Amount Of Urinary Excretion Research Articles

A urinary biomarker for monitoring exposures to 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate in rats.

2,2,4-Trimethyl-1,3-pentanediol monoisobutyrate (TMPD-MB) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TMPD-DB) are widely used primarily as surface stabilizers for water-based paints and plasticizers, respectively. Exposure to these compounds has been suspected as being associated with sick building syndrome and allergic diseases such as asthma in general populations. Therefore, it is very important to be able to know the amounts of these compounds absorbed into the body in order to evaluate its adverse effects on humans in living environments. In the present study, the urinary excretion kinetics of TMPD-MB and TMPD-DB were studied in animals to establish for urinary metabolites suitable as biomarkers for monitoring exposure. A single dose (48-750mg/kg body weight) of TMPD-MB or TMPD-DB was administered intraperitoneally to male Sprague-Dawley rats, and their urine was collected periodically for a week. Two major metabolites, 2,2,4-trimethyl-1,3-pentanediol (TMPD) and 3-hydroxy-2,2,4-trimethylvaleric acid (HTMV), were measured in the urine samples. Their kinetics were evaluated by moment analysis of the urinary excretion rates of the metabolites versus time curves. The urinary excretion amounts of HTMV were suggested to be proportional to the absorption amounts over a wide exposure range of both TMPD-MB and TMPD-DB. The amounts of HTMV accounted for almost the same level, i.e., 4-5% of the dose at the lowest dosage, in rats tested for both TMPD-MB and TMPD-DB. Urinary HTMV was considered to be an optimal biomarker for monitoring exposure to mixtures of these compounds.

Comparison of amikacin lung delivery between AKITA® and eFlow rapid® nebulizers in healthy controls and patients with CF: A randomized cross-over trial

IntroductionNebulization plays a key role in the treatment of cystic fibrosis. The Favorite function couple to jet nebulizers (AKITA®) emerged recently. The aim of this study was to assess the efficiency of the lung delivery by the AKITA® by comparing the urinary concentration of amikacin after nebulization with the AKITA® and the eFlow rapid®, in healthy subjects and patients with CF (PwCF). MethodThe two samples (healthy subjects and PwCF) were randomized (cross-over 1:1) for two nebulizations (500 mg of amikacin diluted in 4 mL of normal saline solution), with the AKITA® and with the eFlow rapid®. The primary endpoint was the amount of urinary excretion of amikacin over 24 h. The constant of elimination (Ke) was calculated based on the maximal cumulative urinary amikacin excretion plotted over time. ResultsThe total amount of urinary amikacin excretion was greater when AKITA® was used in PwCF (11.7 mg (8.2–14.1) vs 6.1 mg (3.7–13.3); p = 0.02) but not different in healthy subjects (14.5 mg (11.7–18.5) vs 12.4 mg (8.0–17.1); p = 0.12). The duration of the nebulization was always shorter with eFlow rapid® than with AKITA® (PwCF: 6.5 ± 0.6 min vs 9.2 ± 1.8 min; p = 0.001 – Healthy: 4.7 ± 1.3 min vs 9.7 ± 1.6 min; p = 0.03). The constant of elimination was similar between the two modalities in CF subjects (0.153 (0.071–0.205) vs 0.149 (0.041–0.182); p = 0.26) and in healthy subjects (0.166 (0.130–0.218) vs 0.167 (0.119–0.210), p = 0.25). Conclusionthe Favorite inhalation is better to deliver a specific amount of drug than a mesh nebulizer (eFlow rapid®) in PwCF but not in healthy subjects.

878-P: Absolute Amount of Urinary Glucose Excretion, Not the Change, Is the Measure Determinant for the Effects of SGLT2 inhibitors

SGLT2 inhibitors exhibit hypoglycemic effect via increased urinary glucose excretion (UGE) by inhibiting glucose reabsorption in the kidney. Although the effects of SGLT2 inhibitors are theoretically dependent on UGE, clinical trials have shown renoprotective effect even in severely impaired kidney function. Thus, we aimed to investigate the relationship between UGE and various parameters before and after the administration of SGLT2 inhibitors. The patients newly administered SGLT2 inhibitors and measured 24-hour UGE before and after the administration during hospitalization for diabetes education were included. Body weight (BW), blood ketone levels, hematocrit (Ht), eGFR, and 7-point SMBG (DBG) were measured, and the correlations between the parameters before(b-), after (a-) and the change (Δ-) were analyzed by simple linear regression. A total of 32 patients (age 59.3±10.9 years, 19 males) were included (empagliflozin 5, tohogliflozin 6, dapagliflozin 2, canagliflozin 4, luseogliflozin 15). The mean A1C and BW were 8.8±1.2% and 77.7±11.5kg, and mean UGE, average of DBG at baseline were 15.4 ± 27.5g/day and 10.3±2.0mM/L, respectively. As shown in table, ΔDBG showed correlation only with UGE before and after administration but not with ΔUGE. In conclusion, hypoglycemic effect of SGLT2 inhibitors is dependent on absolute amount of UGE but not on ΔUGE after administration. Disclosure Y.Hamamoto: None. Y.Yamada: Speaker's Bureau; Novo Nordisk Pharma Ltd., Teijin Pharma Limited, Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd. Y.Seino: Research Support; Terumo Corporation, Nippon Boehringer Ingelheim, Arkray Marketing, Taisho Pharmaceutical Holdings Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Speaker's Bureau; Merck & Co., Inc., Nippon Boehringer Ingelheim, Arkray Marketing, Taisho Pharmaceutical Holdings Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd.

#4942 GENOTYPE-PHENOTYPE ANALYSIS IN FAMILIAL RENAL GLUCOSURIA PATIENTS: THE CRUCIAL ROLE OF CONSERVED RESIDUES

Abstract Background and Aims Familial renal glucosuria (FRG) is a hereditary disorder caused by mutations in SLC5A2, the gene encoding sodium-glucose cotransporter 2 (SGLT2) in proximal tubule cells. In this study, we aimed to characterize the genotype-phenotype relationship in FRG patients using data from our cohort and literature review. Method We sequenced SLC5A2 in a cohort of 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients using urinary glucose excretion in a 4-hour oral glucose tolerance test (OGTT). We built an open-source online calculator to facilitate the calculation of RTG. Besides, we reviewed published literature and obtained information on SLC5A2 variants and 24-hour urinary glucose (24hUG) in FRG patients. Results We identified 27 rare SLC5A2 variants, including 13 novel variants (G484D, R564W, A212S, c.574+1G>C, W649*, S592Cfs*6, Q579*, A89T, Y339*, V39F, G491E, A464E, and G360D), in our cohort and yielded 107 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2mmol/L. Patients carrying two SLC5A2 variants had lower RTG (3.9 vs. 6.2 mmol/L, p = 0.057) and larger amounts of 24-hour urinary glucose excretion (24hUG) (52.39 vs. 7.20 g/1.73m2, p = 2.7*10−8) than those carrying a single variant. Patients with homozygous missense or in-frame indels had mean 24hUG of 82.30g/1.73m2, comparable to those with homozygous truncating variants (81.66g/1.73m2) and significantly more than those with homozygous splicing variants (35.38g/1.73m2, p = 0.026). Patients with homozygous missense variants involving conservative residues had more 24hUG (104.76g/1.73m2) than those with variants at non-conservative residues (46.37g/1.73m2, p = 0.0031). Conclusion We built a comprehensive map showing the impact of SLC5A2 variant type, variant location, and zygosity on glucosuria severity. Our results highlighted that conserved residues play an essential role in maintaining the transport function of SGLT2.

Non-dipping pulse rate and chronic changes of the kidney in patients with chronic kidney disease.

An insufficient decrease in nocturnal pulse rate (PR), non-dipping PR, reflects autonomic imbalance and is associated with cardiovascular events and all-cause mortality. We aimed to investigate the clinical and microanatomical structural findings associated with the non-dipping PR status in patients with chronic kidney disease (CKD). This cross-sectional study included 135 patients who underwent ambulatory blood pressure monitoring and kidney biopsy concurrently at our institution between 2016 and 2019. Non-dipping PR status was defined as (daytime PR-nighttime PR)/daytime PR <0.1. We compared clinical parameters and microstructural changes in the kidney between patients with and without non-dipping PR, including 24 h proteinuria, glomerular volume, and Mayo Clinic/Renal Pathology Society Chronicity Score. The median age was 51 years (interquartile range: 35-63), 54% of which were male, and the median estimated glomerular filtration rate was 53.0 (30.0-75.0) mL/min/1.73 m2. Non-dipping PR status was observed in 39 patients. Patients with non-dipping PR were older and had worse kidney function, higher blood pressure, greater prevalence of dyslipidemia, lower hemoglobin levels, and a larger amount of urinary protein excretion than patients with dipping PR. Patients with non-dipping PR had more severe glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis. In the multivariable analysis, the severe chronic changes of the kidney were associated with non-dipping PR status after adjusting for age, sex, and other clinical parameters (odds ratio = 20.8; 95% confidence interval, 2.82-153; P = 0.003). This study is the first to indicate that non-dipping PR is significantly associated with chronic microanatomical changes in the kidneys of patients with CKD.

An exploration on retro-construction of plasma drug concentration-time curves from corresponding urine excretion data and single-point plasma concentrations using a simplified and idealized method.

Despite the availability of various tools of modeling and simulation, clinical pediatric pharmacokinetic (PK) studies remain far less efficient than those on adults due to ethical constraints. One of the optimal solutions is to substitute urine to blood sampling based on explicit mathematic relationships between them. However, this idea is limited by three main knowledge gaps associated with urine data, i.e., complicated excretion equations with excessive parameters, insufficient frequency that is hard to fit, and the mere expression of amounts with no in vivo distribution volume information involved. To overcome these obstacles, we sacrificed the precision from mechanistic PK models with complex excretion equations to expediency of compartmental model in which a constant ke is used to cover all the internal parameters. And the total cumulative amounts of urinary drug excretion were estimated and introduced to the excretion equation so that urine data were likely to be fitted using a semi-log-terminal linear regression method. In addition, urinary excretion clearance (CLr) could be calculated by single point plasma data to anchor the plasma concentration-time (C-t) curve based on the assumption that CLr was kept constant throughout the PK process. After sensitivity analysis of two subjective judgements (the selection of the compartmental model and the selection of plasma time point to calculate CLr), the performance of the optimized models was assessed using desloratadine or busulfan as model drugs in a variety of PK scenarios, from i.v. bolus/infusion to p.o. administration, from a single dose to multiple doses, and from rats to children. The fitting plasma drug concentrations of the optimal model were close to the observed value. Meanwhile, the drawbacks inherent to the simplified and idealized modeling strategy were fully identified. The method proposed by this tentative proof-of-principle study was able to deliver acceptable plasma exposure curves and shed light on the future refinements.

Exposure to organophosphorus compounds of Japanese children and the indoor air quality in their residences

Several organophosphorus compounds such as organophosphate pesticides (OPPs) and trialkylphosphates (TAPs) are suspected to inhibit cholinesterase activities, to affect endocrine systems or to possibly be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially in children, we measured the household exposure to OPPs and TAPs by Japanese children via all exposure pathways and the contribution of indoor air quality. First-morning void urine was collected from subjects aged 6 to 15 years (n = 132), and airborne organophosphorus compounds were sampled in the subject's bedroom for 24 h. Airborne levels of nine OPPs and three TAPs and their urinary metabolites were determined.No significant correlations were detected for any compounds between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The estimated daily intakes were as follows (median, μg/kg b.w./d): chlorpyrifos, 0.042; diazinon, 0.067; tri-n-butylphosphate, 0.094. The 95th percentiles of the intakes for fenthion, fenitrothion and the above three compounds did not exceed their reference limit values, although one subject had a daily intake of tri-n-butylphosphate that was about twice its reference limit value. The concentration levels of the urinary metabolite of tri-n-butylphosphate in our subjects tended to be higher than those for children in many other countries. The fractions of the amounts absorbed by inhalation to the amounts absorbed via all of the exposure pathways was only 2.3 % (median) for tri-n-butylphosphate.Inhalation did not seem to contribute very much as an absorption pathway of the organophosphorus compounds in these Japanese children while they were at home. The exposure amounts of OPPs were not suggested to be high enough to adversely affect the health of these children at present on the basis of their daily intakes compared to their reference limit values.

Chemical Analysis Study of Kidney Stones in Iraqi Community

The urinary tract system is one of the most important system in human body to control many functions and get any wastes out of body, many diseases may affect this function and prevents it to work effectively. One of this disease is nephrolithiasis at which salt forming stone are settled in renal system affecting its work. The qualitative biochemical analysis of compositions of each stone was done for carbonate, calcium, magnesium, phosphate, oxalate, uric acid, and cysteine, using stone powder derived from the stones. These results found that Calcium oxalate stones were more likely to be detected in patients with upper urinary tract stones (p &lt; 0.001). It was observed in 5.3% of cases which was apparently lower than previous data in nationwide urinary stone composition analysis. the most common type of stone was calcium oxalate (84.1%); others were calcium oxalate phosphate (8.0%), ammonia (3.4%), calcium uric acid (2.3%) and calcium carbonate (1.1%). A defect in ammonium excretion would account for the undue urinary acidity; then, increased urine acidity promotes uric acid super saturation. The amount of urinary oxalate excretion is a significant factor in the development of CaOx stones. Aim of study to know how to prevent stone recurrence and formation requiring better knowing mechanisms contributed in this stone formation.

PHYSICAL THERAPY OF PATIENTS WITH POST-TRAUMATIC GONARTHROSIS WITH IMBALANCE OF OSTEO-ASSOCIATED MACRONUTRIENTS

According to modern concepts, bone remodeling disorders that are directly dependent on the imbalanceof osteo-associated trace elements play a key role in the pathogenesis of OA. Therefore, the purpose of ourstudy is to develop the program of physical rehabilitation of patients with post-traumatic gonarthrosisand to investigate its effect on the composition of osteoassociated macronutrients.To determine the metabolic function of bone tissue there were the results of the study of mineralhomeostasis by the level in the peripheral blood of phosphorus and magnesium, total calcium and itsionized form, as well as the amount of urinary calcium excretion. The processes of bone formation wereevaluated by the content of bone isoenzyme of alkaline phosphatase, bone resorption was evaluated bythe level of tartrate-resistant acid phosphatase. 42 patients with post-traumatic osteoarthritis of the kneejoints of I–II stages according to Kellgren-Lowrence were observed.The complex of physical therapy included the educational program, medical gymnastics and massage.The theoretical part of the program included 6 topics covering the main issues related to the risk factorsand prognosis for the disease, the main mechanisms of its progression, as well as the basics of differentphysical therapy use. The practical part of the program was carried out in a small-group way and includedthe gradual application of static, dynamic, active and proprioceptive neuromuscular stretching usingthe exercises with elastic bands and metered loading. As for the massage technology a combinationof segmental massage with Swedish technique was used in the program. The total duration of the complexprogram was 9 months, after which patients were advised to perform independent classes. The applicationof the developed program of physical rehabilitation had a positive effect on the processes of boneremodeling, and allowed to reduce the number of exacerbations during the year.

Preliminary bronchodilator dose effect on aerosol-delivery through different nebulizers in noninvasively ventilated COPD patients

Objectives: This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. Method: COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose. Results: The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens(p < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery (p < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN (p < 0.001). Conclusion: Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.

The Role of Monocyte to High-Density Lipoprotein Cholesterol Ratio in Predicting the Severity of Proteinuria and Renal Dysfunction in Primary Nephrotic Syndrome.

Introduction: Monocyte to high-density lipoprotein (HDL) cholesterol ratio (MHR) has emerged as a novel marker of endothelial injury, inflammation, and oxidative stress. This study aimed to investigate the effect of MHR on primary nephrotic syndrome (NS) and its relationship with the severity of proteinuria.Methods: This study enrolled 161 patients newly diagnosed with primary NS and 100 healthy individuals. Demographic characteristics of the patients, primary NS diagnosis, basal laboratory parameters, the amount of 24-hour urinary protein excretion, and MHR were recorded. The groups were compared regarding these parameters.Results: MHR was significantly higher in patients with primary NS compared with the healthy group (12.89 ± 4.86 and 9.71 ± 2.30, respectively; p < 0.001). There was no difference between the groups in terms of age and sex. The amount of protein in the 24-hour urine in patients with a diagnosis of primary NS was 6.91 ± 3.73 g/day. The correlation analysis showed a positive correlation between MHR and the amount of proteinuria (r = 0.519, p < 0.001) and creatinine level (r = 0.167, p = 0.034). The multivariate regression analysis found that the severity of proteinuria was independently correlated to MHR (p < 0.001). According to the receiver operating characteristic curve analysis, the optimal cut-off level for MHR in NS was 10.08 (area under the curve of 0.704, sensitivity of 68%, and a specificity of 62%).Conclusion: Our study is the first to compare the severity of proteinuria and renal functions with MHR in patients with primary NS. We believe that MHR can be used as a biomarker to determine inflammation, endothelial injury, and the level of oxidative stress, and may be useful to predict prognosis in patients with primary NS.

A STUDY OF CORRELATION OF SPOT URINE PROTEIN-CREATININE RATIO WITH 24HOUR URINARY PROTEIN IN TYPE 2 DIABETES MELLITUS PATIENTS AT A TERTIARY CARE HOSPITAL

Background:Diabetic nephropathy is the major cause for chronic renal failure (CRF) and proteinuria is an independent risk factor for end stage renal disease. Hence, early identification and quantification of proteinuria is of prime importance in the diagnosis and management. Method: The present study is a prospective observational study conducted amongst 50 diabetic subjects in Medicine department &amp; IKDRC,Civil Hospital Ahmedabad.The study carried out during the period between July 2017 to October 2019. All patients were treated as per standard treatment protocol. 24-hour urine protein and random urine protein to creatinine ratio (P:C) was determined. Result: Total 50(24 male &amp;26 female) patients were studied. A strong correlation was found between 24 hours urine protein and protein- Creatinine ratio, especially in patient with eGFR &gt;30 (CKD stage I to III) with coefficient of correlation of 0.973.However correlation weaken as the GFR worsens and is weakest in patients with stage 5 CKD Conclusion: The random urine Protein:Creatinine ratio predicts the amount of 24-hour urinary protein excretion with high accuracy.Hence it can be used as a faster substitute test for 24-hour urinary protein estimation.

The Effect of Oxalobacter formigenes Colonization in Patients with Calcium Oxalate Renal Stones in Comparison with Healthy People in Qom: A Case-Control Study

Background: Urinary stones are a major problem world, and their incidence has increased significantly in recent years. Objectives: This study aimed to develop a simple and rapid molecular method based on PCR and qPCR assays to detect Oxalobacter formigenes (which causes oxalate degradation in intestines) in fecal samples of healthy volunteers and patients with calcium oxalate nephrolithiasis, and determine the amount of urinary oxalate in the two groups. Methods: This study was performed on urine and fecal samples of 73 patients with kidney stones and 52 healthy individuals. After DNA extraction, PCR and qPCR assays were performed on two gene regions of O. formigenes, OXC, and FRC. Also, urine oxalate was measured in the study population using biochemical methods. Results: We found that the presence of O. formigenes could reduce the risk of kidney stones and calcium oxalate stones. In fact, both FRC and OXC genes were involved in the diagnosis of O. formigenes; however, the results based on the FRC gene showed higher efficiency. In addition, the presence or absence of stones did not affect the amount of urinary excretion of oxalate, rather it is affected by diet. Conclusions: Molecular identification of O. formigenes by PCR and qPCR assays allows rapid, specific, and reproducible detection in fecal samples, which also allows immediate processing of these samples in clinical conditions.

Estimating household exposure to moth repellents p-dichlorobenzene and naphthalene and the relative contribution of inhalation pathway in a sample of Japanese children

p-Dichlorobenzene (DCB) and naphthalene (NP) used as moth repellents in indoor environments are suspected to be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially children, we need to know their amounts absorbed by the body and the relationships between their amounts and air quality in residences. At present, little is known worldwide about them.This study examined the daily intakes of DCB and NP by Japanese children via all exposure pathways and the contribution of indoor air quality to the intakes. First-morning void urine samples from the subjects aged 6 to 15 years and air samples in their bedrooms were collected. Airborne NP and DCB and their urinary metabolites were measured.Significant correlations were detected between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The absorption amounts of DCB and NP by inhalation of the children while at home were calculated to be 26 and 2.0 ng/kg b.w./h, respectively, as median values. The daily intake was estimated to be 2.4 and 0.90 μg/kg b.w./d (median), respectively. The fractions (median) of inhalation absorption amounts to overall absorption amounts for DCB and NP were 30% and 5%, respectively. In children living in residences where the indoor air concentrations of these compounds were more than half the level of each guideline value for indoor air quality, the main exposure route for their absorption was considered to be inhalation while at home. The indoor concentrations of DCB exceeded the lifetime excess cancer risk level of 10−4 in 22% of the residences and 10−3 in 9% of them. Our findings indicate the need to further reduce airborne concentrations of DCB in Japanese residences to prevent its adverse effects on the health of Japanese children.

Gadolinium retention within multiple rat organs after intra-articular administration of gadolinium-based contrast agents

ObjectiveTo characterize the extent of retention and biodistribution of gadolinium (Gd) following intra-articular (IA) injection of linear and macrocyclic gadolinium-based contrast agents (GBCAs) into the knee joint of a rat model.Materials and methodsFifteen Wistar rats were divided into five groups and underwent fluoroscopically-guided injections of both knee joints of (1) clinical 1:200 dilution (low dose, LD) gadodiamide (linear GBCA), (2) LD gadobutrol (macrocyclic GBCA), (3) undiluted (high dose, HD) gadodiamide, (4) HD gadobutrol, and (5) saline. Gd concentrations were quantified by inductively coupled plasma mass spectrometry in (1) blood and urine samples obtained over a 72 h period and (2) knee joint tissues, brain, kidney, and bone marrow at 3 days post-injection.ResultsBoth HD and LD gadodiamide and gadobutrol were rapidly absorbed from the joint with peak serum and urine concentration at 1 h post-injection, with relatively faster clearance of gadobutrol. All GBCA-exposed groups had detectable levels of Gd in the joint tissues, bone marrow, and/or kidneys (median tissue gadolinium range: 0.1–71 μg Gd/g tissue), with higher amounts observed with gadodiamide versus gadobutrol. Retention within brain tissues was only detected following HD gadodiamide administration but not LD gadodiamide nor HD or LD gadobutrol.ConclusionThere was rapid systemic absorption, redistribution, and widespread multi-organ retention of Gd following IA injection of both linear and macrocyclic GBCAs, despite substantial amounts of urinary excretion. Higher concentrations of Gd were observed with administration of gadodiamide compared to gadobutrol in most tissues and biofluids.

Is Water-Only Fasting Safe?

BackgroundWater-only fasting (WF) is a practice used to improve and maintain health.ObjectiveThe aim of the study was to show whether WF performed for 8 days may be a threat to the health and/or life of people undergoing this practice.MethodsTwelve middle-aged men participated in the study. During the 8-day WF, the subjects ate no food except for drinking mineral water. Before and after WF, all subjects had a series of tests performed, beginning with the level of perceived stress and somatic measurements. The concentrations of creatinine, sodium (Na+), potassium (K+), total calcium (Ca), magnesium (Mg++), urea (U), uric acid (UA) and total protein were determined in this urine and in the serum. For these substances, the values ​​of clearance, renal filtration and fractional excretion were calculated. The osmotic clearance and free water clearance as well as the amount of daily urinary excretion of creatinine, Na+, K+, Ca, Mg++, U and UA were also calculated. Moreover, the concentration of glucose in the serum and the concentration of β-hydroxybutyrate in the plasma were determined. In urine, specific gravity, pH and osmolality were also measured.ResultsAfter 8 days of WF, the study showed a significant reduction in the level of perceived stress, weight loss, changes in body composition, dehydration, increased ketogenesis, hyperuricemia, decreased serum glucose concentration, and hyponatremia. These changes were accompanied by Na+, K+ and protein sparing, decreased serum Ca and Mg++ concentrations, and reduced daily volume of more acidic urine with elevated specific gravity.ConclusionsAfter 8 days of WF, all subjects were found to remain safe and feel the sense of well-being. However, the appearance of the above-mentioned adverse metabolic effects, despite partially effective renal compensations, suggests that the further continuation of fasting intervention by the subjects would be detrimental to their body.

Correlation Between Serum Creatinine &amp; Urine Albumin in Diabetic Nephropathy Patients

Diabetic nephropathy has some distinct stages and each of the stages are individually defined according to different amount of albumin excreted through urine. Serum creatinine is a very common tool of renal assessment in diabetic nephropathy. This study aims at observation of existing correlation between serum creatinine and urine albumin in diabetic nephropathy patients. This cross sectional observational study has been conducted on 50 diabetic patients admitted to medicine department of Dhaka Medical College Hospital. Patients were included in this study after fulfilling inclusion and exclusion criteria in a period January 2018 to June 2018. After selection, data were collected by structured questionnaire. Then 24 hour urinary total protein, urine for microalbumin, complete blood count, fasting blood sugar, two hours postprandial blood sugar, HbA1C, serum creatinine report were collected and analyzed it with the help of SPSS 16.0 MS excel. Among total 50 patients, 34 patients were diagnosed on the basis of microalbuminuria and the rest were found to have raised urinary total protein. The male patients were 54 percent of the total population. Most of the patients were in between the age of 57 to 67 years. The r value is insignificant in two graphs where serum creatinine was compared with urine microalbumin and serum creatinine respectively, which suggests absence of linear or any other correlation between these two components. The estimated Glomerular Filtration Rate (eGFR) was calculated by MDRD equation individually. Staging was done on the base of eGFR. Only 41.37% of the patients with microalbuminuria, showed eGFR consistent with its staging while only 31.5% of the patients with proteinuria showed respective expected eGFR. And the difference between the mean serum creatinine in two groups was insignificant. This study has shown that, the serum creatinine has no linear correlation with urinary albumin in diabetic nephropathy patients. So, commonly used serum creatinine based formula to calculate the estimated GFR cannot reflect the amount of urinary protein excretion all the time. So it can misinterpret the staging of the disease which can delay the appropriate treatment of the patient.&#x0D; J Dhaka Medical College, Vol. 27, No.2, October, 2018, Page 141-147

The effect for hyperuricemia inpatient of uric acid overproduction type or in combination with topiroxostat on the pharmacokinetics, pharmacodynamics and safety of dotinurad, a selective urate reabsorption inhibitor

BackgroundDotinurad, a novel selective urate reabsorption inhibitor (SURI), increases urinary uric acid excretion. The aim of this study is to examine the pharmacokinetics, pharmacodynamics, and safety of dotinurad according to the type of hyperuricemia, with or without concomitant use of xanthine oxidase inhibitor, in uric acid “overproduction type” patients.MethodsThis open-label clinical pharmacology study was conducted in a hospital. Dotinurad 1 mg was administered for 7 days to hyperuricemic patients with uric acid “overproduction type” (overproduction group, n = 6; and combination group, n = 6) and uric acid “underexcretion type” (underexcretion group, n = 6). In the combination group, topiroxostat 80 mg was used concomitantly.ResultsNo significant differences were observed in pharmacokinetics and safety between overproduction group and underexcretion group, and the percent change in serum uric acid level and the amount of urinary uric acid excretion after administration were comparable. In “overproduction type” patients of combination group, the percent change in serum uric acid level significantly increased and the amount of urinary uric acid excretion significantly decreased compared to those of overproduction group. No clinically meaningful differences were observed in safety between the overproduction group and the combination group.ConclusionIn inpatients, differences in hyperuricemic type did not significantly influence the pharmacokinetics, pharmacodynamics, and safety of dotinurad. Moreover, in “overproduction type”, the coadministration of dotinurad and topiroxostat had an add-on serum uric acid lowering effect and suppressed urinary uric acid excretion.Trial registrationClinicalTrials.gov Identifier: NCT02837198.

Quantitative biokinetics over a 28\u2009day period of freshly generated, pristine, 20 nm titanium dioxide nanoparticle aerosols in healthy adult rats after a single two-hour inhalation exposure

BackgroundIndustrially produced quantities of TiO2 nanoparticles are steadily rising, leading to an increasing risk of inhalation exposure for both professionals and consumers. Particle inhalation can result in inflammatory and allergic responses, and there are concerns about other negative health effects from either acute or chronic low-dose exposure.ResultsTo study the fate of inhaled TiO2-NP, adult rats were exposed to 2-h intra-tracheal inhalations of 48V-radiolabeled, 20 nm TiO2-NP aerosols (deposited NP-mass 1.4 ± 0.5 μg). At five time points (1 h, 4 h, 24 h, 7d, 28d) post-exposure, a complete balance of the [48V]TiO2-NP fate was quantified in organs, tissues, carcass, lavage and body fluids, including excretions.After fast mucociliary airway clearance (fractional range 0.16–0.31), long-term macrophage-mediated clearance (LT-MC) from the alveolar region is 2.6-fold higher after 28d (integral fraction 0.40 ± 0.04) than translocation across the air-blood-barrier (integral fraction 0.15 ± 0.01). A high NP fraction remains in the alveoli (0.44 ± 0.05 after 28d), half of these on the alveolar epithelium and half in interstitial spaces. There is clearance from both retention sites at fractional rates (0.02–0.03 d− 1) by LT-MC. Prior to LT-MC, [48V]TiO2-NP are re-entrained to the epithelium as reported earlier for 20 nm inhaled gold-NP (AuNP) and iridium-NP (IrNP).ConclusionComparing the 28-day biokinetics patterns of three different inhaled NP materials TiO2-NP, AuNP and IrNP, the long-term kinetics of interstitial relocation and subsequent re-entrainment onto the lung-epithelium is similar for AuNP and Ir-NP but slower than for TiO2-NP. We discuss mechanisms and pathways of NP relocation and re-entrainment versus translocation. Additionally, after 28 days the integral translocated fractions of TiO2-NP and IrNP across the air-blood-barrier (ABB) are similar and become 0.15 while the translocated AuNP fraction is only 0.04. While NP dissolution proved negligible, translocated TiO2-NP and IrNP are predominantly excreted in urine (~ 0.1) while the urinary AuNP excretion amounts to a fraction of only 0.01. Urinary AuNP excretion is below 0.0001 during the first week but rises tenfold thereafter suggesting delayed disagglomeration. Of note, all three NP dissolve minimally, since no ionic radio-label release was detectable. These biokinetics data of inhaled, same-sized NP suggest significant time-dependent differences of the ABB translocation and subsequent fate in the organism.

Distribution of pathogenic bacteria in women with cystitis in community and treatment strategies

Objective To investigate the bacterial distribution characteristics of female cystitis patients in the community and evaluate the effect of using different antimicrobial agents. Methods Female patients with cystitis from January 2015 to January 2017 in our hospital were selected to receive clean midstream bacteriological culture before treatment to analyze the distribution characteristics of pathogens, and were randomly divided into fosfomycin treatment group and routine treatment. In the fosfomycin-treated group, the fosfomycin tromethamine was scattered, and in the conventional treatment group, according to the conventional anti-infective drugs, the curative effect, the detection index, and the concentration of RhoA/Rho kinase were compared between the two groups after the third and seventh days after taking the drugs. Results The urine cultures of 157 patients were all positive. A total of 144 gram-negative bacteria (91.7%) were isolated with Escherichia coli and 13 were gram-positive (8.3%). After 3 days of treatment, the efficacy of the fosfomycin-treated group was better than that of the conventional treatment group (P 0.05), and the concentration of RhoA/Rho kinase decreased after treatment (P<0.05). In addition to the total amount of urinary excretion in the fosfomycin-treated group, other testing indicators and RhoA/Rho kinase concentrations were lower than those in the conventional treatment group (P<0.05). The Chaol, Simpson index and the relative abundance of all types of bacteria of the fosfomycin-treated group was significantly lower than that of the conventional treatment group (P<0.05). Conclusions The main pathogen of female cystitis in the community is Gram-negative bacteria mainly composed of Escherichia coli, which can be used as the first-line drug for the treatment of female cystitis. Key words: Cystitis; Femininity; Opportunistic Infections