, 3 and 5. Inflammation analysis using an inflammation-related proteome assay showed significantly increased levels of cytokines (IL-2, IL-3, IL-17A, and IL-23) and chemokines (CCL2, CCL5, CXCL1, and CX3CL1) at weeks 1, 3, and 5 in both testes of TIRI model mice. For the assessment of oxidative stress, enzyme-linked immuno-sorbent assay (ELISA) for 8-hydroxy-2’-deoxyguanosine (8-OHdG) was performed, which showed that levels of 8-OHdG were significantly increased in the left (affected) testis of TIRI model mice compared with that of sham-operated mice at all observation periods. Meanwhile, ELISA showed that levels of 8-OHdG in the right (unaffected) testis were significantly increased in TIRI model mice at weeks 3 and 5 compared with that of sham-operated mice. Conclusions: Spermatic dysfunction following TIRI is induced by inflammation and oxidative stress. Inflammation and oxidative stress may be novel regulatory factors to prevent spermatic dysfunction following TIRI
Preventive effect of indoleamine 2,3-dioxygenase 1 inhibition on lipopolysaccharide-induced prostatitis
Introduction and Objectives: Bacterial infections are the main cause of acute prostatitis and are treated with appropriate antimicrobial therapy. However, approximately 5% of patients continue to have inflammatory symptoms even after receiving antibacterial therapy, leading to refractory conditions. Bacterial prostatitis requires additional therapy, focusing on inflammatory changes. Indoleamine 2,3-dioxygenase 1 (IDO1) catalysis is the first rate-limiting step of tryptophan metabolism. IDO1 is expressed in the prostate and plays a key role in the immune response. As the first step in investigating the relationship between acute prostatitis and IDO1, we investigated the preventive effect of IDO1 inhibition on lipopolysaccharide (LPS)- induced prostatitis using IDO knockout (Ido1 −/−) mice in this study. Materials and Methods: The study used Ido1 −/− and wild-type (Ido1 +/+) C57BL/6J malemice aged 10–15 weeks. LPS Escherichia coli O26 (100μg/PBS, 100μL) was administered transurethrally into the lower urinary tract to create a mouse model of LPS-induced prostatitis. The prostates were removed 1, 3, 5, and 7 days after creating the model mice. Histological, immunohistochemical, and biochemical analyses were used to compare the preventive effect in Ido1 −/− mice compared with that in Ido1+/+ mice. Results: HE staining showed suppression of ductal destruction following infiltration of inflammatory cells in Ido1 −/− mice compared with Ido1 +/+ mice. The enzyme-linked immunosorbent assay (ELISA) method was used for kynurenine pathway analysis, which showed significantly maintained tryptophan levels and decreased L-kynurenine levels in Ido1 −/− mice compared to Ido1 +/+ mice. The IDO1 assay in Ido1 +/+ mice showed significantly increased levels during all observation periods after creating the model compared with that under normal conditions. Immunofluorescent staining using five types of cytokines and chemokines (IL-2, IL-4, IL-17, CCL2, and CCL3) related to the pathophysiology of acute prostatitis showed decreased expression of these cytokines and chemokines in Ido1 -/- mice compared with Ido1 +/+ mice. Inflammation-related proteome assays showed decreased levels of IL-1β, IL-4, IL-5, IL-6, IL-17, CCL2, CCL3, CXCL1, CXCL11, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 in Ido1 −/− mice compared with Ido1 −/− mice during all observation periods after model creation. Conclusions: IDO1 is involved in LPS-induced prostatitis through cytokines and chemokines. IDO1 inhibition contributes to the prevention of LPS-induced prostatitis. IDO1 inhibition has the potential to serve as an additional therapy for acute prostatitis
Pathophysiological analysis of detrusor overactivity following partial bladder outlet obstruction
Introduction: Detrusor overactivity (DO) following partial bladder outlet obstruction (PBOO) is a common urological condition in humans, with 50-70% patients with PBOO complicated with DO. The pathological mechanisms of DO following PBOO are largely unknown, but inflammatory changes may play a key role. We hypothesized that inflammation is important in the earlier pathophysiological phase before overproduction of oxidative stress in DO following PBOO. Therefore, we investigated the relationships among bladder function, ischemia, oxidative stress and inflammation in DO following PBOO in PBOO model mice. Materials and Methods: C57BL/6J male mice aged 10 to 15 weeks were used in the study. PBOO model mice were created surgically by ligation of the proximal urethra with 5-0 nylon suture under inhalation anesthesia. Sham-operated mice were used as controls. Pathophysiological changes in the bladder at 1, 3 and 5 weeks after creation of the PBOO model mice were compared with those in sham-operated mice using functional, histological, biochemical and immunohistochemical analyses. Results: Functional analysis using a pressure flow study showed increased maximum detrusor pressure at 1 week and DO from 3 to 5 weeks after creation of the PBOO model. Histological analysis using hematoxylin-eosin and Masson-Trichrome staining showed greater invasion of inflammatory cells and fibrosis in PBOO model mice compared with sham-operated mice at 3 and 5 weeks. Inflammatory cells were mainly present in interstitial tissue, and fibrosis gradually infiltrated from interstitial tissue to the muscular layer. Ischemia analysis showed significantlyincreased HIF-1α in PBOO model mice at all time points. Oxidative stress analysis indicated significantly increased levels of ROS from 1 week and 8-OHdG from 3weeks in PBOO model mice. An inflammation-related proteome assay showed high levels of colony stimulating factor (CSF) family proteins at 1 week and IL-2, IL-3, IL-17A, IL-23, MMP-3, MMP-9 and periostin from 3 to 5 weeks in PBOO model mice. Conclusions: Oxidative stress and inflammatory changes showed contemporaneous increase in pathophysiology of detrusor overactivity following partial bladder outlet obstruction. Especially, CSF family and ROS changes are showed in the early stage, and might be a predict marker in the pathophysiology of DO following PBOO at the early stage
Pathological analysis of spermatic dysfunction following testicular ischemia-reperfusion injury\n
Regular Articlejournal articl
Preventive effect of indoleamine 2,3-dioxygenase 1 inhibition on lipopolysaccharide-induced prostatitis
Regular Articlejournal articl
Pathophysiological analysis of detrusor overactivity following partial bladder outlet obstruction
Regular Articlejournal articl
多菌種バイオフィルムモデルにて示された、第四級アンモニウム塩を含有する新規シランカップリング剤の抗菌活性
新規な第四級アンモニウムシランカップリング剤であるヨウ化N-アリル-N-デシル-N-メチル-N-トリメトキシシリルプロピルアンモニウム(10-I)が多菌種バイオフィルムモデルに対して発揮する抗菌活性を調べる実験を施行した。上記モデルにおけるバイオフィルム形成初期を実験系に用いることで、口腔内プラーク様のバイオフィルムが固相表面に形成される状況を模倣させた。カバーグラスを濃度800ppmの10-I溶液に1時間浸漬して表面修飾処理を行い、上記のバイオフィルムを形成させた。コロニー形成単位(CFU)を計数した結果、10-I処理を行った群では対照群に対してCFUが80%減少したことから、10-Iが強い抗菌活性を有することが実証された。10-Iによる表面修飾処理は、常在菌に関連する歯科疾患のみならず誤嚥性肺炎などの全身合併症を予防低減する効果的な方法となることが当結果から示唆された。新規な第四級アンモニウムシランカップリング剤であるヨウ化N-アリル-N-デシル-N-メチル-N-トリメトキシシリルプロピルアンモニウム(10-I)が多菌種バイオフィルムモデルに対して発揮する抗菌活性を調べる実験を施行した。上記モデルにおけるバイオフィルム形成初期を実験系に用いることで、口腔内プラーク様のバイオフィルムが固相表面に形成される状況を模倣させた。カバーグラスを濃度800ppmの10-I溶液に1時間浸漬して表面修飾処理を行い、上記のバイオフィルムを形成させた。コロニー形成単位(CFU)を計数した結果、10-I処理を行った群では対照群に対してCFUが80%減少したことから、10-Iが強い抗菌活性を有することが実証された。10-Iによる表面修飾処理は、常在菌に関連する歯科疾患のみならず誤嚥性肺炎などの全身合併症を予防低減する効果的な方法となることが当結果から示唆された