Excretion Patterns Research Articles

The Practical Importance of Half-Life in Psychopharmacology.

The half-life of a drug is most commonly defined as the time taken for the plasma or blood level of the drug to fall by half. Elimination half-life, pharmacologic half-life, and biologic half-life are interchangeably used most commonly to describe the half-life of drugs that follow first-order or linear pharmacokinetics; that is, in single-compartment models, where the fall in blood level is proportionate to the concentration of the drug in blood. In 2 compartment models, where the drug equilibrates between blood and (for example) adipose tissue, during elimination there is a sharp initial fall in blood levels followed by a gradual subsequent fall; when drugs display this biphasic elimination pattern, the half-life corresponding to the second phase is what is clinically relevant, and this half-life is known as the terminal half-life. Half-life is influenced by drug distribution, drug metabolism, and drug excretion, each of which can be influenced by many factors such as age, use of concurrent medications, and presence of liver or renal disease. In order to maintain uniform blood levels and reduce the adverse effect risk, drugs with short half-lives need to be dosed more frequently. Drugs with short half-lives are more likely to be associated with withdrawal or discontinuation syndromes. The duration of action of a drug, time to steady state levels, and time to washout are each influenced by the value of the drug half-life. All these terms and concepts are defined and explained with the help of clinically relevant examples. Mental health care professionals who prescribe to patients need to know the half-lives of the drugs that they prescribe, the half-lives of active metabolites, if any, how these half-lives may differ with individual patient characteristics, and how to use this knowledge to prescribe to best advantage.

Toxicity mitigation and biodistribution of albumin corona coated graphene oxide and carbon nanotubes in Caenorhabditis elegans

In this work, the toxicity and biodistribution of graphene oxide (GO) and oxidized multi-walled carbon nanotubes (MWCNT) were investigated in Caenorhabditis elegans. Bovine serum albumin (BSA) was selected as a model protein to evaluate the influence of protein corona formation on materials physicochemical properties, colloidal stability, and toxicity. Biological assays were performed to assess the effects of bare and albumin corona coated materials on survival, oxidative stress, intestinal barrier permeability, growth, reproduction, and fertility. Critical alterations in topography, surface roughness and chemistry of GO and MWCNT were observed due to albumin corona formation. These modifications were associated with changes in colloidal stability of materials and prevention of their aggregation and sedimentation in nematode testing medium. Both GO and MWCNT caused damage to nematode survival, growth, reproduction, and fertility, as well as enhanced oxidative stress and permeability of the intestinal barrier. But GO was more toxic than MWCNT to C. elegans, especially at long-term assays. Albumin corona mitigated 100% of acute and chronic effects of MWCNT. In contrast, the negative effects of GO were not completely mitigated; GO inhibited 16.2% of nematode growth, 86.5% of reproduction, and 32.0% of fertility at the highest concentration evaluated (10 mg L−1), while corona coated GO mitigated 50% and 100% of fertility and growth, respectively. Confocal Raman spectroscopy imaging was crucial to point out that bare and albumin corona coated GO and MWCNT crossed the C. elegans intestinal barrier reaching its reproductive organs. However, BSA corona protected the nematodes targeted organs from negative effects from MWCNT and blocked its translocation to other tissues, while coated GO was translocated inside the nematode affecting the functionality of crucial organs. In addition, coated MWCNT was excreted after 2 h of food resumption, whereas coated GO still accumulated in the nematode intestine. Our results demonstrate that the materials different translocation and excretion patterns in C. elegans had a relation to the impaired physiological functions of primary and secondary organs. This work is a contribution towards a better understanding of the impacts of protein corona on the toxicity of graphene oxide and carbon nanotubes; essential information for biological applications and nanosafety.

A triple threat: Ocean warming, acidification, and rare earth elements exposure triggers a superior antioxidant response and pigment production in the adaptable Ulva rigida

• La and Gd were accumulated in 24 h. • Elimination of La and Gd did not occur in U. rigida . • La and Gd showed different accumulation and elimination patterns in future predicted scenarios. • La and Gd triggered an efficient antioxidant defence response in U. rigida . • REE and climate change exposure requested a superior antioxidant response. Anthropogenic increased atmospheric CO 2 concentrations will lead to a drop of 0.4 units of seawater pH and ocean warming up to 4.8°C by 2100. Contaminant's toxicity is known to increase under a climate change scenario. Rare earth elements (REE) are emerging contaminants, that until now have no regulation regarding maximum concentration and discharge into the environment and have become vital to new technologies such as electric and hybrid-electric vehicle batteries, wind turbine generators and low-energy lighting. Studies of REE, namely Lanthanum (La) and Gadolinium (Gd), bioaccumulation, elimination, and toxicity in a multi-stressor environment (e.g., warming and acidification) are lacking. Hence, we investigated the algae phytoremediation capacity, the ecotoxicological responses and total chlorophyll and carotenoid contents in Ulva rigida during 7 days of co-exposure to La or Gd (15 µg L −1 or 10 µg L −1 , respectively), and warming and acidification. Additionally, we assessed these metals elimination, after a 7-day phase. After one day of experiment La and Gd clearly showed accumulation/adsorption in different patterns, at future conditions. Unlikely for Gd, Warming and Acidification contributed to the lowest La accumulation, and increased elimination. Lanthanum and Gd triggered an adequate activation of the antioxidant defence system, by avoiding lipid damage. Nevertheless, REE exposure in a near-future scenario triggered an overproduction of ROS that requested an enhanced antioxidant response. Additionally, an increase in total chlorophyll and carotenoids could also indicate an unforeseen energy expense, as a response to a multi-stressor environment.

Environmental risk and possibilities of ciprofloxacin phytoremediation

The article considers antibiotics of the quinolone series, their using and mechanism of action. Based on the literature data, their application, distribution mechanisms, accumulation and behavior in environmental objects are considered. It is noted that the role of aquatic plants in the processes of biochemical degradation has not been sufficiently studied. Under the conditions of a laboratory model experiment, we studied the patterns of ciprofloxacin elimination by hydatophytes, i.e., aquatic plants completely submerged in water (Canadian pondweed, rigid hornwort, Eurasian watermilfoil). The spectral characteristics of ciprofloxacin were studied and quantitative estimates of the absorption of the antibiotic from solutions with submerged aquatic plants were made. We calculated elimination rate constants and phytoremediation potential. It was found that the rate of elimination of ciprofloxacin and phytoremediation potential depended on the type of aquatic plant and the initial concentration of the antibiotic. The highest elimination rate was found in models containing hornwort. Based on the data obtained, a conclusion was made about the prospects for the using of hydatophytes in phytopurification systems for post-treatment of wastewater from ciprofloxacin.

Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis.

Endogenous and exogenous metabolite concentrations may be susceptible to variation over time. This variability can lead to misclassification of exposure levels and in turn to biased results. To assess the reproducibility of metabolites, the intraclass correlation coefficient (ICC) is computed. A literature search in three databases from 2000 to May 2021 was conducted to identify studies reporting ICCs for blood and urine metabolites. This review includes 192 studies, of which 31 studies are included in the meta-analyses. The ICCs of 359 single metabolites are reported, and the ICCs of 10 metabolites were meta-analyzed. The reproducibility of the single metabolites ranges from poor to excellent and is highly compound-dependent. The reproducibility of bisphenol A (BPA), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), methylparaben, and propylparaben is poor to moderate (ICC median: 0.32; range: 0.15-0.49), and for 25-hydroxyvitamin D [25(OH)D], it is excellent (ICC: 0.95; 95% CI, 0.90-0.99). Pharmacokinetics, mainly the half-life of elimination and exposure patterns, can explain reproducibility. This review describes the reproducibility of the blood and urine exposome, provides a vast dataset of ICC estimates, and hence constitutes a valuable resource for future reproducibility and clinical epidemiologic studies.

Effects of three feeding strategies (self‐feeders, automatic feeding and apparent satiety) on growth performance, haematological parameters, waste excretion and feed cost in Amazonian fish ( Colossoma macropomum )

A 127-day experiment was conducted to evaluate the effect of feeding strategies on juvenile tambaqui's (Colossoma macropomum) growth, body composition, haematological and biochemical parameters, excretion pattern and economic indices. Fifteen tanks randomly stocked 150 juvenile tambaqui (82.0 ± 0.8 g, mean ± SEM) subjected to three feeding strategies (n = 5): self-feeder system (T1); automatic-feeding with three set meals/day (T2) and apparent satiety with three meals/day (T3). The results revealed that fish T1 and T3 showed the best feed intake, feed conversion ratio, protein efficiency ratio and protein retention rate (p < 0.05). However, no significant differences were observed in growth, survival, haematological parameters, body composition and total ammonia nitrogen excretion among treatments (p > 0.05). Cortisol obtained a significantly higher value for fish T3 (122.92 ± 5.75 ng/ml), with a low water phosphorus value for fish T1 (0.43 ± 0.06 mg/L). Lastly, the feed cost based on the values deriving from diets revealed better indices (variable cost, unitary contribution margin and contribution margin index) for fish T1 and T3. In short, our findings suggest the benefits of using self-feeders for tambaqui aquaculture.

High value of 64Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson’s disease

Wilson’s disease (WD) is an inherited disorder of copper metabolism associated with mutations in ATP7B gene. We have shown that the administration of an adeno-associated vector (AAV) encoding a mini version of human ATP7B (VTX-801) provides long-term correction of copper metabolism in a murine WD model. In preparation of a future clinical trial, we have evaluated by positron emission tomography (PET) the value of 64Cu biodistribution, excretion pattern, and blood kinetics as pharmacodynamic biomarkers of VTX-801 effects. Six-week-old WD mice were injected intravenously with increasing doses of VTX-801 and 3 weeks or 3 months later with [64Cu]CuCl2. Untreated WD and wild-type (WT) mice were included as controls. Control WD mice showed increased hepatic 64Cu retention, reduced fecal excretion of the radiotracer, and altered 64Cu blood kinetics (BK) compared with WT mice. VTX-801 treatment in WD mice resulted in a significant reduction of hepatic 64Cu accumulation, the restoration of fecal 64Cu excretion, and the correction of 64Cu BK. This study showed that VTX-801 restores physiological copper metabolism in WD mice, confirming the mechanism of action of VTX-801, and demonstrated the translational potential of [64Cu]CuCl2-PET to explore VTX-801 pharmacodynamics in a minimally invasive and sensitive manner in WD patients.

&lt;br/&gt; IMPACTO DA OBSTIPAÇÃO NO DOENTE CRÍTICO: Revisão Sistemática da Literatura &lt;br/&gt;

Objective: Map available evidence on the effects of constipation on the health of the critical patient. Methods: A scoping review based on the JBI criteria was performed to answer the PCC question: What evidence is available on the effects of constipation on the health of critical patients admitted to intensive care? The electronic search was conducted in a single phase in August 2021, using the EBSCOhost platform, applying the health descriptors combined with the Booleans “AND” and “NOT”, in the sequence: “constipation” “AND” “Critical Care” “AND” “Patients” “NOT” “child*” “NOT” “animals”. Results: From the 330 available studies, we selected only 5, which met the predefined criteria. It was found that constipation is a problem with high incidence in critically ill patients and related to multiple factors. Treatment may be pharmacological or nonpharmacological. Conclusions : Early detection and treatment is recommended. The nurse plays an essential role in the patient assessment, in recording bowel elimination patterns, as well as in the institution of preventive measures and patient treatment. There was no reference to the length of stay, or the benefit of early rising. A reduction in the risk of constipation associated with the use of omeprazole or ranitidine was observed, but further studies are suggested. Keywords: Constipation; Critical Care; Patients; Drug Therapy; Non-pharmacological treatment.

Chronic Circadian Disruption Contributes to Excess Aldosterone Production and Loss of Diurnal Electrolyte Excretion

Disruptions in circadian rhythms contribute to a number of cardiometabolic health risks, including kidney disease. While chronic circadian disruption (CCD) has been recognized as a health risk in a number of other organ systems, we do not understand the effects of CCD on kidney function and sodium handling factors. Individuals with CCDs such as rotating shift workers, have an increased incidence of kidney and cardiovascular disease including impaired sodium excretion patterns. We hypothesized that this impaired sodium excretion is due in part to increased activation of the renin‐aldosterone‐angiotensin system (RAAS). We recently observed that CCD interrupts blood pressure, heart rate, and activity rhythms. Male 8‐week‐old C57BL/6J mice were placed under either a normal 12:12 light/dark cycle (control) protocol or a 10:10 light/dark cycle (CCD, T20) protocol, each with ad libitum food and water for 12 weeks. Previous experiments with this model have demonstrated that after 10 weeks the T20 mice did not exhibit a significant difference in mean arterial pressure (MAP) between the light and dark cycles (114±13mmHg during dark cycle, 113±12mmHg during light cycle, p=0.86) as opposed to control animals, who did display a typical circadian pattern in MAP averaging 119±3 mmHg during the dark cycle and 101±2 mmHg during the light cycle (p&gt;0.001). The same pattern persisted in the heart rate (HR) of these animals, with the T20 animals lacking a diurnal variation in HR (537±14 BPM during dark cycle, 526±5 BPM during light cycle, p=0.48), and the control animals maintaining a dark/light period difference (584±11 BPM during dark cycle, 511±4 BPM during light cycle, p=0.001). Prior studies indicate that the circadian timing system controls sodium reabsorption throughout the nephron by effecting aldosterone effects on collecting duct sodium transport systems via the molecular clock. Therefore, aldosterone excretion was assayed in urine from control(n=6) and T20 mice (n=4). Interestingly, T20 animals excreted an order of magnitude more aldosterone than control animals (p&lt;0.015 2‐way ANOVA) and lacked a diurnal variation in aldosterone excretion (115.1±51.5 µg/hr during the dark cycle, 64.1±13.1 µg/hr during the light cycle, p=0.17 dark v. light) and during both dark and light phases (0.080±0.014 µg/hr and 0.012±0.003 µg/hr, respectively, p=0.02 dark v. light). T20 mice also lacked a diurnal variation in sodium (UNaV) and potassium (UKV) excretion as compared to control mice. These results suggest that CCD disrupts diurnal sodium handling, at least in part, by disruptions in the RAAS. We further propose that the loss of blood pressure rhythms may be due to hyperaldosteronism in CCD mice.

Liquid Contact Ion Selective Electrode Green Method for the Determination of Flavoxate HCl Main Active Metabolite in Pure Powder and Human Urine with Establishment of Urinary Excretion Pattern

The main aim of this work is to develop the first liquid contact ion selective electrode potentiometric method for determination of flavoxate HCl main metabolite; 3-methylflavone-8-carboxylic acid (MFC). The method can be used for studying flavoxate HCl bioavailability through tracing its active metabolite; MFC, excreted in human urine. The metabolite was determined in pure powder and in human urine with establishment of urinary excretion pattern without any sample extraction or pretreatment procedures. The suggested sensor's performance was assessed in accordance with IUPAC guidelines. According to the Bioanalytical Method Validation Guidance for Industry, the suggested method was validated where good results were obtained. The proposed method is an excellent green eco-friendly analytical method.

Fish Feeds in Aquaponics and Beyond: A Novel Concept to Evaluate Protein Sources in Diets for Circular Multitrophic Food Production Systems

With the general objective of optimizing internal nutrient recycling, circular multitrophic food production systems, e.g., combining fish, plant, and insect larvae production, rely on the quality and composition of sustainable nutritional inputs. Therefore, differences in dissolved and solid nutrient excretion patterns produced by Nile tilapia (Oreochromis niloticus) reared in recirculating aquaculture systems (RAS) with 5% daily water exchange and fed black soldier fly meal (BSFM), poultry by-product meal (PM), poultry blood meal (PBM) and fish meal (FM) as single protein sources were investigated to evaluate the potential for creating specific fish meal-free diets. Fish fed the FM and PM diet showed the significantly best (p &lt; 0.05) and among each other similar (p &gt; 0.05) growth performance (specific growth rate (SGR): 2.12 ± 0.04/2.05 ± 0.11; feed conversion ratio (FCR): 0.86 ± 0.03/0.92 ± 0.01), whereas the PBM diet caused significantly reduced performance (SGR: 1.30 ± 0.02; FCR: 1.79 ± 0.05) in comparison to the FM/PM diet as well as the BSF diet (SGR: 1.76 ± 0.07; FCR: 1.11 ± 0.05). The FM and PM diet resulted in a faster increase and significantly higher dissolved nitrogen and phosphorus levels, while the BSF diet caused faster accumulation and significantly elevated levels of dissolved potassium, magnesium, and copper. The PBM diet resulted in the feces with the significantly highest nutrient density (gross energy, crude protein, and amino acids) but overall much lower dissolved nutrient levels in the water. Results are discussed with regard to implications for developing circular multitrophic food production systems.

Urine and fecal excretion patterns of dairy cows divergent for milk urea nitrogen breeding values consuming either a plantain or ryegrass diet

Environmental degradation has been attributed to inefficient nitrogen utilization from pastoral dairy production systems. This degradation has especially been associated with the urine patch, which has been identified as a key component of nitrate leaching to waterways. However, a lack of information exists regarding the pattern of urination events and individual urination characteristics across the day, which would help inform strategic management decisions. The aim of this study was therefore to evaluate and report the patterns and characteristics of fecal and urination events throughout the day for cows divergent for milk urea nitrogen breeding values (MUNBV) on either a plantain [Plantago lanceolata L. (PL)] or ryegrass [Lolium perenne L. (RG)] diet as ways to reduce environmental impact. Sixteen multiparous lactating Holstein Friesian × Jersey cows divergent for MUNBV were housed in metabolism crates for 72 h, with all excretion events captured and analyzed. Cows selected as low for MUNBV consistently had a 65.2-kg lower urinary urea nitrogen (UUN) load (kg/ha) than high MUNBV cows for all hours of the day when consuming RG. The association between lower urinary urea loading rates and less N leaching implies a reduced environmental impact from low MUNBV cows consuming RG. When cows consumed PL, regardless of MUNBV, they had on average a 137.5-kg (UUN/ha) lower loading rate compared with high MUNBV cows on RG and a 72.2-kg (UUN/ha) lower loading rate compared with low MUNBV cows consuming RG across the day. Cows on PL also exhibited a different diel pattern of UUN load compared with cows consuming RG. Differences in the diel pattern of N excreted in feces were also detected based on MUNBV and by diet, with low MUNBV cows excreting on average 3.06 g more N in feces per event for the majority of the day compared with high MUNBV cows when consuming RG. Lower UUN loading rates and more N excreted in feces indicate a potentially lower environmental impact from low MUNBV cows when consuming RG compared with high MUNBV cows. The use of the PL diet also resulted in lower UUN loading rates and greater levels of N excreted in feces compared with RG, therefore also indicating its ability to reduce environmental impact compared with RG.

In Vitro and In Vivo Metabolism of a Novel Antimitochondrial Cancer Metabolism Agent, CPI-613, in Rat and Human.

CPI-613, an inhibitor of pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) enzymes, is currently in development for the treatment of pancreatic cancer, acute myeloid leukemia, and other cancers. CPI-613 is an analog of lipoic acid, an essential cofactor for both PDH and KGDH. Metabolism and mass balance studies were conducted in rats after intravenous administration of [14C]-CPI-613. CPI-613 was eliminated via oxidative metabolism followed by excretion of the metabolites in feces (59%) and urine (22%). β-Oxidation was the major pathway of elimination for CPI-613. The most abundant circulating components in rat plasma were those derived from β-oxidation. In human hepatocytes, CPI-613 mainly underwent β-oxidation (M1), sulfur oxidation (M2), and glucuronidation (M3). The Michaelis-Menten kinetics (Vmax and Km) of the metabolism of CPI-613 to these three metabolites predicted the fraction metabolized leading to the formation of M1, M2, and M3 to be 38%, 6%, and 56%, respectively. In humans, after intravenous administration of CPI-613, major circulating species in plasma were the parent and the β-oxidation derived products. Thus, CPI-613 metabolites profiles in rat and human plasma were qualitatively similar. β-Oxidation characteristics and excretion patterns of CPI-613 are discussed in comparison with those reported for its endogenous counterpart, lipoic acid. SIGNIFICANCE STATEMENT: This work highlights the clearance mechanism of CPI-613 via β-oxidation, species differences in their ability to carry out β-oxidation, and subsequent elimination routes. Structural limitations for completion of terminal cycle of β-oxidation is discussed against the backdrop of its endogenous counterpart lipoic acid.

Following the route of veterinary antibiotics tiamulin and tilmicosin from livestock farms to agricultural soils

Veterinary antibiotics (VAs) are not completely metabolized in the animal body. Hence, when animal excretes are used as soil manures, VA residues are dispersed with potential implications for environmental quality and human health. We studied the persistence of tiamulin (TIA) and tilmicosin (TLM) along their route from pig administration to fecal excretion and to agricultural soils. TLM was detected in feces at levels folds higher (4.27–749.6 μg g-1) than TIA (0.55–5.99 μg g-1). Different administration regimes (feed or water) showed different excretion patterns and residual levels for TIA and TLM, respectively. TIA and TLM (0.5, 5 and 50 μg g-1) dissipated gradually from feces when stored at ambient conditions (DT50 5.85–35.9 and 23.5–49.8 days respectively), while they persisted longer during anaerobic digestion (DT90 >365 days) with biomethanation being adversely affected at VA levels > 5 μg g-1. When applied directly in soils, TLM was more persistent than TIA with soil fumigation extending their persistence suggesting microbial degradation, while soil application through feces increased their persistence, probably due to increased sorption to the fecal organic matter. The use of TIA- and TLM-contaminated feces as manures is expected to lead to VAs dispersal with unexplored consequences for the environment and human health.

The stress, salt excretion, and nighttime blood pressure (SABRE) study: Rationale and study design

BackgroundAbnormal diurnal patterns of blood pressure (BP) on ambulatory BP monitoring (ABPM), defined by reduced BP dipping or elevated nighttime BP, are associated with increased risk for adverse cardiovascular events. Psychological stress is associated with abnormal diurnal patterns of BP. Exposure to an acute stressor (e.g., mental stress task) normally increases urinary sodium excretion. However, some individuals have sodium retention after stress provocation, revealing substantial between-person variability in the degree of stress-induced sodium excretion. Prior research suggests urinary sodium excretion that does not occur during the daytime may shift toward the nighttime, accompanied by an increase in nighttime BP. Associations between psychological stress and the diurnal patterns of sodium excretion and BP are not yet fully understood. DesignThe study is conducted in both the laboratory and naturalistic environment with a multi-racial/ethnic sample of 211 healthy adults. In the laboratory, change in urinary sodium excretion in response to mental stress tasks is examined with pre-/post-stress assessments of sodium excretion. Changes in angiotensin-II, catecholamines, BP, heart rate, endothelin-1, and cortisol are also assessed. In the 24-hour naturalistic environment, the diurnal patterns of sodium excretion and systolic BP are assessed as daytime-to-nighttime ratio of sodium excretion and ABPM, respectively. Ecological momentary assessments of perceived stress are also collected. SummaryThe SABRE study investigates previously unexplored associations between stress-induced urinary excretion in the laboratory, diurnal patterns of sodium excretion and BP in the naturalistic environment, and ecological stress. It has high potential to advance our understanding of the role of psychological stress in hypertension.

Studies on urinary excretion and variability of dietary iodine in healthy Japanese adults.

The daily consumption of iodine in Japan is higher than in most countries, and there are few reports on iodine metabolism and variance of habitual iodine ingestion in an iodine-sufficient area. To elucidate the patterns of short-term urinary iodine excretion (UIE) and long-term variability of habitual iodine intake, the urinary iodine excretion process after a high dietary iodine load of 3 mg was observed in eight Japanese adults under strict supervision with complete urine collections for three days. In addition, estimated UIE and dietary iodine intake (DII) were assessed in 24 university students using repeated spot urine samples of ten consecutive days and a food frequency questionnaire in each of the four seasons. Approximately 50, 75 and 90% of orally ingested iodine was excreted into the urine at 8, 13 and 22 hours after ingestion, respectively. Almost an equal amount of ingested iodine in meals was cleared within 33.5 h after eating with a maximum excretion rate at 3-4 h. There was a high fluctuation in the UIE and DII in the university students. The intra- and inter-individual crude coefficients of variation were 123 or 294.7% for UIE, and 58.3 or 88.7% for DII, respectively, indicating a higher variance of habitual iodine intake than in other countries. The frequency of occurrence for UIE above 3 mg was every 43 days. Rapid renal clearance of iodine and high variability as well as low frequency of dietary iodine intake might prevent people from being exposed to an excess iodine intake over the long term in Japan.

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD.

Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to ESKD. Urinary sediment podocin (u-sed Pod) mRNA excretion and urinary supernatant podocalyxin (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases. From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (n=15 patients with minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n=15 with minimal change nephrotic syndrome [MCNS], n=15 with membranous nephropathy [MN], n=60 with IgA nephropathy [IgAN], n=19 with crescentic GN [Cres GN], n=10 with lupus nephritis [LN], and n=38 with other kidney diseases). We examined u-sed Pod mRNA excretion, u-sup PCX protein, and the urinary protein-creatinine ratio (u-PCR). u-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (r=0.37, P<0.001). Both u-sed Pod mRNA excretion and u-sup PCX protein were significantly correlated with u-PCR (r=0.53, P<0.001 and r=0.35, P<0.001, respectively). Interestingly, u-sed Pod mRNA excretion was significantly increased in proliferative-type GN-including IgAN with extracapillary proliferative lesions, Cres GN, and LN class IV-and significantly correlated with the rate of crescent formation, whereas u-sup PCX protein was significantly increased only in those with MN and subepithelial dense deposit-type LN compared with controls. Higher u-sed Pod mRNA excretion and u-sup PCX protein were associated with proliferative-type GN, indicating podocyte detachment and subepithelial dense deposit-type GN, respectively. The results suggest that u-sed Pod mRNA excretion and u-sup PCX protein have usefulness for the diagnosis and measurement of disease activity with regard to glomerular diseases.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Effect of Nursing Instructions on Reducing Selected Functional Gastrointestinal Disorders among Elderly Patients

Aim of the study: To evaluate the effect of the nursing instructions on reducing the selected functional gastrointestinal disorders among elderly patients. Research design: Quasi-experimental (Pre–posttest). A consecutive sample of one hundred elderly patients was included in this study. Setting: The current study was carried out at a Geriatric home, Geriatric club, and Gastrointestinal clinic at Qena two tools were utilized to collect data, First Tool: A Structured interviewing questionnaire sheet, personal data (age, gender, marital status level, etc.)Second Tool: The Patient Assessment of Constipation-Symptoms questionnaire. Results: there was a highly statistically significant difference in total mean average score and SD (20.4 ±8.3, 10.8 ±8.3) of constipation symptoms severity during pre and post-nursing instructions implementation p value≤0.05. Conclusion implementing the nursing instructions regarding selected functional gastrointestinal disorders among elderly patients reflected a significant impact on patient's outcomes of constipation this significant difference justified the research hypothesis. Recommendations: A continuous education and training are offered on regular basis for elderly patients regarding gastrointestinal disorders, in addition to educational classes for elderly people about age-related changes that affect their gastrointestinal tract and elimination pattern without a feeling of shame or embarrassment to prevent complications. Encouraging to improve the elderly home foods menu to contain high fiber foods such as vegetables and fruits to over com constipation problems

Urinary androgens excretion patterns and prostate cancer in Mexican men.

Epidemiological studies related to androgens and prostate cancer (PC) have focused on serum determination of testosterone, androstenedione (A4), and DHEA, with inconsistent results. Herein, we hypothesized that differences in androgen biosynthetic and metabolic pathways, rather than differences in specific androgen concentrations, are associated with prostatic carcinogenesis. Therefore, spot urine samples from 111 incident PC cases with Gleason score at diagnosis and 227 healthy population controls, were analyzed. Urinary androgen concentrations (nanograms/milligrams of creatinine) were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Using a factor analysis, we identified three androgen urinary excretion patterns. In a subsample, we evaluated a modification effect of the androgen receptor (AR) CAG polymorphism. Pattern I, characterized by A4 and testosterone hydroxylated metabolites (11β-OHT; 2β-OHT; 15β-OHT; 2α-OHT; 6β-OHT), was associated with high PC odds among carriers of AR gene (CAG)>19 repeats (OR: 3.67 95% CI: 1.23-11.0; P for interaction= 0.009). Conversely, higher testosterone excretion (pattern III), was marginally associated with lower (OR: 0.35 95% CI: 0.12-1.00, P for trend= 0.08) poorly differentiated PC (Gleason ≥8). No clear association was observed with pattern II (DHEA; 16α and 16β-OHT). Our results were consistent with the previous evidence which suggests that the C11-oxy backdoor pathway is important for prostatic carcinogenesis. Androgen urine excretion analysis could be useful for PC diagnosis, treatment, and prognosis; however, further studies with a larger number of samples and the urinary determination of 11-ketoandrogens are necessary.