Three-channel ion chromatograph for improved metabolic evaluation of urolithiasis

Abstract Background Urolithiasis is a multi-etiological disease resulting from a combination of environmental and genetic factors. One of the most challenging aspects of this disease is its high recurrence rate. For most patients, an in-depth metabolic evaluation may reveal the presence of urinary stones. The fact that different urinary stone-related compounds (USRCs) are measured by different methods renders the metabolic evaluation of urolithiasis quite tedious and complex. Methods A three-channel ion chromatograph (IC) that automatically measures the concentration of common metabolic indicators of urolithiasis in urine (i.e., oxalate, citrate, uric acid, calcium, and magnesium) was developed to improve the efficiency. To validate its precision and specificity, standard curves were prepared using working solution of these indicators. 100 standard solutions of these indicators were measured with our new IC and three other ICs as the control instruments; analyte concentrations in 100 24-h urine samples from volunteers and 135 calculi patients were also measured. Results All analytes had good linear relationships in concentration ranges of 0–10 mg/L. The precision experiments in the standard and urine samples showed that the measurement errors of the newly developed IC were all less than 5%. In urine, the recovery rate ranged from 99.6 to 100.4%, the coefficient of variation ranged from 1.39 to 2.99%, and the results matched between our newly developed IC and the control ICs. The results of the efficiency test showed that we can finish the analysis at the average number of 14 people per day with the new IC. While the average number in the control group is 3.85/day (p = 0.000). Conclusions Overall, this multi-channel system significantly improves the efficiency of metabolic evaluation while retaining accuracy and precision.

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Urine CA-2 as a biomarker for diagnosis urinary stone and prediction of its complications

10.21203/rs.3.rs-59394/v1 ◽

2020 ◽

Author(s):

Yuan-jing Leng ◽

Hai-bin Zhou ◽

Jiang-ling Fu ◽

Wen-juan Wang

Keyword(s):

Healthy Subjects ◽

Characteristic Curve ◽

Urinary Stone ◽

Urinary Stones ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Control ◽

The Mean ◽

The Difference ◽

The Relationship

Abstract PURPOSECarbonic anhydrase-2 (CA-2) plays a role in mineralization and calcification in organism. Strong evidence suggests that CA-2 is associated with urolithiasis. However, the relationship between CA-2 and urinary stone remains unclear. The study aimed to assess the association of urine CA-2 (uCA-2) level and the potential risk of urinary stone.METHODSFrom March 2017 to November 2019, a prospective cohort study was conducted on patients with urinary stones and healthy subjects to determine the pretreatment uCA-2 level detection by Enzyme linked immunosorbent assay (ELISA). The difference of uCA-2 level between patients with urinary stones and healthy subjects was compared. Then comparison between stone patients with complications and without complications was carried out as well as correlation analysis to detect factors associated with biomarker expression.RESULTS118 patients with urinary stones were into urinary stones group and 42 healthy subjects were into healthy control group. The mean pretreatment uCA-2 level was significantly higher in patients with urinary stones group than healthy controls group (P=0.028). Furthermore, The uCA-2 level was positive correlation with urinary stones complications (R=0.379, P=0.000), especially pain complications (R=0.524, P=0.000) and hematuria complications (R=0.374, P=0.000). Receiver operating characteristic curve (ROC) analysis that a uCA-2 level threshold of 10.94 ng/mL had 83.67% sensitivity and 68.12% specificity for predicting urinary stones complications. CONCLUSIONSExcessive uCA-2 excretion is a major risk factor for urinary stone. Our findings suggested that uCA-2 may be used as an unappreciated biomarker for the diagnosis urinary stone in patients and to predict its complications.

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Chemical Analysis of Urinary Stones

Journal of Society of Surgeons of Nepal ◽

10.3126/jssn.v19i2.24543 ◽

2016 ◽

Vol 19 (2) ◽

pp. 10-12

Author(s):

Ghanshyam Sigdel ◽

Nirmal Lamichhane ◽

Sudeep Raj K.C. ◽

W.K. Belokar

Keyword(s):

Chemical Analysis ◽

Large Scale ◽

Renal Stones ◽

Urinary Stone ◽

Stone Disease ◽

Urinary Stones ◽

Chemical Compositions ◽

Metabolic Evaluation ◽

Female Ratio ◽

Stone Formers

Introduction: Urinary stone disease is a common urological problem. Chemical analysis of the urinary stones is a part of metabolic evaluation of first time or recurrent stone formers. The report of chemical analysis of stones may obviate the need for complete metabolic evaluation or can direct metabolic evaluation. In this study we aim to find out the chemical compositions of urinary stones in our population, so that the result might serve as a baseline for the related research in future. Methods: A prospective study was carried out in our institute with the qualitative chemical analysis of urinary stones. All patients operated for different urinary stones by various methods were included in the study. Statistical analysis was done by using Statistical Package for the Social Sciences Software (SPSS) Program for windows ® version 18. Results: A total of 55 patients were included in the study. Male to female ratio was 1.75. Mean age was 41.45 years. Ureteric and renal stones were most common accounting to 49 and 31 percentage respectively. All stones contained calcium. Calcium, phosphate, oxalate and uric acid were the major constituents of the stones representing 100, 94.5, 85.5 and 80 percentage of the stone specimen. Other constituents were amino acids, carbonate, magnesium and cystine. Conclusions: Urinary stones are of mixed chemical compositions. Further large scale prospective studies along with other parameters of metabolic work up are recommended to know more about the chemical compositions of urinary stones and its utility in clinical practice.

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Benefaction of Herbals in the Management of Urolithiasis

Current Traditional Medicine ◽

10.2174/2215083806999201125122055 ◽

2020 ◽

Vol 06 ◽

Author(s):

Ankit Yadav ◽

Rina Das ◽

Dinesh Kumar Mehta ◽

Yatin

Keyword(s):

Urinary Tract ◽

Urinary Tract Obstruction ◽

Stone Formation ◽

Herbal Medicines ◽

Urinary Stone ◽

Stone Disease ◽

Urinary Stones ◽

High Recurrence Rate ◽

Industrialized Countries ◽

Forced Return

: Kidney stone formation or Urolithiasis is a common problem over many centuries with no guarantee of effective treatment and, a high recurrence rate. Urolithiasis is precipitation of insoluble and less soluble salt such as Oxalate and Phosphate in the urinary tract causing obstruction in the urethra resulting in renal colic and, hematuria. Approximately, 10-12% of the population in industrialized countries are severely affected by Urinary stones. In, only a few geographical areas is stone disease rare, e.g., in the coastal areas of Japan and Germany. It was believed that, 11% of people in India are suffering from urinary stone problems, and approximately 50% of these cases may lead to severe renal damage. Ultimately it causes severe health issues in terms of urinary tract obstruction, severe pain, and infection that adversely affects the health of individuals. Diuretics and narcotic analgesic like drugs which are used to prevent and cure urolithiasis are not effective in all cases and are costly, give quite common recurrences, risk long term fertility and, other potential side effects are observed. So, humans are forced return to Nature for safe remedies using herbal treatment. A great number of Indian medicinal plants have been investigated in the treatment of urolithiasis, and they have been reported to be safe and effective. In the present review, an effort has been made to highlight such herbal medicines which are potentially effective in the management of urolithiasis.

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Use of non-contrast computed tomography determined urinary stone fragility in predicting the outcome of extracorporeal shockwave lithotripsy treatment: a single-center study

Journal of Fatima Jinnah Medical University ◽

10.37018/xivf1000 ◽

2020 ◽

Vol 14 (2) ◽

pp. 59-63

Author(s):

Athar Hameed ◽

Khazir Hayyat Gondal

Keyword(s):

Shock Waves ◽

Renal Stone ◽

Plain Film ◽

Renal Stones ◽

Renal Calculus ◽

Urinary Stone ◽

Stone Disease ◽

Urinary Stones ◽

Fisher Exact Test

Background: Renal stones represent a common urological pathology where standard treatment advised is ESWL in current practice. However, NCCT based determination of stone fragility may help to predict the outcome of ESWL treatment, hence optimizing its clinical use. Therefore, this study evaluated the role of NCCT determined urinary stone fragility in predicting the outcome of ESWL treatment in local clinical settings. Patients and methods: One hundred patients with single renal calculus of 0.6-2 cm in size were included. NCCT based determination of stone fragility in HU units was done for all patients. Patients were then subjected to ESWL, with a maximum of 3000 shock waves given per ESWL session. Plain film and/or ultrasonography was used to monitor ESWL treatment progress with a final NCCT evaluation at 12 weeks to determine the clearance of the calculi for each patient. Association of NCCT based stone fragility and outcome of ESWL was statistically analyzed using Fisher exact test. Results: The mean age of the patients was 37.7 ± 10.9 years with 54% being male. Decreasing stone fragility on NCCT (high = <500HU, moderate = 500-1000HU, and high = 1000HU) required more number and intensity of ESWL sessions (1-2 visits and 3000-6000 shock waves for high stone fragility group, 3-5 visits and 7000-18000 shock waves for the moderate group, and 6 visits and >18000 shock waves for low fragility group, respectively) necessary for clearance of urinary stones (p<0.001). In 98% of patients, the clearance of urinary stones was excellent. Conclusion: Renal stone patients with NCCT determined high and moderate stone fragility show an optimal response after ESWL treatment, whereas, for low fragility renal stones attenuative treatment like percutaneous nephrolithotomy and/or ureteroscopy should be considered instead of ESWL. This approach can enable patient stratification before ESWL therapy ensuring better clinical management of the renal stone disease.

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Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽

10.3390/molecules26082194 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2194

Author(s):

Kamil Łuczykowski ◽

Natalia Warmuzińska ◽

Sylwia Operacz ◽

Iga Stryjak ◽

Joanna Bogusiewicz ◽

...

Keyword(s):

Thin Film ◽

Bladder Cancer ◽

High Performance ◽

Biomarker Discovery ◽

Solid Phase ◽

Biological Fluids ◽

Reversed Phase ◽

Control Group ◽

Metabolic Evaluation ◽

Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

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Urinary stone composition analysis and clinical characterization of 1520 patients in central China

Scientific Reports ◽

10.1038/s41598-021-85723-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daling Zhang ◽

Songchao Li ◽

Zhengguo Zhang ◽

Ningyang Li ◽

Xiang Yuan ◽

...

Keyword(s):

Calcium Oxalate ◽

Urinary Stone ◽

Geographic Region ◽

Central China ◽

Urinary Stones ◽

Composition Analysis ◽

Stone Composition ◽

Calcium Oxalate Stones ◽

Significant Difference ◽

Lower Urinary

AbstractA total of 1520 patients with urinary stones from central China were collected and analysed by Fourier transform infrared spectroscopy between October 1, 2016 and December 31, 2019. For all patients, age, sex, comorbidities, stone location, laboratory examination and geographic region were collected. The most common stone component was calcium oxalate (77.5%), followed by calcium phosphate (8.7%), infection stone (7.6%), uric acid (UA) stone (5.3%)and cystine (0.9%). The males had more calcium oxalate stones (p < 0.001), while infection stone and cystine stones occurred more frequently in females (p < 0.001). The prevalence peak occurred at 41–60 years in both men and women. UA stones occurred frequently in patients with lower urinary pH (p < 0.001), while neutral urine or alkaline urine (p < 0.001) and urinary infection (p < 0.001) were more likely to be associated with infection stone stones. Patients with high levels of serum creatinine were more likely to develop UA stones (p < 0.001). The proportion of UA stones in diabetics was higher (p < 0.001), and the incidence of hypertension was higher in patients with UA stones (p < 0.001). Compared to the other types, more calcium oxalate stones were detected in the kidneys and ureters (p < 0.001), whereas struvite stones were more frequently observed in the lower urinary tract (p = 0.001). There was no significant difference in stone composition across the Qinling-Huaihe line in central China except UA stones, which were more frequently observed in patients south of the line (p < 0.001).

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Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity

International Journal of Molecular Sciences ◽

10.3390/ijms22137205 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7205

Author(s):

Matheus V. C. Grahl ◽

Augusto F. Uberti ◽

Valquiria Broll ◽

Paula Bacaicoa-Caruso ◽

Evelin F. Meirelles ◽

...

Keyword(s):

Proteus Mirabilis ◽

Stone Formation ◽

Cell Types ◽

Bioinformatic Analysis ◽

Urinary Stone ◽

Enzymatic Properties ◽

Hek293 Cells ◽

Urinary Stones ◽

Isolated Cells ◽

Tnf Α

Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures’ supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca2+ and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases.

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Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models

Cancer & Metabolism ◽

10.1186/s40170-021-00249-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Malinee Thanee ◽

Sureerat Padthaisong ◽

Manida Suksawat ◽

Hasaya Dokduang ◽

Jutarop Phetcharaburanin ◽

...

Keyword(s):

Redox Regulation ◽

Treated Group ◽

Control Group ◽

High Recurrence Rate ◽

Nucleic Acid Metabolism ◽

In Vivo Models ◽

Tryptophan Degradation ◽

Xenograft Mice

Abstract Background Sulfasalazine (SSZ) is widely known as an xCT inhibitor suppressing CD44v9-expressed cancer stem-like cells (CSCs) being related to redox regulation. Cholangiocarcinoma (CCA) has a high recurrence rate and no effective chemotherapy. A recent report revealed high levels of CD44v9-positive cells in CCA patients. Therefore, a combination of drugs could prove a suitable strategy for CCA treatment via individual metabolic profiling. Methods We examined the effect of xCT-targeted CD44v9-CSCs using sulfasalazine combined with cisplatin (CIS) or gemcitabine in CCA in vitro and in vivo models and did NMR-based metabolomics analysis of xenograft mice tumor tissues. Results Our findings suggest that combined SSZ and CIS leads to a higher inhibition of cell proliferation and induction of cell death than CIS alone in both in vitro and in vivo models. Xenograft mice showed that the CD44v9-CSC marker and CK-19-CCA proliferative marker were reduced in the combination treatment. Interestingly, different metabolic signatures and significant metabolites were observed in the drug-treated group compared with the control group that revealed the cancer suppression mechanisms. Conclusions SSZ could improve CCA therapy by sensitization to CIS through killing CD44v9-positive cells and modifying the metabolic pathways, in particular tryptophan degradation (i.e., kynurenine pathway, serotonin pathway) and nucleic acid metabolism.

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Nutrition and Kidney Stone Disease

Nutrients ◽

10.3390/nu13061917 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1917

Author(s):

Roswitha Siener

Keyword(s):

Kidney Stone ◽

Fluid Intake ◽

Stone Formation ◽

Urinary Stone ◽

Stone Disease ◽

Urinary Stones ◽

Dietary Therapy ◽

Effective Prevention ◽

Kidney Stone Disease ◽

Nutrition And Diet

The prevalence of kidney stone disease is increasing worldwide. The recurrence rate of urinary stones is estimated to be up to 50%. Nephrolithiasis is associated with increased risk of chronic and end stage kidney disease. Diet composition is considered to play a crucial role in urinary stone formation. There is strong evidence that an inadequate fluid intake is the major dietary risk factor for urolithiasis. While the benefit of high fluid intake has been confirmed, the effect of different beverages, such as tap water, mineral water, fruit juices, soft drinks, tea and coffee, are debated. Other nutritional factors, including dietary protein, carbohydrates, oxalate, calcium and sodium chloride can also modulate the urinary risk profile and contribute to the risk of kidney stone formation. The assessment of nutritional risk factors is an essential component in the specific dietary therapy of kidney stone patients. An appropriate dietary intervention can contribute to the effective prevention of recurrent stones and reduce the burden of invasive surgical procedures for the treatment of urinary stone disease. This narrative review has intended to provide a comprehensive and updated overview on the role of nutrition and diet in kidney stone disease.

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Mobile Messaging Assisted Treatment (MMAT) for Patients with Methamphetamine Use Disorder: A Preliminary Randomized Controlled Trial (Preprint)

10.2196/preprints.26996 ◽

2021 ◽

Author(s):

Chun-Hung Lee ◽

Guan-Hsiung Liaw ◽

Wu-Chuan Yang ◽

Yu-Hsin Liu

Keyword(s):

New Technologies ◽

Readiness To Change ◽

Controlled Trial ◽

Rapid Development ◽

Urine Samples ◽

Current Evidence ◽

Control Group ◽

Therapeutic Effects ◽

Polysubstance Use ◽

Positive Urine

BACKGROUND Methamphetamine (MA) use disorder can cause various physical and psychological harms. Despite current evidence demonstrating the therapeutic effects of psychosocial interventions, finding an approach to increase patient adherence to treatment remains a real-world challenge. The rapid development of new technologies, such as mobile health (mHealth) systems, suggests the potential to provide real-time personalized care at any time and from any location, minimize barriers to treatment, maximize use, and promote the dissemination of accessible therapeutic tools in at-risk populations. OBJECTIVE Objectives of our study investigated the feasibility and effectiveness of implementing mHealth technology in the treatment of MA use disorder. METHODS The inclusion criteria were (a) a diagnosis of MA abuse or dependence as defined by the DSM-IV-TR (b) age between 18 and 65 years, (c) no initial diagnosis of severe physical or mental illness, such as schizophrenia or bipolar I disorder, at baseline of the survey, and (d) willingness to participate in standard outpatient treatment for 1 year. Participants were randomly allocated to either a mobile messaging–assisted treatment (MMAT) group which delivered relapse prevention and recovery skills or a control group following simple randomization procedures (computerized random numbers) without blinding. All participants were followed for 6 months. Treatment retention and results of monthly urine tests were analysed as outcome measures. Feasibility and participant satisfaction were also assessed based on patients’ experiences with MMAT. RESULTS 50 participants were allocated to MMAT group and 49 to control. The average retention was 142.42 ± 60.54 days for the MMAT group and 118.12 ± 73.41 days for the control group, with no significant differences between the two treatment groups (df = 1, p = .099). Compared with the control group, the MMAT group had fewer MA-positive urine samples (19.5% vs 29.6%, F = 9.116, p = .003). Moreover, the proportion of MA-positive urine samples was positively correlated with the frequency of MA use (r = .323, p = .001), severity of MA use disorder (r = 0.364, p < .001), and polysubstance use (r = .212, p = .035) and negatively correlated with readiness to change (r = -.330, p = .001). At 6-month follow-up, 55 participants who completed the study reported high satisfaction with receiving MMAT. There was no significant adverse effects reported. CONCLUSIONS Participants in this study diagnosed as having MA use had high adherence to MMAT, generally positive treatment outcomes, and favorable acceptance, which indicates that this type of intervention is feasible for individuals with MA use disorder. Therefore, this study supports the efficacy and feasibility of using mobile phones for treating people who use MA. Future studies should investigate MMAT’s ability to (a) engage patients in the assessment of their own symptoms and daily functioning, (b) increase patients’ self-awareness and self-management of symptoms, (c) improve patients’ ability to identify triggers and track their own disease progression, and (d) increase patients’ willingness to seek care when necessary. CLINICALTRIAL Study Registry: ISRCTN16586487 (https://doi.org/10.1186/ISRCTN16586487)

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