Association between chronic prostatitis and the subsequent benign prostatic hyperplasia: a population-based national cohort study.

PURPOSE: To explore the association between chronic prostatitis (CP) and the subsequent development of benign prostatic hyperplasia (BPH). METHODS: Data analyzed were medical claims of Taiwan's National Health Insurance program. From 2010 to 2017, 3571 patients ≧20 years with CP diagnosed by certified urologists were enrolled. Patients with past BPH diagnosis and diagnosis of prostate cancer, inguinal hernia, interstitial cystitis, and urethritis in the past and within one year after the first CP diagnosis were excluded. Age-matched controls were randomly selected from all non-CP individuals of the same exclusion criteria in the study period with a CP/non-CP ratio of 1:4. The follow-up was made from the first CP diagnosis to death or the end of 2018. The endpoint was the newly diagnosed BPH. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of BPH in association with CP. RESULTS: Over a maximum of 8 years of follow-up, 287 (8.03%) and 258 (0.43%) BPH events were noted for the CP and non-CP group, respectively, representing a covariate adjusted HR (aHR) of 4.30 (95% CI, 3.61-5.13). Younger patients tended to suffer from higher aHRs, especially those aged 20-39 years (aHR: 11.45, 95% CI, 5.12-25.64). CONCLUSION: The Taiwan national health database indicated that CP patients had a significantly higher risk of developing BPH later than non-CP patients. Interestingly, the younger the CP is diagnosed (under 40), the greater the risk.

The sufficient multidisciplinary specialists under a government-led health care system associated with the downward mortality trend of Fournier's gangrene in Taiwan.

OBJECTIVES: To explore the trends in Fournier's gangrene (FG) incidence and mortality rate in Taiwan and to investigate the contributing factors to such changes. METHODS: Between 2002 and 2016, hospitalized FG patients who underwent subsequent surgical intervention were included in this retrospective study. Incidence, outcomes, age-adjusted Charlson Comorbidity Index (ACCI), hospitalization cost, surgical timing, and the number of multidisciplinary specialists involved in the first-line management of FG in each year were collected. Simple linear regression and Pearson correlation coefficient (r) were used for the subsequent analysis. RESULTS: The national cohort enrolled 2183 FG patients from 2002 to 2016 in Taiwan. The age-standardized incidence rate of FG was between 0.4 and 0.8 per 100 000 population, and overall mortality was 7.8% in these 15 years. We illustrated the downward trendline of FG mortality with a 0.62 coefficient of determination. The mortality of FG patients who underwent surgery within 24 h and after 24 h were found to be 8.3 ± 3.9% and 14.6 ± 25.2%, respectively (p = 0.02). The numbers of urologists, anesthesiologists, emergency doctors, and physicians per 100 000 population had a strong negative linear correlation with FG mortality (r = 0.8, p < 0.001). ACCI score had a moderate linear relationship with FG mortality (r = 0.57, p = 0.027). The hospitalization cost showed a weak linear correlation with FG mortality (r = -0.03, p = 0.92). CONCLUSIONS: We demonstrated the downward trend of the FG mortality rate in Taiwan from 2002 to 2016. Besides underlying comorbidities and surgical timing, sufficient multidisciplinary specialists are essential for the survival benefit of FG patients in Taiwan experience.

MicroRNA-145-5p modulates Krüppel-like factor 5 and inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma.

BACKGROUND: In several human cancers, Krüppel-like factor 5 (KLF5), a zinc finger transcription factor, can contribute to both tumor progression or suppression; however, the precise role of KLF5 in nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, the association between KLF5 and microRNA-145-5p (miR-145-5p) in NPC cells was elucidated. RESULTS: Our results showed that KLF5 expression was up-regulated in NPC group compared to normal group. We found that KLF5 exhibited an oncogenic role in NPC cells. The upregulation of miR-145-5p inhibited the proliferation, migration, and invasion of NPC cells. It was observed that miR-145-5p could down-regulate the mRNA and protein expression of KLF5 in NPC cell lines. Additionally, the activity of focal adhesion kinase (FAK), a migration marker, was regulated by miR-145-5p and KLF5 in NPC cells. CONCLUSIONS: The results of this study indicated that miR-145-5p could repress the proliferation, migration, and invasion of NPC cells via KLF5/FAK regulation, and could be a potential therapeutic target for patients with NPC.

Induction of apoptosis in prostate cancer by ginsenoside Rh2.

The therapeutic action of ginsenoside Rh2 on several cancer models has been reported. This study aimed to evaluate its apoptotic effect on prostate cancer and the underlying mechanism. Cultured DU145 cells were treated with Rh2 (5 × 10-5 to 1 × 10-4 M), peroxisome proliferator-activated receptor-delta (PPAR-delta) antagonist GSK0660 (1 × 10-6 to 5 × 10-6 M); or small interfering RNA (siRNA) of PPAR-delta. The treatment effects were evaluated with cell viability assay, life/death staining and flow cytometry for apoptosis. Immunostaining was used for reactive oxygen species (ROS) and superoxide detection. Western blot analysis for PPAR-delta and signal transducer and activator of transcription 3 (STAT3) protein expression were performed. The results showed that Rh2 significantly decreased DU145 cell survival and increased cell apoptosis. ROS and superoxide induction, PPAR-delta up-regulation and phosphorylated STAT3 (p-STAT3) down-regulation by Rh2 were demonstrated. GSK0660 partially but significantly inhibited the Rh2-induced apoptosis and restored cell viability. Treatment with siRNA reversed the Rh2-induced apoptosis as well as changes in PPAR-delta and p-STAT3 expression. In conclusion, our findings have demonstrated that ginsenoside Rh2 induces prostate cancer DU145 cells apoptosis through up-regulation of PPAR-delta expression which is associated with p-STAT3 up-regulation and ROS/superoxide induction. Rh2 may be potentially useful in the treatment of prostate cancer.

Emphysematous cholecystitis presenting as gas-forming liver abscess and pneumoperitoneum in a dialysis patient: a case report and review of the literature.

BACKGROUND: Emphysematous cholecystitis is a rare variant of acute cholecystitis with a high mortality rate. The combination of emphysematous cholecystitis, liver abscess and pneumoperitoneum are even rarer. Herein we present a case of emphysematous cholecystitis in a senile diabetic lady who had worsening hemodynamics while undergoing hemodialysis. CASE PRESENTATION: A 64-year-old woman with history of type 2 diabetes mellitus and end stage renal disease with regular hemodialysis presented to the emergency department with a 1-day history of sudden onset of lassitude and hypotension during hemodialysis. The result of a computed tomography (CT)-scan revealed air encircling the gallbladder, liver parenchymal and minimal pneumoperitoneal and liver abscess with no cholelithiasis. The patient had received empirical antibiotics with piperacillin-tazobactam 2.25 g intravenous route every 6 h for 14 days and cholecystectomy with surgical debridement and lead an uneventful postoperative hospital course. Escherichia coli was demonstrated as well as blood culture and peritoneal fluid culture. CONCLUSION: In a senile diabetic and dialysis patient, we should take emphysematous cholecystitis into consideration once vague abdominal pain occurrs. Empirical antibiotic therapy and adequate surgical intervention should take place as soon as possible.

Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma.

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

Urinary Bladder Relaxation through Activation of Imidazoline Receptors Induced by Agmatine is Increased in Diabetic Rats.

OBJECTIVES: The effect of agmatine on bladder contractility and the diabetes-induced alteration of this action were studied in the rat. METHODS: Bladder strips were isolated from 9-week-old streptozotocin (STZ)-diabetic rats and control Wistar rats. Strips were hung in an organ bath for measurement of isometric tension and pre-contracted with either 1 µmol/L acetylcholine (ACh) or 50 mmol/L KCl. Dose-dependent relaxation of the bladder strips was studied by cumulative administration of agmatine 1-100 µmol/L into the organ bath. Effects of specific imidazoline receptor (IR) antagonists on the agmatine-induced relaxation were studied. Western blotting analysis was used to measure bladder IR, sulphonylurea receptor (SUR) and inwardly rectifying K(+) channel subunit 6.2 (Kir 6.2) protein levels. RESULTS: Agmatine reduced ACh and KCl pre-contracted bladder strip tension in a dose-dependent fashion. Relaxation was significantly increased in STZ-diabetic rats. The relaxation was inhibited by BU224, a selective I2 IR antagonist; but not by efaroxan (I1 IR antagonist) or KU14R (I3 IR antagonist). Moreover, the agmatine-induced relaxation was attenuated by glibenclamide (inhibitor of KATP channel) and H-89 (inhibitor of protein kinase A), but enhanced by 3-isobutyl-1-methylxanthine (IBMX, inhibitor of cyclic AMP phosphodiesterase). Western blotting showed increased expression of bladder IR but not SUR or Kir 6.2 in the STZ-diabetic rat. CONCLUSION: Agmatine causes rat bladder relaxation by activation of the I2 IR, which opens KATP channels through the cyclic AMP/protein kinase A pathway. Agmatine-induced bladder relaxation in STZ-diabetic rats is increased due to a higher expression of IR.

Agmatine Induces Rat Prostate Relaxation through Activation of Peripheral Imidazoline I2 -Receptors.

OBJECTIVES: The effect of agmatine on prostate contractility as well as the roles of imidazoline receptors and potassium channels in this action were studied using isolated Wistar rat prostate tissue. METHODS: Rat prostate strips were pre-contracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. The relaxation response to agmatine (1-100 µmol/L) was measured. The effects of imidazoline receptor blockers: efaroxan, BU224, KU14R; ATP-sensitive K(+) channels (KATP ) channel inhibitor: glibenclamide; cyclic AMP (cAMP) phosphodiesterase inhibitor: IBMX; or protein kinase A (PKA) inhibitor: H-89 on the agmatine-induced relaxation were studied. RESULTS: Agmatine produced relaxation in prostate strips pre-contracted with phenylephrine or KCl in a dose-dependent manner. This relaxation was significantly reduced by BU224, a selective I2 imidazoline receptor (IR) blocker, but not by I1 or I3 IR blockers (efaroxan, KU14R respectively). Moreover, the agmatine-induced relaxation was attenuated by glibenclamide and H-89, but enhanced by IBMX. CONCLUSION: The results suggest that agmatine causes rat prostate relaxation by activation of the I2 IR, which opens KATP channels through cAMP/PKA pathway.

Metabolic syndrome decreases tissue perfusion and induces glandular hyperplasia in the fructose-fed rat prostate.

AIMS: The effects of metabolic syndrome on the prostate blood perfusion and histological structure were studied using fructose-fed rats (FR). METHODS: Age-matched male Wistar rats were divided into two groups: group I, normal control rats and group II, 9-week FR. Animal body weight, blood pressure, and serum metabolic parameters were monitored. With the rats under anesthesia, prostatic blood flow volume and flow velocity were measured by laser Doppler flowmetry. The prostate was then removed for histological examination and morphometric study. RESULTS: The 9-week FR showed significant increases in body weight, blood pressure, plasma glucose, insulin, and triglyceride levels. The blood flow volume (345.8 ± 20.57 ml/min/100 g vs. 440.4 ± 35.57 ml/min/100 g of tissue, P < 0.05 for n = 8) and flow rate (29.4 ± 1.25 units vs. 40.9 ± 2.65 units, P < 0.05 for n = 8) in the FR ventral prostate were significantly decreased when compared to controls. Structurally, the FR prostate weight was significantly higher than that of the controls (612.4 ± 16.9 mg vs. 427.3 ± 6.5 mg, P < 0.05 for n = 8). Prostate histology showed glandular hyperplasia while morphometry showed increased stromal component in the FR. CONCLUSIONS: Metabolic syndrome in the FR decreases prostatic perfusion and induces prostatic glandular hyperplasia. The findings suggest that chronic ischemia may be a link between metabolic syndrome and prostatic enlargement.

Correlations among cardiovascular risk factors, prostate blood flow, and prostate volume in patients with clinical benign prostatic hyperplasia.

OBJECTIVE: To investigate the relationships among the cardiovascular risk factors, prostate blood flow, and prostate volume in patients with clinical benign prostatic hyperplasia (BPH). METHODS: A total of 130 patients with the clinical diagnosis of BPH were recruited. The presence of 5 cardiovascular risk factors, including obesity, diabetes, hypertension, hyperlipidemia, and a history of cardiovascular events, was recorded. The urologic evaluation included digital rectal examination, serum prostate-specific antigen, International Prostate Symptom Score, and transrectal ultrasonography. Doppler spectrum analysis was performed with the patient in the right lateral decubitus position to measure the blood flow in the prostate capsular arteries, periurethral arteries, and neurovascular bundles. The correlations were analyzed between the resistive indexes of the prostatic branches and the cardiovascular risk factors, as well as the transrectal ultrasound findings. RESULTS: The resistive indexes of the periurethral arteries and right neurovascular bundles showed positive correlations with the number of cardiovascular risk factors in the patients (r=.228, P=.01 and r=.225, P=.011, respectively). The periurethral artery resistive index also correlated positively with both prostate and transitional zone volumes, with the capsular artery correlating positively only with the latter. No significant correlations were noted between the resistive indexes and the International Prostate Symptom Score. CONCLUSION: Prostate vascular resistance in patients with BPH has positive correlations with cardiovascular risk factors and prostate size. These findings suggest that prostate hypoxia might play a role in the pathogenesis of BPH.

Loperamide-induced rat prostate relaxation through activation of peripheral µ-opioid receptors.

AIMS: The effect of µ-opioid receptor (MOR) agonist, loperamide on prostate relaxation and the role of potassium channel in this action were studied in isolated Wistar rat prostate. METHODS: Tissue strips from rat prostate ventral lobe were hung in organ bath containing: group 1: standard Tyrode's solution (TS); group 2: TS with 1 µM naloxone; group 3: TS with 0.1 µM naloxonazine; and group 4: TS with 0.01-1 µM glybenclamide. The strips were pre-contracted with either 50 mM KCl or 1 µM phenylephrine. Dose-response study on the prostate strip was performed by cumulative administration of loperamide 0.1-10 µM into the organ bath. Western blot study was performed to detect the presence of MOR protein and adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP) ) subunit Kir6.2 protein expressions in the prostate tissue. RESULTS: Loperamide induced relaxation of the pre-contracted prostate strips in a dose-dependent fashion. Pre-treatment with 1 µM naloxone significantly inhibited the relaxation, thus suggesting activation of MOR in the loperamide effect. Pre-treatment with 0.1 µM naloxonazine inhibited relaxation only in the phenylephrine-contracted strips. The K(ATP) channel blocker glybenclamide significantly inhibited the loperamide-induced relaxation, indicating involvement of K(ATP) channels in mediating the prostate relaxation. Western blots showed the expression of MOR and Kir6.2 protein in the rat prostate. CONCLUSIONS: MOR and Kir6.2 are expressed in the rat prostate and loperamide induces rat prostate relaxation through activation of peripheral MOR. K(ATP) channels are involved in mediating the effect of loperamide on the relaxation of prostate.

Prompt plasmapheresis successfully rescue pulmonary-renal syndrome caused by ANCA-negative microscopic polyangiitis.

Pulmonary-renal syndrome (PRS) associated with antineutrophil cytoplasmic antibodies (ANCA)-negative microscopic polyangiitis (MPA) is relatively rare, and the effects of plasmapheresis on these patients remain unclear. Here, we report the case of a 66-year-old man who presented with fever, acute renal failure, thrombocytopenia, and sudden onset of diffuse pulmonary hemorrhage. Prompt plasmapheresis and concurrent pulse therapy with methylprednisolone effectively rescued his pulmonary-renal syndrome. The patient was then diagnosed with MPA on the basis of typical histological findings and the absence of surrogate markers of Wegener's granulomatosis and Churg-Strauss syndrome. This case demonstrates the therapeutic effects of plasmapheresis on ANCA-negative MPA and highlights the necessity of prompt plasmapheresis for not only resolving pulmonary hemorrhage but also increasing the likelihood of renal function restoration in patients with PRS.

Allopurinol-induced severe hypersensitivity with acute renal failure.

A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS). Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.