Urinary Elimination Research Articles

Radiation Safety Considerations of Household Waste Disposal After Release of Patients Who Have Received [177Lu]Lu-PSMA-617.

Patients with metastatic prostate cancer are more likely than other groups to present for radiopharmaceutical therapy with urinary incontinence due to complications from prior local prostate cancer treatment. A consequence of urinary incontinence in patients receiving radiopharmaceutical therapy is the potential production of contaminated solid waste, which must be managed by the licensee and, at home, managed by and disposed of by the patient. Prolonging the patient stay in the treating facility after radiopharmaceutical therapy administration, until the first urinary void or potentially overnight, may moderately reduce the quantity of contaminated waste being managed by the patient at home. However, this approach does not fully mitigate the need for a patient waste-management strategy. In this brief communication, the relative radiation safety merits of contaminated waste disposal in the normal household waste stream in comparison to other waste management strategies are evaluated.

Prevalence, affecting factors and relationship with toileting behaviors of lower urinary tract symptoms in pregnant women: a cross-sectional study.

This study aimed to determine factors associated with lower urinary tract symptoms and their prevalence in pregnant women, and to examine the relationship between these symptoms and toileting behavior. The study included 502 pregnant women who completed the Bristol Female Lower Urinary Tract Symptoms-Short Form and the Toileting Behavior-Women's Elimination Behaviors Scale. The prevalence of at least one symptom in terms of urinary storage, voiding, urinary incontinence, sexual function, and quality of life dimensions in pregnant women were 99%, 54.8%, 60.4%, 19.7%, and 72.5%, respectively. The results showed that the lower urinary tract symptoms of pregnant women were related to premature voiding (developing the habit of voiding when there is less than 260 ml of urine in the bladder), being in the third trimester of pregnancy, the presence of stress urinary incontinence during or after pregnancy and history of urinary tract infection. Furthermore, it was found that pregnant women's total Bristol Female Lower Urinary Tract Symptoms-Short Form score had a weak correlation with their Toileting Behavior-Women's Elimination Behaviors Scale general total score, and scores in the subsections on premature voiding, delayed voiding, and straining for voiding. Given that lower urinary tract symptoms are common among pregnant women, women should be offered antenatal training on lower urinary tract symptoms and preventative measures early on in their pregnancy to ensure they develop healthy toileting habits.

A Case of Large Cervical Leiomyoma

Uterine Leiomyoma or Myoma or commonly favorite named Fibroid is a most common entity of genital organ tumor. It isalmost benign tumor of smooth muscle origin where smooth muscle fiber and fibrous connective tissue intermingled togetheroften found in uterus. Although it is a disease of nulliparous but in perspective of our country it diagnosed in patient's havingone or two child because of early marrital status. Tumor varies in number 1-200 and also varies different clinical features andseverity depending site of presentation. Leiomyoma is generally slowly progressive disease but sometimes it grows veryrapidly. With the advent of Ultrasonography it is incidentally diagnosed often with asymptomatic cases. UsuallyUltrasonography is the single most predictor of investigation1 from very early cases although MRI is helpful. Asymptomatic large Fibroid present with various unusual symptoms like pressure symptom of surrounding structure or feelingof heaviness of lower abdomen or fullness of abdomen. Large cervical Fibroid is a uncommon presentation with mainly urinarydifficulties where patients chief complaints is frequent micturation and incomplete voiding of urine without significantmenstrual abnormalities. The described cases for urinary complain patient consulted with urologist and referred as a largecervical Fibroid diagnosed by sonography. This article illustrates a case of 34 years old lady present with frequent micturationand incomplete voiding of urine that developed last 5-6 months duration. Total abdominal hysterectomy performed,histologically the specimen showed benign uterine leiomyoma. Post operative circumstance uneventful evaluation occur andpatient back to home with normal duration hospital stay.

Comparative Effect between Antidepressants and D-phenylalanine, a Phenethylamine Precursor, in an Animal Model of Depression

A relevant role has been attributed to phenethylamine in depressive disorders. It has been measured in human urine and rat brain in pathological conditions and after drug administration. Furthermore, a clinical correlation has been proposed between urinary elimination and depressive symptoms. Furthermore, its metabolic predecessor, D-phenylalanine, has been used as an antidepressant drug in the treatment of depressive disorders. The use of this amino acid has been realized alone, or in combination with classical antidepressants. In the present study, we tried to characterize its behavioural profile comparing it with imipramine and fluoxetine. Antidepressant drugs have been studied using diverse animal models. We used here the Porsolt test, or Forced Swimming Test (FST), measuring times of climbing, swimming and resting. When a comparison was performed between groups in climbing behaviour, significant differences were observed between imipramine treated group and saline controls (p < 0.05), and imipramine versus fluoxetine and D-phenylalanine (p < 0.01). When swimming was evaluated, clear differences between D-phenylalanine and the other groups were observed (p < 0.001). Additionally, a significant difference was also observed between imipramine and fluoxetine (p < 0.01). When resting was evaluated, high differences between D-phenylalanine versus all other groups were shown (p < 0.001). Observed behavioural profile was according to serotonergic antidepressant drugs effects. It is supported by the fact that swimming behaviours were increased, and a correlative decrease in resting was also present. We conclude that D-phenylalanine showed higher antidepressant potency than other classical antidepressants, at least at the doses used.

#5565 USEFULNESS OF URINARY BIOCHEMISTRY IN THE FOLLOW-UP OF PATIENTS WITH CHRONIC KIDNEY DISEASE STAGES 3B-5NOD

Abstract Background and Aims Ion and protein determinations in a simple urine sample are simple and inexpensive laboratory tests that reflect well ion balance and proteinuria. However, they are underused. Evidence of their usefulness in estimating 24-hour urine biochemistry in patients with chronic kidney disease (CKD) would allow widespread use of these tests and would help to optimize therapies. It would also avoid 24-hour urine collections. To evaluate In CKD stages G3b-5noD the accuracy of equations that estimate, through simple urine sampling, creatinine, protein, and ions in 24-hour urines. Method Retrospective observational study in incident adult patients with CKD G3b-5noD from the nephrology outpatient clinic in a Madrid university hospital, with a follow-up of at least two years and with at least one simultaneous determination of biochemistry in a simple urine sample and in 24-hour urine. The 24-hour urine analyses were restricted to those that were estimated to be well collected because urinary creatinine was between 15–25 mg/kg in men and 10–20 mg/kg in women. Correlation, bias (mean differences between estimated and measured analyte), accuracy (percentage of samples estimated at 15–30 or 50% of the measured value - P15, P30, P50) and agreement by the Bland-Altman method were analyzed. CKD progression was defined by the mean annual and percentage decrease in eGFR and the renal event at follow-up as loss of more than 40% of eGFR or entry into renal replacement therapy or conservative-palliative renal treatment. Kawasaki, Tanaka and CKD-epi (Table 1) equations were used. Results The analyzed cohort was made up of 300 patients with a median follow-up of 72 (25) months. Mean eGFR was 32.8 (9.2) ml/min/1.73m2 and mean protein/creatinine ratio was 1,180 (1,740) mg/g. During follow-up 30.7% started renal replacement therapy or conservative and palliative treatment. Twenty-one patients (7%) died. The estimation of 24-hour urine creatinine by CKD-EPI equation showed excellent correlation and accuracy with measured urinary creatinine (r = 0.887; P30: 96.1% in 464 urines). Accuracy was maintained regardless of age and CKD stage. Formulas that, using single urine samples, estimate 24-hour urine elimination of Na and K correlated well with 24-hour urine measurements, but with high dispersion, especially with Na. For Na, the Tanaka and CKD-EPI formulas had the highest performance (r = 0.540; 0.532; P30: 52.6; 54.5%; bias: -14.4; -16.1 mmol, Tanaka and CKD-EPI respectively for 464 urines). These values make them useful for population studies but not for individualized analysis. For K, the Kawasaki and CKD-EPI formulas were the most suitable (r = 0.712; 0.612; P30 = 74.6; 72.4%; bias: 4.2; 5.5 mmol; Kawasaki and CKD-EPI respectively for 464 urines). These results make them useful for both population-based studies and individualized analyses. Patients with Nao < 87 mmol/day (salt-poor diet) estimated by CKD-EPI, Kawasaki or Tanaka and/or Na/K ratio < 2 directly measured had less eGFR loss at follow-up and fewer renal events. Urinary K elimination measured or estimated did not influence renal prognosis. Proteinuria measured in 24-hour urine correlated much better with proteinuria estimated by CKD-EPI in a single urine sample than with the protein/creatinine ratio (r: 0.900 vs. 0.801; mean bias: 92.2 vs. 486 mg; P30: 72.0 vs. 42.7%; CKD-EPI vs. Proto/Cro in 464 24-hour urine samples). Conclusion Urinary biochemistry in a single urine sample in patients with advanced CKD (stages G3b-5noD) is a useful tool for estimating 24-hour urine biochemistry and to identify scenarios of increased progression of renal disease.

Quantifying whole bladder biomechanics using the novel pentaplanar reflected image macroscopy system.

Optimal bladder compliance is essential to urinary bladder storage and voiding functions. Calculated as the change in filling volume per change in pressure, bladder compliance is used clinically to characterize changes in bladder wall biomechanical properties that associate with lower urinary tract dysfunction. But because this method calculates compliance without regard to wall structure or wall volume, it gives little insight into the mechanical properties of the bladder wall during filling. Thus, we developed Pentaplanar Reflected Image Macroscopy (PRIM): a novel ex vivo imaging method to accurately calculate bladder wall stress and stretch in real time during bladder filling. The PRIM system simultaneously records intravesical pressure, infused volume, and an image of the bladder in five distinct visual planes. Wall thickness and volume were then measured and used to calculate stress and stretch during filling. As predicted, wall stress was nonlinear; only when intravesical pressure exceeded ~ 15mmHg did bladder wall stress rapidly increase with respect to stretch. This method of calculating compliance as stress vs stretch also showed that the mechanical properties of the bladder wall remain similar in bladders of varying capacity. This study demonstrates how wall tension, stress and stretch can be measured, quantified, and used to accurately define bladder wall biomechanics in terms of actual material properties and not pressure/volume changes. This method is especially useful for determining how changes in bladder biomechanics are altered in pathologies where profound bladder wall remodeling occurs, such as diabetes and spinal cord injury.

Urinary Excretion of Ecdysterone and Its Metabolites Following Spinach Consumption.

The phytosteroid ecdysterone is present in spinach. In this study, the urinary elimination of ecdysterone and its metabolites in humans is investigated following spinach consumption of two different culinary preparations. Eight participants (four males, four females) ingested 950(27.1)g sautéed spinach (average [±standard deviation (SD)]) and 912(70.6)g spinach smoothie as second intervention after washout. Post-administration urines are analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). After intake of both preparations, ecdysterone and two metabolites, 14-deoxy-ecdysterone, and 14-deoxy-poststerone, are excreted in urine. The maximum concentration of ecdysterone is ranging from 0.09 to 0.41µgmL-1 after sautéed spinach and 0.08-0.74µgmL-1 after smoothie ingestion. The total excreted amount(mean%[±SD]) in the urine as a parent drug plus the metabolites is only 1.4(1.0) for both sautéed spinach and smoothie. The apparent sex related differences in 14-deoxy-poststerone excretion will need further investigations. Only a small proportion of ecdysterone from spinach is excreted into urine. No significant differences are found in concentration and recovered amount(%) of ecdysterone, 14-deoxy-ecdysterone, and 14-deoxy-poststerone in urine between sautéed spinach and smoothie ingestion. A discrimination between ecdysterone from food or preparations will be challenging based on urinary concentrations only, at least for later post-administration samples.

A comparative review on In-vivo and In-vitro screening models for diuretic agents

Diuretics are medications that aid in the elimination of excess urine. Water, electrolytes, and metabolic waste are all found in urine. The anatomy and physiology of the renal excretion system are the topics of the current study. Along with the reasonable diuretic activity it also highlights the kidney's involvement in renal excretion. The mechanism of several diuretic classes is connected to their active target site in this overview. Diuretics have previously demonstrated their clinical efficacy in treating conditions including hypertension, renal failure, nephritic syndrome, and others. Here, several in-vitro and screening models demonstrate their clinical relevance. The logical goal, experimental methods, and assessment criteria of diverse screening models of diuretic action are highlighted in the current study. It also highlights the value and significance of these screening methods for determining the efficacy and safety of various members of various types of diuretic medicines. This review also revealed how some screening model improvements were successful. Studying the diuretic potential of various drugs is therefore absolutely helpful. In the end, the current review establishes a robust framework for dosage modification and fatal impact research of diverse kinds of diuretics. Thus, this study provides some suggestions for choosing cutting-edge methods to check the activity of diuretics. It also exposes the effects of the creation and adjustment of these screening methods, making them more effective in the future for assessing the diuretic potential of various diuretics agents.

Role of circadian rhythms and melatonin in bladder function in heath and diseases

The circadian system modulates all visceral organ physiological processes including urine storage and voiding. The "master clock" of the circadian system lies within suprachiasmatic nucleus of the hypothalamus while "peripheral clocks" are found in most peripheral tissue and organs, including the urinary bladder. Disruptions of circadian rhythms can cause organ malfunction and disorder or exacerbate pre-existing ones. It has been suggested that nocturia, which develops mostly in the elderly, could be a circadian-related disorder of the bladder. In the bladder, many types of gap junctions and ion channels in the detrusor, urothelium and sensory nerves are likely under strict local peripheral circadian control. The pineal hormone, melatonin, is a circadian rhythm synchroniser capable of controlling a variety of physiological processes in the body. Melatonin predominantly acts via the melatonin 1 and melatonin 2 G-protein coupled receptors expressed in the central nervous system, and many peripheral organs and tissues. Melatonin could be beneficial in the treatment of nocturia and other common bladder disorders. The ameliorating action of melatonin on bladder function is likely due to multiple mechanisms which include central effects on voiding and peripheral effects on the detrusor and bladder afferents. More studies are warranted to determine the precise mechanisms of circadian rhythm coordination of the bladder function and melatonin influences on the bladder in health and diseases.

Lower Urinary Tract Symptoms in Female Nurses: Evidence from the Nurse Urinary Related Health Study of China

Aims. To estimate the prevalence and bother of lower urinary tract symptoms (LUTS) and the work-related and individual factors associated with LUTS among a representative sample of female nurses. Background. A healthy nursing workforce is essential to advance global health goals, especially during times of extraordinary demand for nursing care. LUTS frequently occur and persist in women and are correlated with multiple negative health outcomes and diminished work engagement and productivity. However, the study of LUTS among female nurses failed to receive sufficient attention from researchers. Methods. We used baseline data for 13,191 female nurses in China collected for the prospective cohort study, the Nurse Urinary Related Health Study (NURS). We assessed nurses’ self-reported LUTS and symptom-related bother using the International Consultation on Incontinence Questionnaire-Female LUTS. We used descriptive statistics to summarize LUTS prevalence and its related bother and a mixed-effects logistic regression model to test the effects of work-related and individual factors on LUTS. Results. Most of the participants in this study were younger than 40 years old (82.9%), were married (74.8%), and had given birth once or never (73.7%). Few participants had chronic diseases (3.4%), consumed alcohol (7.3%), smoked (0.4%), or had overweight/obesity (27.7%). The prevalence of any LUTS was 51.1%, and over 50% of the nurses with LUTS in this study had experienced moderate or severe bother, except for urinary frequency. Working longer than five years, more than 40 hours per week, and in Level A, major tertiary hospitals were found to be risk factors of LUTS, and a nurse-to-bed ratio higher than 0.40 was found to be a protective factor. Increased fluid intake also was found to be a protective factor of LUTS in nurses, and having chronic constipation was found to be a risk factor. Conclusions. LUTS are highly prevalent and severely bothersome among female nurses in China, despite the fact that the female nurses in this study were relatively young, healthy, had few childbirths, and were living healthy lifestyles. This finding warrants remedial action that is related to both behavioral and environmental factors to ensure a healthy nursing workforce. Nurses cannot reasonably be expected to contribute to global health when one of their basic needs as humans, i.e., the normal function of urinary elimination, is ignored. Implications for Nursing Management. Nurse managers should be aware that nurses’ basic needs regarding urination are negatively affected by LUTS and related bother. Nurse managers should address LUTS-related problems on multiple levels, including overseeing and reporting LUTS in nurses, exploring innovative care models to mitigate the negative effects of excessive workloads on nurses, and remodeling the nursing culture and encouraging positive coping behaviors for the self-health of nurses.

Women's expectations of health care providers in the labor and delivery room in the Kurdistan Region of Iraq

Background and objective: The World Health Organization recognizes the importance of positive childbirth experience. In Iraq, patient satisfaction during maternity care visits is not routinely collected. This study was aimed to find out the women’s expectation during labor from physicians and midwives and associated factors such as socio-demographic and obstetrical characteristics. Methods: This cross-sectional study was conducted in Erbil city, located in the Kurdistan region of Iraq. A total of 1,500 women were targeted while they were accompanying another person, including children, to receive health services in Erbil and eventually 1,196 participated in the study. Data were collected through direct interviews after receiving informed oral consent. Participants were asked to describe their expectations for childbirth using an open-ended question. Responses were then grouped and categorized into 20 expectation items based on overlapping themes. Chi-square tests were used to identify associations with key socio-demographic and obstetric characteristics. Results: Level of expectation was significantly associated with education (illiterate and high education, P = 0.028),residency (suburban, P = 0.003), parity (grand multipara, P = 0.001), satisfaction with care (those satisfied, P <0.001), and satisfaction with provider communication (those satisfied, P <0.001). This study found that positive and calming verbal and non-verbal expressions, environmental control, encouragement of different positions and mobilization, hygiene, promotion of urinary elimination, and instruction on breathing and relaxation are highly expected by parturient women. Conclusion: Understanding women’s expectations in the delivery room is critical to health care providers in order to make appropriate care plan and support women to have a positive birth experience and to meet expectations.

Development and validation of LC–MS/MS methods for the determination of EVT201 and its five metabolites in human urine: Application to a mass balance study

In this study, two simple and accurate LC–MS/MS methods were firstly developed and validated to quantify EVT201, a new partial GABAA receptor agonist used for the treatment of insomnia, and its metabolites comprising M1, M2, M3, M4 and M6 in human urine. The analytes in urine samples were determined after simple dilution, and ideal chromatographic separations were obtained on C18 columns using gradient elution. The assays were performed in MRM mode on AB QTRAP 5500 tandem mass spectrometry (ESI+). The concentration ranges (ng/mL) of analytes in human urine were as follows: EVT201, 1.00 to 36.0; M1, 1.40 to 308; M2, 2.00 to 72.0; M3, 5.00 to 1100; M4, 2.00 to 300; and M6, 2.80 to 420. The methods were fully validated including selectivity, carryover, matrix effect, recovery, linearity, accuracy, precision, dilution integrity and stability, and acceptable criteria were obtained. The methods were successfully applied to a mass balance study of EVT201. The results showed that the total cumulative urinary excretion rate of EVT201 and its five metabolites was 74.25 ± 6.50%, which suggested that EVT201 had high oral bioavailability, and urinary elimination was its major excretion pathway in human.

Norfloxacin degradation in synthetic human urine using nickel converter slag-laterite heterogeneous Electro-Fenton process

Human urine is a point source of environmental antibiotic-related microcontaminants. Thus, developing dedicated treatment technologies for the effective degradation of urine antibiotics is highly desirable in large-scale human urine reuse. This work studied the antibiotic removal in synthetic human urine by the nickel converter slag-laterite (NCS-LA) heterogeneous Electro-Fenton (heterogeneous-EF) process. The objective was to assess the feasibility of this advanced oxidation process (AOP) for antibiotic elimination in synthetic human urine. Results indicated that the artificial aeration mode of 0.5 L/min could reach 95.25 % norfloxacin (NOR) degradation efficiency in synthetic human urine under established conditions (catalyst dosage 60 g/L, initial pH 3, applied current 80 mA). The natural aeration mode (the NOR degradation efficiency was only 9.49 %) was unsuitable for a single chamber undivided reactor with graphite felt (GF) cathode and Ti/RuO2-IrO2 anode. In cycling experiments conducted in synthetic urine, NCS-LA showed excellent reusability and stability. The NOR degradation efficiency decreased by only 5.01 % after six cycles. The leaching concentrations of heavy metals (Fe, Ni, Co and Cu) after each cycle were low (0.01–3.72 mg/L). This strategy is expected to clear the way for the recovery and reuse of urine.

188Re-SSS Lipiodol Radioembolization in HCC Patients: Results of a Phase 1 Trial (Lip-Re-01 Study)

Despite the wide development of 90Y-loaded microspheres, 188Re-labeled lipiodol is still being used for radioembolization of hepatocellular carcinoma (HCC). However, the use of this latter compound is limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to 188Re-SSS lipiodol, a new and more stable compound. Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety based on Common Terminology Criteria for Adverse Events (AEs) of Grade ≥3 within 2 months. Secondary endpoints included bio-distribution assessed by scintigraphy quantification from 1 to 72 h, tumor to non-tumor uptake ratio (T/NT), as well as blood, urine and feces collection over 72 h, dosimetry, and response evaluation (mRECIST). Overall, 14 heavily pre-treated HCC patients were treated using a whole liver approach. The mean injected activity was 1.5 ± 0.4 GBq for activity Level 1 (n = 6), 3.6 ± 0.3 GBq for Level 2 (n = 6), and 5.0 ± 0.4 GBq for Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity (one liver failure; one lung disease). The study was prematurely discontinued unrelated to clinical outcomes. Uptake occurred in the tumor, liver, and lungs, and only sometimes in the bladder. The T/NT ratio was high with a mean of 24.9 ± 23.4. Cumulative urinary elimination and fecal eliminations at 72 h were very low, 4.8 ± 3.2% and 0.7 ± 0.8%, respectively. Partial response occurred in 21% of patients (0% in the first activity level; 37.5% in the others). The high in vivo stability of 188Re-SSS lipiodol was confirmed, resulting in encouraging responses for a Phase 1 study. As the 3.6 GBq activity proved to be safe, it will be used in a future Phase 2 study.

Asuhan Keperawatan Gangguan Eliminasi Urin pada Ny. K dengan Infeksi Saluran Kemih di Ruang Ar-Rahman RSI Purwokerto

Introduction: Urinary tract infection (UTI) or Urinarius Tractus Infection is a condition where there is a bacterial infection of microorganisms that occurs in the urinary tract. The occurrence of UTI is due to the presence of pathogenic microorganisms in the urinary tract. These microorganisms enter through direct contact from the nearest source of infection, hematogenous or lymphomatous. Symptoms of UTI are the desire to urinate that continues to be felt, pain or sensation of heat when urinating (this set of conditions is called anyang-anyang), turbid and sharp-smelling urine, frequent urination, bloody or purulent urine, in women generally the patient will feel pelvic pain, especially in the pelvic center and the bone area around the genitals Objectives: To describe nursing care in urinary tract infection patients who have impaired urinary elimination. Method: This research uses qualitative descriptive methods in the form of case studies. Nursing care was given to Mrs. K for 3 days. Data collection techniques obtained from the results of interviews, observations, and physical examinations Result: The problem of urinary elimination disorders that occur in patients with urinary tract infections can be overcome by conducting deep breath relaxation therapy to reduce the pain experienced by the patient, training the patient not to hold urination, and advising the patient to increase the frequency of drinking. The results obtained after the nursing action is the patient's pain gradually decreases, the frequency of urination is smooth even though it still feels pain when urinating Conclusion: After nursing treatment for 3x24 hours, the problem of urinary elimination disorders gradually improved characterized by an improved elimination pattern of decreased patient pain complaints.

Diuretic Effect of the Aqueous Extract of Cymbopogon nardus (L.) Rendle Compared with Furosemide in Wistar Rats

Cymbopogon nardus (L.) Rendle is one of the medicinal plants widely used in folk medicine to cure certain diseases. The current work aims to assess the diuretic potential of C. nardus using animal models. Urine electrolytes (sodium and potassium), serum electrolytes (sodium, potassium, and chloride), blood urea, creatinine, creatinine clearance, osmolar clearance, urinary osmolarity, and urine flow were determined. To assess the diuretic effect of the studied plant, four groups of rats were used (n = 6). The control group received 10 mL of water, the second and third groups received two doses of the plant (100 and 150 mg/kg bw), and the last group received furosemide (10 mg/kg bw), the experiment sustained for seven days. Urine flow and electrolytes levels were studied. The single dose of C. nardus extract significantly increased urine flow after oral administration. In addition, daily administration of both doses of C. nardus significantly elevated urine excretion, opposite to the first group. C. nardus enhanced the urine elimination of sodium and potassium. Importantly, both doses have no effect on serum potassium level. Creatinine clearance was significantly elevated in a dose-dependent manner. This information will be considered as a keystone for further studies forward in applying new process to isolate active compounds of C. nardus responsible for its biological properties.

Abstract 5546: Urine metabolomic biomarkers discovery for bladder cancer diagnostics

Abstract Current estimates in the United States for 2022 are about 81,180 new cases of bladder cancer diagnosis with about 17,100 deaths from the disease (American Cancer Society). Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the most common type of bladder cancer, approximately 70% of newly diagnosed TCC patients have non-muscle invasive bladder cancer (NMIBC) tumors. The gold standards for initial diagnosis and recurrence of TCC, cystoscopy and cytology, are both limited by their inability to visualize certain areas within the bladder or detect low grade tumors. Moreover, these tests are associated with false positive profiles, with potential for abnormal readouts even in individuals with no obvious signs of cancer. High recurrence rate predicates the need for constant monitoring of signs and symptoms associated with bladder disease following initial diagnosis, and non-invasive diagnostic modalities to detect both recurrent and primary early-stage tumors are a critical unmet need. In this study, comprehensive metabolomic profiling from human urine samples was used to identify and validate a panel of metabolites as potential biomarkers of bladder cancer. Urine samples from 439 total subjects (comprised of 66 bladder cancer, 119 history of bladder cancer but no bladder cancer at time of urine sampling, 58 hematuria subjects, 48 renal cell carcinoma, 58 prostate cancer, and 89 healthy subjects) were analyzed using a proprietary global untargeted metabolomic platform. A follow-up study to determine the reproducibility of the initial data set was conducted with 162 urine samples from subjects with bladder cancer that were either recurrent or primary, or with a negative diagnosis for bladder cancer with a previous history of bladder cancer or had hematuria or urinary voiding issues. Utilizing both data sets, eight biochemicals (lactate, gluconate, palmitoyl sphingomyelin, acetylcarnitine, choline phosphate, succinate, and adenosine) were identified as potential urine biomarkers for bladder cancer. In addition, 3-hydroxybutyrate (BHBA), 2-hydroxybutyrate (AHB), and adipate were identified as potential urine biomarkers for urological cancers. In total, 37 biochemicals have now been identified with having the potential to serve as urine bladder cancer biomarkers, and the majority of the biochemicals identified as biomarkers were associated with biochemical pathways previously shown to be perturbed in bladder tumors. The performance characteristics of the identified biochemicals in the detection of bladder cancer will be reported. Citation Format: Andrew J. Schwab, Matthew W. Mitchell, Edward D. Karoly, Rangaprasad Sarangarajan. Urine metabolomic biomarkers discovery for bladder cancer diagnostics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5546.

A3907, a systemic ASBT inhibitor, improves cholestasis in mice by multiorgan activity and shows translational relevance to humans.

Cholestasis is characterized by intrahepatic accumulation of bile constituents, including bile acids (BAs), which promote liver damage. The apical sodium-dependent BA transporter (ASBT) plays an important role in BA reabsorption and signaling in ileum, bile ducts, and kidneys. Our aim was to investigate the pharmacokinetics and pharmacological activity of A3907, an oral and systemically available ASBT inhibitor in experimental mouse models of cholestasis. In addition, the tolerability, pharmacokinetics, and pharmacodynamics of A3907 were examined in healthy humans. A3907 was a potent and selective ASBT inhibitor in vitro. In rodents, orally administered A3907 distributed to the ASBT-expressing organs, that is, ileum, liver, and kidneys, and dose dependently increased fecal BA excretion. A3907 improved biochemical, histological, and molecular markers of liver and bile duct injury in Mdr2-/- mice and also had direct protective effects on rat cholangiocytes exposed to cytotoxic BA concentrations in vitro . In bile duct ligated mice, A3907 increased urinary BA elimination, reduced serum BA levels, and prevented body weight loss, while improving markers of liver injury. A3907 was well tolerated and demonstrated target engagement in healthy volunteers. Plasma exposure of A3907 in humans was within the range of systemic concentrations that achieved therapeutic efficacy in mouse. The systemic ASBT inhibitor A3907 improved experimental cholestatic disease by targeting ASBT function at the intestinal, liver, and kidney levels, resulting in marked clearance of circulating BAs and liver protection. A3907 is well tolerated in humans, supporting further clinical development for the treatment of cholestatic liver diseases.

Endocannabinoids, anandamide and 2-AG, regulate mechanosensitivity of mucosal afferents in the Guinea pig bladder

Bladder afferents play a crucial role in urine storage and voiding, and conscious sensations from the bladder. Endocannabinoids, anandamide (AEA) and 2-arachidonolylglycerol (2-AG), are endogenous ligands of G-protein coupled cannabinoid receptors 1 and 2 (CB1 and CB2) found in the CNS and peripheral organs. They also have off-target effects on some ligand- and voltage-gated channels. The aim of this study is to determine the role of AEA and 2-AG in regulation of mechanosensitivity of probable nociceptive neurons innervating the bladder - capsaicin-sensitive mucosal afferents. The activity of these afferents was determined by ex vivo single unit extracellular recordings in the guinea pig bladder. A stable analogue of anandamide, methanandamide (mAEA) evoked initial excitatory response of mucosal afferents followed by potentiation of their responses to mechanical stimulation. In the presence of TRPV1 antagonist (AMG9810), mAEA's effect on mechanosensitivity switched from excitatory to inhibitory. The inhibitory effect of mAEA is due to activation of both CB1 and CB2 cannabinoid receptors since it was abolished by combined application of selective CB1 (NESS0327) and CB2 (SR144528) antagonists. 2-AG application evoked a brief excitation of mucosal afferents, without potentiation of their mechanosensitivity, followed by the inhibition of their responses to mechanical stimulation. CB2 receptor antagonist, SR144528 abolished the inhibitory effect of 2-AG. Our data indicated that anandamide and 2-AG have opposite effects on mechanosensitivity of mucosal capsaicin-sensitive afferents in the guinea pig bladder; mAEA potentiated while 2-AG inhibited responses of mucosal afferents to mechanical stimulation. These findings are important for understanding of the role of endocannabinoids in regulating bladder sensation and function.

Rats with Long-Term Cholestasis Have a Decreased Cytosolic but Maintained Mitochondrial Hepatic CoA Pool.

Previous studies showed that rats with long-term bile duct ligation have reduced coenzyme A stores per g of liver but maintained mitochondrial CoA stores. Based on these observations, we determined the CoA pool in the liver homogenate, liver mitochondria, and liver cytosol of rats with bile duct ligation for 4 weeks (BDL rats, n = 9) and sham-operated control rats (CON rats, n = 5). In addition, we tested the cytosolic and mitochondrial CoA pools by assessing the metabolism of sulfamethoxazole and benzoate in vivo and of palmitate in vitro. The hepatic total CoA content was lower in BDL than CON rats (mean ± SEM; 128 ± 5 vs. 210 ± 9 nmol/g), affecting all subfractions equally (free CoA (CoASH), short- and long-chain acyl-CoA). In BDL rats, the hepatic mitochondrial CoA pool was maintained, and the cytosolic pool was reduced (23.0 ± 0.9 vs. 84.6 ± 3.7 nmol/g liver; CoA subfractions were affected equally). The urinary excretion of hippurate after i.p. benzoate administration (measuring mitochondrial benzoate activation) was reduced in BDL rats (23.0 ± 0.9 vs. 48.6 ± 3.7% of dose/24 h), whereas the urinary elimination of N-acetylsulfamethoxazole after i.p. sulfamethoxazole administration (measuring the cytosolic acetyl-CoA pool) was maintained (36.6 ± 3.0 vs. 35.1 ± 2.5% of dose/24 h BDL vs. CON rats). Palmitate activation was impaired in the liver homogenate of BDL rats but the cytosolic CoASH concentration was not limiting. In conclusion, BDL rats have reduced hepatocellular cytosolic CoA stores, but this reduction does not limit sulfamethoxazole N-acetylation or palmitate activation. The hepatocellular mitochondrial CoA pool is maintained in BDL rats. Impaired hippurate formation in BDL rats is explained best by mitochondrial dysfunction.