Decrease In Urinary Levels Research Articles

Shionone Relieves Urinary Tract Infections by Removing Bacteria from Bladder Epithelial Cells

In clinical practice, urinary tract infections (UTIs) are second only to respiratory infections in terms of infectious diseases. In recent years, drug resistance of Escherichia coli (E. coli) has increased significantly. The therapeutic effects of Shionone on UTI were assessed by modelling UTI in SD rats and SV-HUC-1 cells with E. coli solution. After treatment of Shionone, the UTI rat model showed a decrease in wet weight/body weight of bladder, as well as a reduction in cellular inflammatory infiltration of bladder tissue and a decrease in urinary levels of IL-6, IL-1β, and TNF-α. In addition, the levels of proinflammatory factors were significantly reduced in a dose-dependent manner in UTI cell model treated with different doses of Shionone (5, 10, and 20 μg/kg). The results of immunofluorescence analysis in both in vivo and in vitro experiments revealed that Shionone reduced bacterial load and the number of E. coli colonies growing on the plates was greatly reduced. These results suggested that Shionone has a good therapeutic effect on UTI, achieved by reducing bacterial load in bladder epithelial cells. The data presented here provide a basis for further research into the treatment of UTI.

Ameliorative effect of desloratadine against cisplatin-induced renal and testicular toxicity in rats: Attention to TLR4/NLRP3 inflammasome signaling pathway

Cisplatin (CIS) is a potent anticancer drug that is used in the treatment of different types of cancer. Owing to its serious side effects, its clinical use is considerably limited. Aims: This study was mapped to investigate the potential effects of desloratadine (DES) against CIS-induced nephrotoxicity and testicular injury. Main methods: DES (5 and 10 mg/kg) was orally administered for 10 days, and CIS was injected once (10 mg/kg, i.p.) in adult male rats on day 9 to induce both renal and testicular toxicity. Key findings: DES significantly attenuated CIS-induced alterations in histopathology and biomarkers. DES resulted in a significant reduction in serum levels of creatinine (Cr), urea, and blood urea nitrogen (BUN), in addition to a marked decrease in urinary levels of albumin and total protein. Additionally, DES efficiently reinstated the oxidative balance by preventing the elevation of malondialdehyde (MDA) and enhancing superoxide dismutase (SOD) activity, and increasing glutathione (GSH) levels. Moreover, DES produced a profound decrease in renal and testicular levels of nucleotide-binding domain-(NOD) like receptor 3 (NLRP3), interleukin (IL)-1β, and caspase-1 when compared to the CIS group. Furthermore, DES significantly decreased CIS-induced elevation in toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) levels in both renal and testicular tissues. Significance: DES can be used as adjuvant therapy with CIS in cancerous cases, pending further clinical studies.

Effect of Oral carnosine supplementation on urinary TGF-\u03b2 in diabetic nephropathy: a randomized controlled trial

BackgroundActivation of the transforming growth factor beta (TGF-β) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-β synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-β levels among patients with diabetic nephropathy.MethodsWe randomly assigned 40 patients with diabetic nephropathy and albuminuria 30–299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-β level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-β.ResultsThe 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-β and renal function measurements. Urinary TGF-β significantly decreased with carnosine supplement (− 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects.ConclusionsThese data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-β level that serves as a marker of renal injury in diabetic nephropathy.Trial registrationThai Clinical Trials, TCTR20200724002. Retrospectively Registered 24 July 2020.

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis.

The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 μg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 μmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.

Organic diet intervention significantly reduces urinary glyphosate levels in U.S. children and adults

BackgroundA growing set of studies show that an organic diet is associated with reduced levels of urinary pesticide analytes. However, with the exception of one pilot study of two individuals, diet intervention studies to date have not analyzed glyphosate, the most commonly used herbicide in the United States and globally. ObjectiveTo investigate the impact of an organic diet intervention on levels of glyphosate and its main metabolite, AMPA (aminomethyl phosphonic acid), in urine collected from adults and children. MethodsWe analyzed urine samples from four racially and geographically diverse families in the United States for five days on a completely non-organic diet and for five days on a completely organic diet (n = 16 participants and a total of 158 urine samples). ResultsMean urinary glyphosate levels for all subjects decreased 70.93% (95% CI -77.96, −61.65, p<0.010) while mean AMPA levels decreased by 76.71% (95% CI -81.54, −70.62, p < 0.010) within six days on an organic diet. Similar decreases in urinary levels of glyphosate and AMPA were observed when data for adults were examined alone, 71.59% (95% CI -82.87, −52.86, p < 0.01) and 83.53% (95% CI -88.42, −76.56, p < 0.01) and when data for children were examined alone, 70.85% (95% CI -78.52, −60.42, p < 0.01) and 69.85% (95% CI -77.56, −59.48, p < 0.01). ConclusionAn organic diet was associated with significantly reduced urinary levels of glyphosate and AMPA. The reduction in glyphosate and AMPA levels was rapid, dropping to baseline within three days. This study demonstrates that diet is a primary source of glyphosate exposure and that shifting to an organic diet is an effective way to reduce body burden of glyphosate and its main metabolite, AMPA. This research adds to a growing body of literature indicating that an organic diet may reduce exposure to a range of pesticides in children and adults.

Decreased levels of urinary liver-type fatty acid-binding protein after switching from tenofovir disoproxil fumarate to tenofovir alafenamide: a prospective observational study.

A single-center, prospective, observational study was conducted between September 2016 and August 2018 in 33 HIV-positive Japanese patients who switched antiretroviral drug regimens from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). The study assessed changes in urinary levels of liver-type fatty acid-binding protein (L-FABP) after switching from TDF to TAF and determined the potential of renal parameters to predict improvement in estimated glomerular filtration rate (eGFR). Median urinary levels of L-FABP were found to be 2.0, 1.4, and 1.3 µg/g creatinine before, at 6 months, and at 12 months after switching to TAF, respectively. The urinary levels of L-FABP, β2 microglobulin (β2MG), and eGFR and the protein-to-creatinine ratio (PCR) were not significantly related to the annual change in eGFR after switching from TDF to TAF. Our results demonstrate a significant decrease in urinary levels of L-FABP after switching from TDF to TAF. However, neither urinary L-FABP, β2MG, PCR, nor eGFR predicted the annual change in eGFR after the change in medication.

Activation of Brown Adipose Tissue Attenuates Diabetic Nephropathy in Mice

Brown adipose tissue (BAT) has been regarded as a potential target organ for the treatment of obesity and related metabolic disorders. However, the protective effect of BAT on type 2 diabetic nephropathy (DN) remains unclear. We aimed to test if BAT activation could prevent the development of DN in mice. Type 2 diabetic mice were induced by streptozotocin (STZ) combined with high-fat diet (HFD). CL 316,243, a β3-adrenergic receptor agonist to activate BAT, was administered intraperitoneally (1mg/kg/day) to diabetic mice for 4 weeks. There were no differences in body weight between the groups. Interestingly, the kidney weight and KW/BW ratio were significantly higher in the DM-Con mice compared with the Con and DM+CL mice (p &amp;lt; 0.01). Treatment with CL 316,243 significantly reduced blood glucose and improved dyslipidemia. Simultaneously, activation of BAT led to marked decreases in urinary levels of albumin and 8-hydroxy-deoxyguanosine (8-OH-dG), suppressed fibrotic and inflammatory cytokine synthesis, and finally ameliorated renal morphological abnormalities. In addition to obviously enhancing BAT activity and white adipose tissue (WAT) catabolism, CL 316,243 significantly increased serum adiponectin and the renal sensitivity to FGF-21. Furthermore, the CL 316,243 treatment reactivated the AMPK-SIRT1-PGC1α signaling pathway in kidneys. These findings suggest that activation of BAT attenuates type 2 DN in mice through both the improvement of systemic metabolism and the renoprotective effect of adipokines. Disclosure M. Guan: None. Y. Cai: None. S. Zou: None.

Expression of renal Oat5 and NaDC1 transporters in rats with acute biliary obstruction.

To examine renal expression of organic anion transporter 5 (Oat5) and sodium-dicarboxylate cotransporter 1 (NaDC1), and excretion of citrate in rats with acute extrahepatic cholestasis. Obstructive jaundice was induced in rats by double ligation and division of the common bile duct (BDL group). Controls underwent sham operation that consisted of exposure, but not ligation, of the common bile duct (Sham group). Studies were performed 21 h after surgery. During this period, animals were maintained in metabolic cages in order to collect urine. The urinary volume was determined by gravimetry. The day of the experiment, blood samples were withdrawn and used to measure total and direct bilirubin as indicative parameters of hepatic function. Serum and urine samples were used for biochemical determinations. Immunoblotting for Oat5 and NaDC1 were performed in renal homogenates and brush border membranes from Sham and BDL rats. Immunohistochemistry studies were performed in kidneys from both experimental groups. Total RNA was extracted from rat renal tissue in order to perform reverse transcription polymerase chain reaction. Another set of experimental animals were used to evaluate medullar renal blood flow (mRBF) using fluorescent microspheres. Total and direct bilirubin levels were significantly higher in BDL animals, attesting to the adequacy of biliary obstruction. An important increase in mRBF was determined in BDL group (Sham: 0.53 ± 0.12 mL/min per 100 g body weight vs BDL: 1.58 ± 0.24 mL/min per 100 g body weight, P < 0.05). An increase in the urinary volume was observed in BDL animals. An important decrease in urinary levels of citrate was seen in BDL group. Besides, a decrease in urinary citrate excretion (Sham: 0.53 ± 0.11 g/g creatinine vs BDL: 0.07 ± 0.02 g/g creatinine, P < 0.05) and an increase in urinary excretion of H(+) (Sham: 0.082 ± 0.03 μmol/g creatinine vs BDL: 0.21 ± 0.04 μmol/g creatinine, P < 0.05) were observed in BDL animals. We found upregulations of both proteins Oat5 and NaDC1 in brush border membranes where they are functional. Immunohistochemistry technique corroborated these results for both proteins. No modifications were observed in Oat5 mRNA and in NaDC1 mRNA levels in kidney from BDL group as compared with Sham ones. Citrate excretion is decreased in BDL rats, at least in part, because of the higher NaDC1 expression. Using the outward gradient of citrate generated by NaDC1, Oat5 can reabsorb/eliminate different organic anions of pathophysiological importance.

Urinary CXCL-10/IP-10 and MCP-1 as markers to assess activity of lupus nephritis

IP-10 and MCP-1 are pro-inflammatory chemokines which are involved in the immunopathogenesis of lupus nephritis and may thus be useful biomarkers. SLE patients fulfilling ACR 1997 criteria were included. SLEDAI was calculated and blood and urine samples collected. Active lupus was defined as SLEDAI ≥4. Active patients were divided into active renal (proteinuria ≥ 500 mg/day or active sediment in urine) and active non-renal lupus. Patients with active renal lupus were followed until the nephritis became inactive, when a second sample was collected. Serum and urinary levels of MCP-1 and IP-10 (pg/ml) were measured by ELISA. Urinary values were normalized for urinary spot creatinine (in mg/dL. Thus the values were expressed as pg/mg creatinine × 100 creatinine). A total of 136 patients with SLE including 78 active (46 active renal and 32 active non-renal) were included. Median age was 25 (10-55) years and SLE duration was 23 (six to 48) months. Both serum (data not shown) and urinary levels of MCP-1 (35.2 (12.7-71.7), 9.4 (4.4-17), p < 0.001) and IP-10 (9.5 (4.4-17.9), 3.9 (1.9-9.3), p < 0.001) were higher in active compared to inactive SLE. However, in active renal compared to active non-renal SLE, there was no difference in serum levels; only urinary levels of MCP-1 (46.2 (19.9-125), 12.7 (5.8-43.9), p < 0.001) and IP-10 (12.5 (5.6-22.7), 5.2 (2.3-12.2), p < 0.05) were higher. On longitudinal follow-up of active renal patients (n = 24), there was a decrease in urinary levels of MCP-1 and IP-10 (p = 0.005). On ROC analysis, urinary MCP-1 outperformed C4 and urinary IP-10, but was similar to dsDNA and C3 in differentiating active renal from non-renal SLE. Urinary and serum IP-10 and MCP-1 are potentially useful markers of lupus activity; however, only the urinary levels are indicative of renal activity. However, on ROC analysis, they are not better than conventional markers.

Renal dopaminergic system activity in rat remnant kidney up to twenty-six weeks after surgery

Aims In 3/4 nephrectomized (3/4nx) rats the renal dopaminergic system was suggested to be involved in the adaptive increase of sodium excretion two weeks after renal mass ablation. The aim of the present study was to evaluate the renal adaptations in sodium handling and renal dopaminergic system activity in 3/4nx rats up to twenty-six weeks after surgery. Main methods The rats were placed in metabolic cages for the collection of 24 h urine for evaluation of sodium, dopamine, dopamine precursor and metabolites. Blood pressure, aromatic L-amino acid decarboxylase (AADC) activity in proximal tubules and the effect of dopamine D 1 receptor selective antagonist (Sch-23390) on natriuresis was evaluated. Key findings A time-dependent increase in both systolic and diastolic blood pressure was observed in 3/4nx rats, and this was accompanied by a decrease in urinary levels of dopamine and in renal AADC activity at twenty-six weeks after renal mass ablation. In contrast to what has been found two weeks after renal mass ablation, the natriuretic response to volume expansion was progressively reduced in 3/4nx rats at ten and twenty-six weeks after surgery and this was accompanied by insensitivity of natriuresis to Sch-23390. Significance In conclusion the renal dopaminergic system activity is compromised in 3/4nx rats in a time-dependent manner after renal mass ablation. It is suggested that this may contribute to compromise sodium excretion and increase blood pressure, in chronic renal insufficiency.

Ibandronate: An IV injection for the treatment for postmenopausal osteoporosis

Intravenous (IV) bisphosphonate dosing for women with postmenopausal osteoporosis is an attractive treatment option where oral therapy is inappropriate because of tolerability or compliance issues. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered by simple IV injection. The optimal dose and interval for this new regimen have been investigated in a detailed clinical trial program. In a pilot study, ibandronate 0.25–2 mg IV every 3 months produced dose-dependent increases in lumbar spine bone mineral density (BMD) at 1 year that were superior to placebo in all but the 0.25 mg group ( P ≤ 0.006). Dose-dependent decreases in urinary levels of C-telopeptide of the α-chain of type I collagen (CTX) were also reported. In a 3-year phase III, antifracture study, dose-dependent gains in BMD and reductions in bone markers with ibandronate 0.5 and 1 mg IV every 3 months were less pronounced than those previously reported for daily oral ibandronate (2.5 mg), and vertebral fracture risk was not significantly different to placebo. However, in a subsequent trial a higher quarterly dose (2 mg) produced greater improvements in BMD and bone turnover markers than both placebo and the 1 mg IV dose. Direct comparison with daily oral ibandronate in the DIVA (Dosing IntraVenous Administration) study showed that gains in lumbar spine BMD with both IV ibandronate doses (2 mg every 2 months and 3 mg every 3 months) were statistically superior to the oral dose (2.5 mg daily) after 1 year ( P < 0.001), with a similar result for total hip and trochanter BMD. Serum CTX concentration was markedly reduced in all groups after 1 year. The overall tolerability profile of IV ibandronate was similar to oral ibandronate, with no evidence of renal toxicity. Influenza-like illness was slightly more common with the IV (5.1% and 4.9% in the 2 mg and 3 mg groups, respectively) than the oral regimen (1.1%) but symptoms were tolerable and primarily associated with the first injection. Ibandronate IV injection administered over 15–30 s can therefore provide superior efficacy to the daily oral regimen for which antifracture efficacy has been demonstrated (62% vertebral fracture risk reduction). Ibandronate is the only IV bisphosphonate licensed for the treatment of postmenopausal osteoporosis and can be conveniently administered at quarterly follow-up visits.

Is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested?

Eight patients with metastatic carcinoid tumor, seven of whom had symptoms of the carcinoid syndrome, were treated with either human leukocyte interferon (seven patients) or recombinant alpha-interferon (IFN alpha-2b) (one patient) at doses of 4.5 to 21 x 10(6) IU weekly for 1 to 21 (mean, 8.5) months. Tumor regression on computed tomography (CT) scan was found in one patient, the CT findings remained unchanged in three, and the tumor progressed in four patients. A clearcut and continuing decrease in urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed in one patient and a transient one in four patients. The symptoms improved in only two of seven patients. Four patients had leukopenia develop, which was circumvented by reducing the dose. The authors conclude that interferon therapy of the carcinoid tumor is not as successful as has been suggested in previous reports.

Effects of Leukocyte Interferon on Clinical Symptoms and Hormone Levels in Patients with Mid-Gut Carcinoid Tumors and Carcinoid Syndrome

We treated nine patients who had carcinoid tumors of the small intestine, six of whom had the carcinoid syndrome, with daily intramuscular doses of leukocyte interferon--3 X 10(6) U per day for one month and 6 X 10(6) U per day for another two months. Seven patients had previously been treated with streptozocin and fluorouracil, without benefit. Treatment with interferon ameliorated the manifestations of the carcinoid syndrome and led to prompt and continuing decreases in urinary levels of 5-hydroxyindoleacetic acid and serum levels of human chorionic gonadotropin subunits and pancreatic polypeptide in all six patients with liver metastases, but it had no clear effect in two of three patients with only lymph-node involvement. After the treatment period, five of the six responders had relapses in clinical manifestations and increases in hormone levels. We conclude that interferon is of benefit in treating metastatic small intestinal carcinoid tumors in patients with the carcinoid syndrome.

The effect of nephrotoxic furans on urinary N-acetyl-glucosaminidase levels in mice

The effects of several potentially nephrotoxic furans on urinary levels of N-acetylglucosaminidase (NAG) were examined to determine whether this test might serve as a useful quantitative index of nephrotoxicity for this series of compounds. Whereas others have found that nephrotoxins such as sodium salicylate and biphenyl cause increases in urinary NAG, we observed that these furans, which were shown to be nephrotoxic by histological procedures, caused significant decreases in urinary levels of the enzyme. This effect was dose-related in the one case examined.

Metabolic studies in a patient with testicular feminization syndrome

The in vitro metabolism of radioactive labeled testosterone and androstenedione by a minced preparation of pubic skin from a patient with the complete testicular feminization syndrome was studied. Double-labeled 5α-dihydrotestosterone and 5α-androstanedione were identified, and 5α-reductase activity was found to be quantitatively similar to that of the pubic skin from a normal subject. The in vivo effect of 5α-dihydrotestosterone-propionate was also studied in this patient with the use of two normal subjects as controls. A sharp decrease in urinary levels of phosphorus and nitrogen was noted in normal subjects, whereas in the patient absence of response to the esterified 5α-reduced testosterone was observed. These results give further support to the concept that the testicular feminization syndrome is not due to a 5α-reductase defect.