Potential Targets for Overactive Bladder in Older Men Based on Urinary Analysis of Metabolomics

2021 ◽  
pp. 1-7
Author(s):  
Satoru Kira ◽  
Tatsuya Miyamoto ◽  
Sachiko Tsuchiya ◽  
Hiroshi Nakagomi ◽  
Tatsuya Ihara ◽  
...  

<b><i>Objective:</i></b> We investigated the association between overactive bladder (OAB) and urinary metabolites in men. <b><i>Methods:</i></b> This prospective observational study included 42 men aged 65–80 years. The 3-day frequency volume chart (FVC), International Prostate Symptom Score (IPSS), and quality of life score were adapted to assess the micturition behavior. Participants with IPSS urgency score ≥2 were included in the OAB group, and those with IPSS urgency score &#x3c;2 were included in the control group. We performed a comprehensive metabolomic analysis using urine samples. Metabolites were compared between the groups using an unpaired <i>t</i> test and Fisher’s exact test in a nonadjusted analysis. Multivariable logistic regression analysis was performed to investigate the association between OAB and the metabolites. <b><i>Results:</i></b> Overall, 23 men were included in the OAB group and 19 in the control group. There were no differences in the background factors except age between the groups. FVC analysis demonstrated that nocturnal urine volume, 24-h micturition frequency, and nocturnal micturition frequency were significantly higher, and the maximum voided volume was significantly lower in the OAB group than in the controls. Metabolomic analysis revealed 14 metabolites that were differentially expressed between the groups. Multivariate analysis indicated that an increase in the levels of 5-iso prostaglandin F2α-VI (5-iPF2a-VI) and 5-methoxyindoleacetic acid was associated with OAB. <b><i>Conclusion:</i></b> Abnormal urinary metabolites, including metabolites in the tryptophan (5-methoxyindoleacetic acid, 3-indoleacetonitrile, and 3-hydroxyanthranilic acid) and arachidonic acid (5-iPF2a-VI) pathways, play a role in the pathogenesis of OAB in older men.

2019 ◽  
Vol 11 ◽  
pp. 175628721985008 ◽  
Author(s):  
Satoru Kira ◽  
Takahiko Mitsui ◽  
Tatsuya Miyamoto ◽  
Tatsuya Ihara ◽  
Hiroshi Nakagomi ◽  
...  

Background: Our aim was to investigate the association between serum metabolites and nocturia. Methods: A total of 66 males aged 65–80 years were enrolled in this study and stratified according to micturition behavior, which was characterized in terms of the 24 h frequency volume chart (FVC) for 3 consecutive days, the International Prostate Symptom Score (IPSS), and quality-of-life score. The nocturia group included participants with any total IPSS and ⩾1.5 micturitions/night as the mean of 3 nights, while the control group included participants with total IPSS < 8 and <1.5 micturitions/night. We conducted a comprehensive capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) study of plasma metabolites. Between-group comparisons of metabolite levels employed the Welch t test. The relationship between nocturia and metabolite profiles was determined using multivariable logistic regression analysis. Results: Of 66 participants, 45 were included in the nocturia group and 21 in the control group. There were no differences in background factors between the two groups. FVC analysis revealed that urine production during night-time, as well as micturition frequency during daytime and night-time were significantly higher in the nocturia group. CE-TOFMS identified eight metabolites whose plasma levels differed between the two groups. Multivariate analysis indicated that increased levels of lauric acid and imidazolelactic acid, as well as decreased levels of thiaproline and glycerol, contribute to the etiology of nocturia in aged men. Conclusions: Our findings suggest that abnormal serum levels of metabolites in several pathways play a role in the pathogenesis of nocturia in aged men.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hamid Arazi ◽  
Parvin Babaei ◽  
Makan Moghimi ◽  
Abbas Asadi

Abstract Background Regarding an important effects of physical exercise on brain function in elders, the aim of this study was to examine the effects of strength and endurance exercise on brain neurobiological factors in older men. Methods Thirty older men volunteered to participate in this study and were randomly assigned to strength, endurance and control groups. The subjects in strength group performed two circuits of resistance exercise (6 exercises with 10 repetition of 65–70% of one repetition maximum), while endurance group performed 30 min running with 65–70% of maximal heart rate. Blood was obtained pre and post-exercise to determine changes in serum BDNF, IGF-1 and platelets. Results After exercise, both the strength and endurance groups showed significant increases in serum BDNF and IGF-1 concentrations and platelets at post-exercise and in comparison to control group (p < 0.05). In addition, no statistically significant differences were detected between the strength and endurance groups at post-exercise. Conclusion Our findings indicate that both the strength and endurance interventions are effective in elevating BDNF, IGF-1, and platelets, without significant differences between them.


Author(s):  
Ella Nissan ◽  
Abdulla Watad ◽  
Arnon D. Cohen ◽  
Kassem Sharif ◽  
Johnatan Nissan ◽  
...  

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case–control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student’s t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan–Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.


Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 197
Author(s):  
Hiroaki Okawa ◽  
Missaka M.P. Wijayagunawardane ◽  
Peter L.A.M. Vos ◽  
Osamu Yamato ◽  
Masayasu Taniguchi ◽  
...  

This study investigated the efficacy of intrauterine infusion of a chitosan solution (CHT) on uterine recovery in early postpartum dairy cows with or without endometritis, and their subsequent reproductive performance. In Experiment 1, cows with endometritis at 3 weeks postpartum were administered CHT (n = 5) and prostaglandin F2α (PGF2α) (n = 4). Untreated cows (n = 7) served as the control group. In Experiment 2, 18 cows with a normally recovered uterus at the fresh cow check (mean, 35 days postpartum) were assigned to the CHT (n = 10) and control (n = 8) groups, and intrauterine infusion was conducted in the CHT group. Overall, in Experiment 1, the percentage of polymorphonuclear leukocytes significantly declined in the CHT group (32.3 ± 10.2 to 5.5 ± 2.4, p < 0.05) from week 3 to week 5, but no decline occurred in the PGF2α and control groups. In Experiment 2, the CHT and control groups showed no significant differences in reproductive parameters, suggesting the absence of adverse effects of CHT on fertility. These results suggest that intrauterine infusion of CHT in the early postpartum period effectively accelerates uterine recovery from endometritis and might be a suitable replacement for PGF2α administration.


2021 ◽  
Vol 22 (3) ◽  
pp. 1239
Author(s):  
Matilde Zaballos ◽  
Mercedes Power ◽  
María Iluminada Canal-Alonso ◽  
María Ángeles González-Nicolás ◽  
Wenceslao Vasquez-Jimenez ◽  
...  

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.


Author(s):  
Aaron R. Caldwell ◽  
Megan E. Rosa-Caldwell ◽  
Carson Keeter ◽  
Evan C. Johnson ◽  
François Péronnet ◽  
...  

<b><i>Background:</i></b> Debate continues over whether or not individuals with low total water intake (TWI) are in a chronic fluid deficit (i.e., low total body water) [<xref ref-type="bibr" rid="ref1">1</xref>]. When women with habitually low TWI (1.6 ± 0.5 L/day) increased their fluid intake (3.5 ± 0.1 L/day) for 4 days 24-h urine osmolality decreased, but there was no change in body weight, a proxy for total body water (TBW) [<xref ref-type="bibr" rid="ref2">2</xref>]. In a small (<i>n</i> = 5) study of adult men, there were no observable changes in TBW, as measured by bioelectrical impedance, after increasing TWI for 4 weeks [<xref ref-type="bibr" rid="ref3">3</xref>]. However, body weight increased and salivary osmolality decreased indicating that the study may have been underpowered to detect changes in TBW. Further, no studies to date have measured changes in blood volume (BV) when TWI is increased. <b><i>Objectives:</i></b> Therefore, the purpose of this study was to identify individuals with habitually low fluid intake and determine if increasing TWI, for 14 days, resulted in changes in TBW or BV. <b><i>Methods:</i></b> In order to identify individuals with low TWI, 889 healthy adults were screened. Participants with a self-reported TWI less than 1.8 L/day (men) or 1.2 L/day (women), and a 24-h urine osmolality greater than 800 mOsm were included in the intervention phase of the study. For the intervention phase, 15 participants were assigned to the experimental group and 8 participants were assigned to the control group. The intervention period lasted for 14 days and consisted of 2 visits to our laboratory: one before the intervention (baseline) and 14 days into the intervention (14-day follow-up). At these visits, BV was measured using a CO-rebreathe procedure and deuterium oxide (D<sub>2</sub>O) was administered to measure TBW. Urine samples were collected immediately prior, and 3–8 h after the D<sub>2</sub>O dose to allow for equilibration. Prior to each visit, participants collected 24-h urine to measure 24-h hydration status. After the baseline visit, the experimental group increased their TWI to 3.7 L for males and 2.7 L for females in order to meet the current Institute of Medicine recommendations for TWI. <b><i>Results:</i></b> Twenty-four-hour urine osmolality decreased (−438.7 ± 362.1 mOsm; <i>p</i> &#x3c; 0.001) and urine volume increased (1,526 ± 869 mL; <i>p</i> &#x3c; 0.001) in the experimental group from baseline, while there were no differences in osmolality (−74.7 ± 572 mOsm; <i>p</i> = 0.45), or urine volume (−32 ± 1,376 mL; <i>p</i> = 0.89) in the control group. However, there were no changes in BV (Fig. <xref ref-type="fig" rid="f01">1</xref>a) or changes in TBW (Fig. <xref ref-type="fig" rid="f01">1</xref>b) in either group. <b><i>Conclusions:</i></b> Increasing fluid intake in individuals with habitually low TWI increases 24-h urine volume and decreases urine osmolality but does not result in changes in TBW or BV. These findings are in agreement with previous work indicating that TWI interventions lasting 3 days [<xref ref-type="bibr" rid="ref2">2</xref>] to 4 weeks [<xref ref-type="bibr" rid="ref3">3</xref>] do not result in changes in TBW. Current evidence would suggest that the benefits of increasing TWI are not related changes in TBW.


2013 ◽  
Vol 304 (6) ◽  
pp. R415-R422 ◽  
Author(s):  
Cengiz Z. Altuntas ◽  
Firouz Daneshgari ◽  
Elias Veizi ◽  
Kenan Izgi ◽  
Fuat Bicer ◽  
...  

The pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is poorly understood. Inflammatory and autoimmune mechanisms may play a role. We developed a murine model of experimental autoimmune prostatitis (EAP) that mimics the human phenotype of CP/CPPS. Eight-week-old mice were immunized subcutaneously with prostate-specific peptides in an emulsion of complete Freund's adjuvant. Mice were euthanized 10 days after immunization, and lymph node cells were isolated and assessed for recall proliferation to each peptide. P25 99–118 was the most immunogenic peptide. T-cell and B-cell immunity and serum levels of C-reactive protein and nitrate/nitrite levels were evaluated over a 9-wk period. Morphometric studies of prostate, 24-h micturition frequencies, and urine volume per void were evaluated. Tactile referred hyperalgesia was measured using von Frey filaments to the pelvic region. The unpaired Student's t-test was used to analyze differences between EAP and control groups. Prostates from p25 99–118-immunized mice demonstrated elevated gene expression levels of TNF-α, IL-17A, IFN-γ, and IL-1β, not observed in control mice. Compared with controls, p25 99–118-immunized mice had significantly higher micturition frequency and decreased urine output per void, and they demonstrated elevated pelvic pain response. p25 99–118 immunization of male SWXJ mice induced prostate-specific autoimmunity characterized by prostate-confined inflammation, increased micturition frequency, and pelvic pain. This autoimmune prostatitis model provides a useful tool for exploring the pathophysiology and new treatments.


2021 ◽  
pp. 1-6
Author(s):  
Yi Zheng ◽  
Fuding Bai ◽  
Nan Zhang ◽  
Huifeng Wu

<b><i>Introduction:</i></b> The aim of this study was to investigate the association of transrectal ultrasound (TRUS)-guided prostate biopsy with voiding impairment and the efficacy of doxazosin treatment. <b><i>Methods:</i></b> A prospective observational study including 200 male patients undergoing TRUS-guided prostate biopsy was performed between May 2020 and December 2020. One hundred patients underwent biopsy with doxazosin (doxazosin group). The remaining 100 patients underwent biopsy without doxazosin (control group). All patients were questioned regarding post-biopsy voiding difficulty and acute urinary retention. The International Prostate Symptom Score (IPSS), maximal urinary flow rate (Q<sub>max</sub>), and residual urine volume were recorded before biopsy and at 7 and 30 days after biopsy. <b><i>Results:</i></b> There were no significant differences in baseline parameters between the two groups. The rate of post-biopsy voiding difficulty in the doxazosin group was significantly lower than that in the control group. Compared with baseline values, doxazosin treatment significantly improved IPSS, quality of life scores, and Q<sub>max</sub> after biopsy (<i>p</i> &#x3c; 0.05). The baseline values of IPSS and prostate size may be risk factors for post-biopsy voiding difficulty. <b><i>Conclusion:</i></b> TRUS-guided prostate biopsy causes transient voiding impairments, which may be improved by doxazosin treatment.


INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (04) ◽  
pp. 34-38
Author(s):  
P Bommannavar ◽  
◽  
K. Patil

The present study was undertaken to establish the diuretic activity of alcoholic and aqueous extract of dried rhizomes of Curcuma amada Roxb in rats. Alcoholic and aqueous extracts of rhizomes were administered to experimental male Wistar rats orally at doses of 250 and 500 mg/kg and compared with furosemide (10 mg/kg) as the reference standard. The parameters measured for diuretic activity were total urine volume, urine electrolyte concentration such as sodium, potassium and chloride have been evaluated. The rats treated with alcoholic and aqueous extract of Curcuma amada in a dose of 250 and 500 mg/kg showed higher urine output when compared to the respective control. Both alcoholic and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group. The result indicates that alcoholic and aqueous extract is an effective natriuretic and kaliuretic diuretic, which supports the traditional claim about the Curcuma amada Roxb being used as diuretics.


2021 ◽  
Vol 34 (2) ◽  
pp. 198-204 ◽  
Author(s):  
Suherni Susilowati ◽  
Trilas Sardjito ◽  
Imam Mustofa ◽  
Oky Setio Widodo ◽  
Rochmah Kurnijasanti

Objective: The aim of this study was to ascertain the effects of adding green tea extract (GTE) to skim milk-egg yolk (SM-EY) extender on both the quality of post-thawed bull semen and the pregnancy rates of the recipient cows.Methods: Twelve ejaculates from four Simmental bulls, aged 3 to 5 years and weighing 900 to 950 kg, were diluted SM-EY extender, added with 0, 0.05, 0.1, and 0.15 mg GTE/100 mL extender and then frozen. After four weeks storage in liquid nitrogen, the sperm were thawed and evaluated for viability, motility, intact plasma membrane (IPM), and DNA fragmentation. Meanwhile, the estrus cycles of 48 recipient cows were synchronized by intramuscular administration of a single injection of 5 mg prostaglandin F2α. Estrus cows were divided into four equal groups and inseminated artificially 18 to 20 h after the onset of estrus by using semen from each extender group. Pregnancy was diagnosed by measuring serum progesterone levels at 21 days, followed by transrectal palpation 90 days after insemination.Results: The findings revealed that adding 0.1 mg of GTE/100 mL extender produced the highest percentages of sperm viability (70.67%±1.75%), motility (69.17%±1.47%), and IPM (69.23%±1.21%) and the lowest percentage of DNA fragmentation (3.00%±0.50%). The pregnancy diagnosis revealed that all cows (36/36) inseminated using frozen semen in GTE addition extender were pregnant (pregnancy rate 100%), whereas the pregnancy rate of the control group was 83.33% (10/12).Conclusion: It may be concluded that 0.1 mg GTE/100 mL extender yields the best quality of spermatozoa and that all variants doses of GTE in extender produce a higher pregnancy rate among recipient cows.


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