Higher Excretion Research Articles

Hoven’s carp Leptobarbus hoevenii strategized metabolism needs to cope with changing environment

Current water warming and freshwater acidification undoubtedly affect the life of aquatic animals especially ammonotelic teleost by altering their physiological responses. The effect of temperature (28 °C vs 32 °C) and pH (7 vs. 5) on the metabolic compromising strategies of Hoven's carp (Leptobarbus hoevenii) was investigated in this study. Fishes were conditioned to (i) 28 °C + pH 7 (N28°C); (ii) 32 °C + pH 7 (N32°C); (iii) 28 °C + pH 5 (L28°C) and (iv) 32 °C + pH 5 (L32°C) for 20 days followed by osmorespiration assay. Results showed that feeding performance of Hoven's carp was significantly depressed when exposed to low pH conditions (L28°C and L32°C). However, by exposed Hoven's carp to L32°C induced high metabolic oxygen intake and ammonia excretion to about 2x-folds higher compared to the control group. As for energy mobilization, Hoven's carp mobilized liver and muscle protein under L28°C condition. Whereas under high temperature in both pH, Hoven's carp had the tendency to reserve energy in both of liver and muscle. The findings of this study revealed that Hoven's carp is sensitive to lower water pH and high temperature, thereby they remodeled their physiological needs to cope with the environmental changes condition.

The profile of cholesterol metabolism does not interfere with the cholesterol-lowering efficacy of phytostanol esters

Increasing evidence suggests that high cholesterol absorption efficiency enhances the risk of atherosclerotic cardiovascular diseases. It is not known whether inhibiting cholesterol absorption has different metabolic effects in high- vs. low cholesterol absorbers. We evaluated the effects of phytostanol esters on serum lipids and cholesterol metabolism in a post hoc study of three randomized, double-blind, controlled trials. The participants were classified into low (n=20) and high (n=21) cholesterol absorbers by median cholesterol absorption efficiency based on the plasma cholesterol absorption marker cholestanol at baseline. The participants consumed mayonnaise or margarine without or with phytostanol esters for six to nine weeks without other changes in the diet or lifestyle. Serum cholesterol, cholestanol, lathosterol, and faecal neutral sterols and bile acids were analysed by gas-liquid chromatography. According to power calculations, the size of the study population (n=41) was appropriate. During the control period, cholesterol synthesis, and faecal neutral sterols and bile acids were lower in high- vs. low absorbers (p<0.05 for all). Phytostanol esters reduced low-density lipoprotein cholesterol by 10-13% in both groups, and directly measured cholesterol absorption efficiency by 41±7% in low- and 47±5% in high absorbers (p<0.001 for all) without side effects. Cholesterol synthesis and faecal neutral sterols (p<0.01) increased in both groups, more markedly in the high vs. low absorbers (p<0.01). Low cholesterol absorption combined with high faecal neutral sterol excretion are components of reverse cholesterol transport. Thus, high- vs. low absorbers had a more disadvantageous metabolic profile at baseline. In both groups, phytostanol esters induced favourable changes in serum, lipoprotein, and metabolic variables known to help in prevention of the development of atherosclerotic cardiovascular diseases.

Association between sodium-to-potassium ratio in spot urine and hospitalization due to heart failure in high-risk Japanese patients

BackgroundIn Japanese cardiovascular (CV) high-risk patients, the ESPRIT (Evaluation of Sodium Intake for the Prediction of Cardiovascular Events in Japanese High-risk Patients) study showed that high sodium excretion (≥4.0 g/day) was associated with a composite CV events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and CV deaths. In this context, the sodium-to-creatinine (Na/Cr) ratio in spot urine was found to be significantly associated with HF hospitalizations. Since a stable potassium balance plays a particularly relevant role for CV patients, this post-hoc study was designed to investigate the extent to which consideration of the sodium-to-potassium (Na/K) ratio represents a better predictor of HF hospitalizations in the ESPRIT study population. MethodsThis is a post-hoc analysis of a previously reported ESPRIT study (n = 520, 60 HF hospitalizations). ResultsReceiver operating curve analysis yielded optimal Na/K ratio cut-off value of 2.9 for detecting HF hospitalization. Kaplan–Meier curve showed that high Na/K ratio in spot urine was associated with increased HF hospitalization (p < 0.001). Cox proportional hazards model analysis revealed that high Na/K ratio was associated with HF hospitalization with a hazard ratio of 2.97 (confidence interval: 1.67–5.61). An association between high Na/K ratio and HF hospitalization remained after adjustments for Na/Cr ratio in spot urine or the use of diuretics. ConclusionThe Na/K ratio in spot urine is associated with HF hospitalization in high-risk Japanese patients.

In Silico Screening of Leguminosae Phytochemicals as Potential Inhibitors of Lung Cancer: A Structure-Based Multi-Targeted Molecular Docking Analysis

About half of the chemotherapeutic drugs are naturally occurring anticancer compounds which are available in the market to date. In silico virtual screening for new anti-cancer drug discovery is a cost-effective method as compared to traditional drug synthesis. From Leguminosae family 144 phytochemicals which were screened from the Dictionary of Natural Products (DNP) undergo molecular docking in comparison to approved drugs Gemcitabine, osimertinib, and Nintedanib against targeted proteins EGFR, BRAF, and KRAS. Only five phytochemicals are 2-Pyrrolecarboxylate, O-(3, 5-Dihydroxy-4-methoxy benzoyl), ?-Aldotripiperideine, O8-(2-Pyrrolecarbonyl), and Benzoyl with high docking scores were selected for further studies based on ADMET lab. In this article, phytochemicals that can inhibit protein growth causing lung cancer were screened and selected by using molecular docking or ADME analysis. In silico ADME studies of these selected phytochemicals suggest that 2-Pyrrolecarboxylate, O-(3,5-Dihydroxy-4-methoxy benzoyl), and O8-(2-Pyrrolecarbonyl) are completely safe, non-toxic, non-carcinogenic, non GERG blocker, do not cause liver injury and have high excretion rate and can be taken for further in vivo and in vitro studies to discover new chemotherapy against lung cancer.

Environmental fluoride exposure and implications on potential pediatric kidney health risks: an approach with urinary biomarkers.

Environmental fluoride exposure at elevated levels is potentially linked to kidney injury, and may contribute to chronic kidney disease of uncertain etiology (CKDu) as a risk factor. However, this link remains unclear, and examining the risk of kidney damage from early life fluoride exposure may provide important insights. Hence, this study aimed to investigate associations of fluoride exposure with pediatric kidney health in CKDu impacted and unimpacted communities in Sri Lanka. Considering the geographical variations in environmental fluoride, climate, and prevalence of CKDu, four study groups were established within selected education zones in CKDu-endemic dry zone regions (D-En), and CKDu-nonendemic regions within the dry (D-NE), wet (W-NE), and intermediate (I-NE) climatic zones. The study population included 922 school students (11-18 years of age). Participants in each group were divided into four subgroups based on quartiles of respective urinary fluoride (UF) distribution for comparison of urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin-creatinine ratio (ACR). UF levels in participants particularly in CKDu endemic dry zone regions were significantly high compared to the other regions. Significantly high median urinary NGAL (in D-NE) and ACR (in D-EN, and W-NE) levels were observed in subgroups of higher UF quartiles. Albuminuria was not particularly identified in subjects with high UF excretion. Urinary KIM-1 showed no significant variation across the UF quartile subgroups. Linear regression identified weak associations of UF with kidney injury biomarkers. Fluoride exposure is particularly high in CKDu-endemic dry zone communities. As implied by kidney injury biomarkers, a strong link between fluoride exposure and pediatric kidney health was not evident at the observed exposure levels in the study regions.

Hyponatremia: A Rare Complication of Gitelmans's Syndrome - Literature Review and Clinical Case

Abstract Gitelman's syndrome (GS) is a variant of classical Bartter's syndrome (BS) in adults characterized by hypokalemic metabolic alkalosis, hypocalciuria (daily excretion &lt;2.0 mg/kg body weight), hypomagnesaemia (&lt;1.5 mg/dl), together with a normal to low blood pressure. In 1996, Simon et al. reported complete linkage between the syndrome and the thiazide-sensitive sodium chloride coporter (TSC) on chromosome 16q13 (Human Gene Mapping Workshop-approved symbol: SLCA3). Other metabolic features of GS include normonatremia, hyperuricemia, normocalcemia, increased plasma renin and aldosterone/potassium ratio, and inappropriately high renal potassium, magnesium, and chloride excretion. In this paper, we describe two affected patients who developed severe hyponatremia and hypouricemia. To the best of our knowledge, this complication has not been described previously.

Plasma disposition and faecal excretion of eprinomectin following subcutaneous administration in Saanen and Alpine goats

Eprinomectin is extensively used in veterinary medicine, particularly in the treatment of internal and external parasites in livestock, including goats. The pharmacokinetic behavior of eprinomectin in plasma and faeces was studied after a single subcutaneous administration in two different goat breeds at a dose of 0.2 mg/kg body weight. The study was conducted on one-year-old female Saanen (n = 8) and Alpine (n = 8) goats in a parallel design. There were no significant differences between Saanen and Alpine goats on the peak plasma concentration (Cmax, 28.59 ± 7.46 ng/mL vs. 37.69 ± 14.89 ng/mL), area under the curve (AUC0-∞, 93.08 ± 11.66 ng.d/mL vs. 116.98 ± 48.36 ng.d/mL), area under the first moment curve (AUMC0-∞, 311.05 ± 67.23 ng.d2/mL vs. 348.25 ± 202.64 ng.d2/mL) and mean residence time (MRT, 3.24 ± 0.77 d vs. 2.74 ± 0.64 d) values. The plasma terminal half-life and the time to reach peak plasma concentration were significantly higher in Saanen goats (T1/2λz, 2.18 ± 0.43 d; Tmax, 1.21 ± 0.25 d) than in Alpine goats (T1/2λz, 1.66 ± 0.41 d; Tmax, 0.79 ± 0.25 d). The results revealed that the plasma concentration of eprinomectin did not differ depending on the breed in Saanen and Alpine goats. However, it was determined that the eprinomectin clearance from the body may vary depending on the breed in goats. The faecal eprinomectin concentration of Saanen and Alpine goats was 90 and 80 times higher than the plasma eprinomectin concentration, respectively. Although high faecal excretion of eprinomectin confers a high efficacy advantage against parasites in the gastrointestinal tract, it may pose an ecotoxicological risk to manure fauna and aquatic organisms with high susceptibility to this compound.

Pathomorphological Findings and Infectious Diseases in Selected European Brown Hare (Lepus europaeus Pallas, 1778) Populations from Schleswig-Holstein, Germany.

In the northernmost German federal state Schleswig-Holstein, populations of European brown hares (Lepus europaeus Pallas, 1778) show diverse densities and varying courses over the years. To examine differences in pathomorphological findings and infectious diseases as possible reasons for varying population dynamics, we assessed 155 hunted hares from three locations in Schleswig-Holstein from 2016 to 2020. We investigated the association of location, year, age, and sex of animals to certain pathomorphological findings and infectious diseases. Frequent pathomorphological findings were intestinal parasites (63.9%), hepatitis (55.5%), nephritis (31.0%), steatitis (23.2%), enteritis (13.5%), and pneumonia (5.2%). Body condition differed significantly between locations, and the prevalence of pneumonia was significantly higher in females. Enteritis was not detected in 2019, when much more juveniles were sampled. Hepatitis and nephritis occurred significantly more often in 2016 and among adults. Additionally, more adults showed hepatitis with concurrent serotitre for European brown hare syndrome virus (EBHSV), while intestinal parasitosis as well as high excretion rates of coccidia were more common in juveniles. Sampled animals showed high infection rates with Eimeria spp. (96.1%), Trichostrongylus spp. (52.0%), Graphidium strigosum (41.2%), and a high seroprevalence (90.9%) for EBHSV, without severe symptoms. This study revealed a low prevalence of infectious pathogens, but a high prevalence of chronic inflammations of unknown origin in the tested brown hare populations. Overall, our results indicate a rather minor importance of infectious diseases for observed population dynamics of analysed hare populations in Schleswig-Holstein.

Preparation, Radiolabeling with 68Ga/177Lu and Preclinical Evaluation of Novel Angiotensin Peptide Analog: A New Class of Peptides for Breast Cancer Targeting.

Angiotensin II (AngII) is known to play a significant part in the development of breast cancer by triggering cell propagation of breast cancer, tumor angiogenesis, and regulating tumor invasion and cell migration. AngII arbitrates its action via two G-protein-coupled receptors, AngII type 1 receptor (AT1) and AngII type 2 receptor (AT2). Overexpression of the AT1 receptor in breast cancer cells seems to promote tumor growth and angiogenesis, thus targeting the AT1 receptor using AngII peptide would facilitate the detection of breast carcinoma. We developed an AngII peptide intending to assess whether the peptide of the renin-angiotensin system holds the ability to target AT1 receptor-overexpressing breast cancer in vivo. DOTA-coupled AngII peptide was synthesized by conventional solid-phase peptide synthesis according to Fmoc/HATU chemistry. 68Ga/177Lu labeled AngII peptide was evaluated for its binding with TNBC MDA-MB-231 and ER+ MCF7 cell lines. Pharmacokinetics was studied in healthy balb/c mice and in vivo tumor targeting in nude mice with MDA-MB-231 tumors xenografts. DOTA-AngII peptide was labeled efficiently with 68Ga/177Lu with high labeling efficiency (≥90%). The stability of the radiopeptide in human plasma was found to be high. The AngII peptide analog showed nanomolar (<40 nM) AT1 receptor-specific binding affinity. The radioactivity internalized into MDA-MBA-231 and MCF7 cells were 14.97% and 11.75%, respectively. In vivo, biodistribution in balb/c mice exhibited efficient clearance of 68Ga/177Lu-DOTA-AngII peptide from the blood and elimination predominantly by the renal system due to its hydrophilic nature. A low amount of radioactivity was seen in the major organs including lungs, liver, stomach, spleen, and intestines (<3% ID/g) except the kidneys. A high renal-urinary excretion was observed for the radiotracer. In the TNBC MDA-MB-231 xenografts model, radiolabeled AngII peptide exhibited specific and effective AT1-based targeting in vivo. A rapid and efficient tumor targeting (2.18% ID/g at 45 min p.i.) together with fast renal excretion (~67% ID) highlights the tumor-targeting potential of the radiotracer. The AT1 receptor specificity of the radiotracer was validated by blocking assays. Furthermore, PET imaging provided sufficient visualization of MDA-MB-231 tumors in nude mice. Our findings suggest that 68Ga/177Lu-DOTA-AngII peptide can be useful for the theranostic application of breast carcinomas. This study suggests the potential of this innovative class of peptides for rapid and efficient targeting of tumors and warrants further evaluation.

Interleukin-6 and Epidermal Growth Factor as non-invasive biomarkers of progression in chronic glomerulonephritis.

Several cytokines and chemokines are involved in the pathogenesis and progressive injury of renal tissues in patients with primary chronic glomerulonephritis (CGN). The objective of this study was to determine whether the urinary excretion of interleukin-6 (IL-6), transforming growth factor β1 (TGFβ1), monocytes chemoattractant protein (MCP-1), soluble tumor necrosis factor receptor 1 (sTNFR1) and epidermal growth factor (EGF) in patients with newly recognized CGN can serve as prognostic biomarkers in patients with newly recognized CGN and whether they can be effective in predicting a progressive reduction of renal function in prospective observation. The study included 150 Caucasian patients. UIL-6, UTGFβ1, UMCP-1 and UsTNFR1 and UEGF were measured using ELISA methods (Quantikine R&D System). UIL-6, UTGFβ1, UMCP-1 and UsTNFR1 were significantly higher, yet UEGF excretion was significantly lower in nephrotic patients, in patients with estimated glomerular filtration rate (eGFR) < 60/min/1,73m2 at presentation, as well as in the progressor (PG) subgroup. In a multivariate regression analysis basal eGFR correlated with UsTNFR1, UIL-6 and UEGF excretion, although in the follow-up, ΔeGFR (delta estimated glomerular filtration rate) significantly correlated only with UEGF excretion. A logistic regression analysis showed that the most significant independent risk factors for the deterioration of renal function with time are initial high (>11.8 pg/mgCr) UIL-6 excretion, initial low (<15.5 ng/mgCr) urinary UEGF excretion and male gender. In patients with newly diagnosed CGN, UIL-6 and UEGF can serve as prognostic biomarkers for the progression of the disease.

Iodine status of school-aged children in the changing context of universal salt iodization program during 1997–2018 in Chongqing, China

ObjectiveTo illustrate the changes of iodized salt usage, goiter rate of school-aged children and median urinary iodine concentration (MUIC) of school-aged children in Chongqing for the last 21 years. This study aims to estimate the variational provincial status of iodine nutrition and provide scientific evidence for fine-tuning and adaptation of the current program. MethodsDifferent number of families and school children aged 8–10 years from Chongqing during 1997–2018 participated in the study. UIC and iodine content in table salt were measured. Thyroid volumes of students were examined and goiter prevalence was calculated across years. ResultsThe median iodine content of table salt was negatively associated with years(r = −0.727, P < 0.01). The MUIC were decreased annually (ranged between 200 and 300 μg/L) and was negatively associated with year(r = −0.831, P < 0.01). Goiter of school-aged children in Chongqing was decreased from the highest rate of 23.58% in 1999 to 1.62% in 2018(Cochran-Armitage Trend Test: χ2=-30.695, P < 0.01). Thyroid volume were negatively associated with years(r = −0.962, P < 0.01) and had a positive relationship with MUIC 1997–2018 (r = 0.862, P < 0.01). ConclusionsThe consumption of adequately iodized salt can eliminate Iodine deficiency disorders (IDD) in children, but possible excessive iodine intake from salt could result in high urinary iodine excretion and even goiter. A systematic, well-designed and continual program monitoring is essential to ensure the adequacy of iodine fortification levels and to regularly change the iodine concentration in household table salt.

Urinary essential and toxic metal mixtures, and type 2 diabetes mellitus: Telomere shortening as an intermediary factor?

The joint effect of metal mixtures on telomere function and type 2 diabetes mellitus (T2DM) is unclear. This large-scale cross-sectional study sought to assess the role of telomere length (TL) in the relationship between urinary essential and toxic metal mixtures, and T2DM in 7410 Chinese adults ≥ 60 years of age. Essential (Cr, Cu, Zn, Se) and non-essential metals (V, Al, Sb, Sn, Cd, Pb) in urine samples were quantified, while leukocyte TL was measured from blood samples. Restricted cubic splines regression showed nonlinear relationships between single metal and T2DM, and between TL and T2DM. Bayesian kernel machine regression and quantile-based g-computation showed that the overall status of urinary metals was positively associated with risk of developing T2DM, which was mainly explained by exposure to Pb, Cd, and Sb, excessive Se intake, and high excretion of Zn. Mediation analyses showed that shortened TL mediated 27.9% of the overall positive effect of metal exposure on T2DM, and this mediation was mainly explained by toxic metal exposure and excessive Se intake. Tobacco smoke exposure, extensive cooking at home, and black tea consumption were found to be important contributors of toxic metal exposures. Further studies are needed to explore the recommended Zn dosage for T2DM patients at different stages, which may ameliorate pancreatic senescence and glycemic progression.

Achievement rate of target blood pressure in patients with hypertension treated by hypertension specialists and non-specialists in a real-world setting.

Hypertension remains a major global healthcare issue. Considering that most Japanese patients with hypertension are managed by general practitioners, hypertension specialists should be involved in actual clinical practice. We investigated the blood pressure (BP), guidelines recommended for achievement rate of the target BP, and clinical variables of patients with hypertension treated by hypertension specialists and those treated by non-specialists in a real-world setting. Factors associated with the target BP achievement in this population were also investigated. Outpatients with hypertension from 12 medical facilities in Okinawa Prefecture were enrolled (n = 1469 [specialist group, 794; non-specialist group, 675]; mean age, 64.2 years; females, 45.8%). For all patients, BP and rate of the target BP achievement were 129.0 ± 15.5/74.6 ± 10.6 mmHg, and 51.8%, respectively. BP and the rate of target of BP achievement were 128.0 ± 15.1/73.4 ± 10.4 mmHg and 56.7% in the specialist group, and they were 130.1 ± 15.9/76.0 ± 10.8 mmHg and 46.1% in the non-specialist group. The urinary salt excretion and obesity rates were comparable between the specialist and non-specialist groups. Multivariable logistic analyses indicated that hypertension specialists and good medication adherence were positive factors, whereas obesity, chronic kidney disease, diabetes mellitus, and urinary salt excretion were inverse factors associated with target BP achievement in this population. Initiatives for salt reduction, medication adherence, and proper obesity management are crucial to improving BP management in patients with hypertension. Hypertension specialists are expected to play an essential role in them. For all patients, the target blood pressure (BP) achievement rate were 51.8%. Hypertension specialists and good medication adherence were positive factors in achieving target BP; conversely, obesity, diabetes mellitus, chronic kidney disease, and high urinary salt excretion were inverse factors in achieving target BP among patients with hypertension.

Mycotoxins on edible insects: Should we be worried?

Edible insects are a solid alternative to meet the growing demand for animal protein. However, there are doubts regarding the safety of insect consumption. Mycotoxins are substances of concern for food safety, as they may cause harmful effects on the human organism and accumulate in the tissues of some animals. This study focuses on the characteristics of the main mycotoxins, the mitigation of human consumption of contaminated insects, and the effects of mycotoxins on insect metabolism. To date, studies reported the interaction of the mycotoxins aflatoxin B1, ochratoxin A, zearalenone, deoxynivalenol, fumonisin B1, and T-2, isolated or combined, in three insect species from Coleoptera and one from Diptera order. The use of rearing substrates with low mycotoxin contamination did not reduce the survival and development of insects. Fasting practices and replacing contaminated substrate with a decontaminated one decreased the concentration of mycotoxins in insects. There is no evidence that mycotoxins accumulate in the tissues of the insects' larvae. Coleoptera species showed high excretion capacity, while Hermetia illucens had a lower excretion capacity of ochratoxin A, zearalenone, and deoxynivalenol. Thus, a substrate with low mycotoxin contamination could be used for raising edible insects, particularly from the Coleoptera order.

Diagnostic policies on nephrolithiasis/nephrocalcinosis of possible genetic origin by Italian nephrologists: a survey by the Italian Society of Nephrology with an emphasis on primary hyperoxaluria

BackgroundPrimary hyperoxaluria is a genetic disorder of the metabolism of glyoxylate, the precursor of oxalate. It is characterized by high endogenous production and excessive urinary excretion of oxalate, resulting in the development of calcium oxalate nephrolithiasis, nephrocalcinosis, and, in severe cases, end-stage kidney disease and systemic oxalosis. Three different forms of primary hyperoxaluria are currently known, each characterized by a specific enzymatic defect: type 1 (PH1), type 2 (PH2), and type 3 (PH3). According to currently available epidemiological data, PH1 is by far the most common form (about 80% of cases), and is caused by a deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase.MethodsA survey on rare forms of nephrolithiasis and nephrocalcinosis with a focus on primary hyperoxaluria in the setting of Italian Nephrology and Dialysis Centers, using an online questionnaire, was recently conducted by the Project Group “Rare Forms of Nephrolithiasis and Nephrocalcinosis” of the Italian Society of Nephrology, with the aim of assessing the impact and management of this disorder in clinical practice in Italy.ResultsForty-five public and private Italian Centers participated in the survey, and responses to the questionnaire were provided by 54 medical professionals. The survey results indicate that 21 out of the 45 participating Centers are managing or have managed primary hyperoxaluria patients, most of whom are on dialysis, or are recipients of kidney transplants.ConclusionsThe data of this survey indicate the need to implement genetic testing in suspected cases of primary hyperoxaluria, not only in the setting of dialysis or transplantation, but also with the aim of encouraging early diagnosis of PH1, which is the only type of primary hyperoxaluria for which specific drug therapy is currently available.Graphical abstract

Is the 1mg-dexamethasone suppression test a precise marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas?

To analyze if the 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs). Cross-sectional study of patients with nonfunctioning adrenal incidentalomas (NFAIs, defined by cortisol post-DST ≤ 1.8 µg/dL) and patients with autonomous cortisol secretion (ACS, defined by cortisol post-DST > 1.8 µg/Dl). The urinary steroid profile (USP) was determined by gas chromatography coupled to mass spectrometry. Both groups were matched by sex, age and body mass index. Forty-nine patients with AIs (25 with ACS and 24 with NFAI) were included. As a whole, AIs showed a high excretion of β-cortolone, tetrahydro-11-deoxycortisol (THS), α-cortolone, α-cortol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE). A positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites (r = 0.401, P = 0.004) was observed, with the stronger being observed with total THS (r = 0.548, P < 0.001) and THF (r = 0.441, P = 0.002). Some of the metabolites that were elevated in patients with AIs, were higher in patients with ACS-related comorbidities than in those without comorbidities. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767 [95% CI 0.634-0.882]). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853 [0.712‒0.954]). The DST has a positive, but modest, correlation with urinary glucocorticoid excretion. Similarly, the diagnostic accuracy of the DST for the prediction of ACS-related comorbidities is only fair, but it may be improved if combined with the results of the USP and serum DHEAS. This is the first study aimed to evaluate if 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs) and if urinary steroid profile was measured by GS-MS could improve such a prediction. We found a positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites, with the stronger being observed with total tetrahydro-11-deoxycortisol (THS) and tetrahydrocortisol. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853).

Transient Pseudohypoaldosteronism: A Rare Cause of Severe Hyponatremia in a Baby

Hyponatremia and dehydration in children represent a medical emergency due to a variety of underlying illness. Other than an evidence of gastroenteritis with diarrhea and vomiting (which is the major cause of hypoosmolar hyponatremia in pediatric age), other causes should be considered, especially if there is evidence of hyperkalemia and high sodium fraction excretion (FENa), like iatrogenic causes (diuretic excess), transient or genetic abnormalities of the renal mineralocorticoid pathway, syndrome of inappropriate anti-diuretic hormone secretion (SIADH), acute renal failure, congenital adrenal hyperplasia (CAH).&#x0D; Here we present a case of transient pseudohypoaldosteronism in a 2 months old baby secondary to urinary tract infection, who presented with a history of poor sucking, fever and dehydration.

Phytoremediation potential modulated by structural and functional traits in a saline desert halophyte Fagonia indica Burm. f.

Using halophytes for phytoremediation is an environmentally friendly technique, now gaining importance all over the world. Fagonia indica Burm. f. (Indian Fagonia) is primarily distributed in salt-affected lands of the Cholistan Desert and surrounding habitats. Four populations with three replications from salt-affected habitats were collected from natural habitats to evaluate structural and functional adaptation for salinity tolerance and phytoremediation of hypersaline habitats. The populations collected from the highest saline sites Pati Sir (PS) and Ladam Sir (LS) had restricted growth habit, increased accumulation of K+ and Ca2+ along Na+ and Cl-, more excretion of Na+ and Cl-, increased cross-sectional area of root and stem, larger exodermal and endodermal cells in roots, and broad metaxylem area. Sclerification in stem was high in population. Specific modifications in leaves were reduced stomatal area and increased adaxial epidermal cell area. Important traits associated with phytoremediation potential of F. indica populations (Pati Sir and Ladam Sir) were deeper roots and taller plants, increased density of salt glands on leaf surface, and high excretion of Na+. Additionally, higher bio-concentration factor, translocation factor, and dilution factor for Na and Cl- in same Ladam Sir and Pati Sir population were identified as key phytoremediation attributes. The plants of F. indica colonizing high salinities (Pati Sir and Ladam Sir) were, therefore, more efficient in phytoremediation of saline soils as these populations accumulated and/or excrete toxic salts. Density of salt glands remarkably increased in the Pati Sir population collected from the highest salinity. This population accumulated and excreted the highest amount of Na+ and Cl-. The dilution factor of Na+ and Cl- ions was also the highest in this population. Anatomical modifications such as root and stem cross-sectional areas, proportion of storage parenchyma, and broad metaxylem vessels were the maximum in Pati Sir population. These modifications indicate not only better salt tolerance of the Pati Sir population but also better in accumulation and excretion of toxic salts. This population can potentially rehabilitate hypersaline uncultivated lands through green reclamation.

Increased renal elimination of endogenous and synthetic pyrimidine nucleosides in concentrative nucleoside transporter 1 deficient mice

Concentrative nucleoside transporters (CNTs) are active nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here we identify a role of CNT1 in the renal reabsorption of nucleosides. Deletion of CNT1 in mice increases the urinary excretion of endogenous pyrimidine nucleosides with compensatory alterations in purine nucleoside metabolism. In addition, CNT1 KO mice exhibits high urinary excretion of the nucleoside analog gemcitabine (dFdC), which results in poor tumor growth control in CNT1 KO mice harboring syngeneic pancreatic tumors. Interestingly, increasing the dFdC dose to attain an area under the concentration-time curve level equivalent to that achieved by wild-type (WT) mice rescues antitumor efficacy. The findings provide new insights into how CNT1 regulates reabsorption of endogenous and synthetic nucleosides in murine kidneys and suggest that the functional status of CNTs may account for the optimal action of pyrimidine nucleoside analog therapeutics in humans.

Urinary Copper Excretion Is Associated with Long-Term Graft Failure in Kidney Transplant Recipients

Introduction: In chronic kidney disease, proteinuria increases urinary copper excretion, inducing oxidative tubular damage and worsening kidney function. We investigated whether this phenomenon occurred in kidney transplant recipients (KTRs). In addition, we studied the associations of urinary copper excretion with the biomarker of oxidative tubular damage urinary liver-type fatty-acid binding protein (u-LFABP) and death-censored graft failure. Methods: This prospective cohort study was performed in the Netherlands between 2008 and 2017, including outpatient KTR with a functioning graft for longer than 1 year, who were extensively phenotyped at baseline. Twenty-four-hour urinary copper excretion was measured by inductively coupled plasma mass spectrometry. Multivariable linear and Cox regression analyses were performed. Results: In 693 KTR (57% men, 53 ± 13 years, estimated glomerular filtration rate [eGFR] 52 ± 20 mL/min/1.73 m²), baseline median urinary copper excretion was 23.6 (interquartile range 11.3–15.9) µg/24 h. Urinary protein excretion was positively associated with urinary copper excretion (standardized β = 0.39, p < 0.001), and urinary copper excretion was positively associated with u-LFABP (standardized β = 0.29, p < 0.001). During a median follow-up of 8 years, 109 (16%) KTR developed graft failure. KTR with relatively high copper excretion were at higher risk of long-term graft failure (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.32–1.86 per log₂, p < 0.001), independent of multiple potential confounders like eGFR, urinary protein excretion, and time after transplantation. A dose-response relationship was observed over increasing tertiles of copper excretion (HR: 5.03, 95% CI: 2.75–9.19, tertile 3 vs. 1, p < 0.001). u-LFABP was a significant mediator of this association (74% of indirect effect, p < 0.001). Conclusion: In KTR, urinary protein excretion is positively correlated with urinary copper excretion. In turn, higher urinary copper excretion is associated with an independent increased risk of kidney graft failure, with a substantial mediating effect through oxidative tubular damage. Further studies are warranted to investigate whether copper excretion-targeted interventions could improve kidney graft survival.