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International Journal of Molecular... Aug 2021Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from... (Review)
Review
Molecular Biological and Clinical Understanding of the Pathophysiology and Treatments of Hyperuricemia and Its Association with Metabolic Syndrome, Cardiovascular Diseases and Chronic Kidney Disease.
Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Disease Management; Disease Susceptibility; Humans; Hyperuricemia; Metabolic Syndrome; Renal Insufficiency, Chronic; Severity of Illness Index
PubMed: 34502127
DOI: 10.3390/ijms22179221 -
American Journal of Physiology. Renal... Mar 2019Dietary oxalate is plant-derived and may be a component of vegetables, nuts, fruits, and grains. In normal individuals, approximately half of urinary oxalate is derived... (Review)
Review
Dietary oxalate is plant-derived and may be a component of vegetables, nuts, fruits, and grains. In normal individuals, approximately half of urinary oxalate is derived from the diet and half from endogenous synthesis. The amount of oxalate excreted in urine plays an important role in calcium oxalate stone formation. Large epidemiological cohort studies have demonstrated that urinary oxalate excretion is a continuous variable when indexed to stone risk. Thus, individuals with oxalate excretions >25 mg/day may benefit from a reduction of urinary oxalate output. The 24-h urine assessment may miss periods of transient surges in urinary oxalate excretion, which may promote stone growth and is a limitation of this analysis. In this review we describe the impact of dietary oxalate and its contribution to stone growth. To limit calcium oxalate stone growth, we advocate that patients maintain appropriate hydration, avoid oxalate-rich foods, and consume an adequate amount of calcium.
Topics: Calcium; Calcium Oxalate; Calcium, Dietary; Diet; Humans; Kidney Calculi; Oxalates
PubMed: 30566003
DOI: 10.1152/ajprenal.00373.2018 -
Frontiers in Pediatrics 2022Human fetal and neonatal bilirubin metabolism is centered on -bilirubin IXα (BR) due to the extremely low BR conjugating capacity of the liver. BR is a unique, highly... (Review)
Review
Human fetal and neonatal bilirubin metabolism is centered on -bilirubin IXα (BR) due to the extremely low BR conjugating capacity of the liver. BR is a unique, highly lipophilic substance with physiological and toxic effects in the cell membranes of organs and body tissues. The fetus excretes BR through the placenta to the maternal circulation. After birth, BR is thought to act as an antioxidant against the increase in reactive oxygen species caused by the rapid increase in oxygen concentration during the adaptation process from in amniotic fluid to in air. However, bilirubin encephalopathy is a toxic effect of bilirubin. Due to the lipophilic nature of BR, it must be bound to a carrier to be distributed to various parts of the body by hydrophilic blood. This carrier of BR is human serum albumin (HSA). In humans, BR can be excreted efficiently after undergoing photochemical reactions upon high affinity binding to HSA. HSA also plays an important role in the prevention of bilirubin encephalopathy. This review focuses on the developmental and physiological role of bilirubin metabolism during the fetal and neonatal periods.
PubMed: 36824297
DOI: 10.3389/fped.2022.1002408 -
Revista Panamericana de Salud Publica =... 2022To determine the 24-hour urinary sodium and potassium excretions in the Americas. (Review)
Review
OBJECTIVE
To determine the 24-hour urinary sodium and potassium excretions in the Americas.
METHODS
A systematic review and meta-analysis were performed seeking for studies conducted between 1990 and 2021 in adults living in any sovereign state of the Americas in Medline, Embase, Scopus, SciELO, and Lilacs. The search was first run on October 26, 2020 and was updated on December 15, 2021. Of 3 941 abstracts reviewed, 74 studies were included from 14 countries, 72 studies reporting urinary sodium (27 387 adults), and 42 studies reporting urinary potassium (19 610 adults) carried out between 1990 and 2020. Data were pooled using a random-effects meta-analysis model.
RESULTS
Mean excretion was 157.29 mmol/24h (95% CI, 151.42-163.16) for sodium and 57.69 mmol/24h (95% CI, 53.35-62.03) for potassium. When only women were considered, mean excretion was 135.81 mmol/24h (95% CI, 130.37-141.25) for sodium and 51.73 mmol/24h (95% CI, 48.77-54.70) for potassium. In men, mean excretion was 169.39 mmol/24h (95% CI, 162.14-176.64) for sodium and 62.67 mmol/24h (95% CI, 55.41-69.93) for potassium. Mean sodium excretion was 150.09 mmol/24h (95% CI, 137.87-162.30) in the 1990s and 159.79 mmol/24h (95% CI, 151.63-167.95) in the 2010s. Mean potassium excretion was 58.64 mmol/24h (95% CI, 52.73-64.55) in the 1990s and 56.33 mmol/24/h (95% CI, 48.65-64.00) in the 2010s.
CONCLUSIONS
These findings suggest that sodium excretions are almost double the maximum level recommended by the World Health Organization and potassium excretions are 35% lower than the minimum requirement; therefore, major efforts to reduce sodium and to increase potassium intakes should be implemented.
PubMed: 36406293
DOI: 10.26633/RPSP.2022.199 -
Biological Reviews of the Cambridge... Apr 2022Honeydew is the sugar-rich excretion of phloem-feeding hemipteran insects such as aphids, mealybugs, whiteflies, and psyllids, and can be a main carbohydrate source for... (Review)
Review
Honeydew is the sugar-rich excretion of phloem-feeding hemipteran insects such as aphids, mealybugs, whiteflies, and psyllids, and can be a main carbohydrate source for beneficial insects in some ecosystems. Recent research has revealed that water-soluble, systemic insecticides contaminate honeydew excreted by hemipterans that feed on plants treated with these insecticides. This contaminated honeydew can be toxic to beneficial insects, such as pollinators, parasitic wasps and generalist predators that feed on it. This route of exposure has now been demonstrated in three plant species, for five systemic insecticides and four hemipteran species; therefore, we expect this route to be widely available in some ecosystems. In this perspective paper, we highlight the importance of this route of exposure by exploring: (i) potential pathways through which honeydew might be contaminated with insecticides; (ii) hemipteran families that are more likely to excrete contaminated honeydew; and (iii) systemic insecticides with different modes of action that might contaminate honeydew through the plant. Furthermore, we analyse several model scenarios in Europe and/or the USA where contaminated honeydew could be problematic for beneficial organisms that feed on this ubiquitous carbohydrate source. Finally, we explain why this route of exposure might be important when exotic, invasive, honeydew-producing species are treated with systemic insecticides. Overall, this review opens a new area of research in the field of ecotoxicology to understand how insecticides can reach non-target beneficial insects. In addition, we aim to shed light on potential undescribed causes of insect declines in ecosystems where honeydew is an important carbohydrate source for insects, and advocate for this route of exposure to be included in future environmental risk assessments.
Topics: Animals; Aphids; Carbohydrates; Ecosystem; Humans; Insecta; Insecticides
PubMed: 34802185
DOI: 10.1111/brv.12817 -
American Journal of Physiology. Renal... Aug 2020We investigated the regulation of Na and K excretion and the epithelial Na channel (ENaC) in mice lacking the gene for aldosterone synthase (AS) using clearance methods...
We investigated the regulation of Na and K excretion and the epithelial Na channel (ENaC) in mice lacking the gene for aldosterone synthase (AS) using clearance methods to assess excretion and electrophysiology and Western blot analysis to test for ENaC activity and processing. After 1 day of dietary Na restriction, AS mice lost more Na in the urine than AS mice did. After 1 wk on this diet, both genotypes strongly reduced urinary Na excretion, but creatinine clearance decreased only in AS mice. Only AS animals exhibited increased ENaC function, assessed as amiloride-sensitive whole cell currents in collecting ducts or cleavage of αENaC and γENaC in Western blots. To assess the role of aldosterone in the excretion of a K load, animals were fasted overnight and refed with high-K or low-K diets for 5 h. Both AS and AS mice excreted a large amount of K during this period. In both phenotypes the excretion was benzamil sensitive, indicating increased K secretion coupled to ENaC-dependent Na reabsorption. However, the increase in plasma K under these conditions was much larger in AS animals than in AS animals. In both groups, cleavage of αENaC and γENaC increased. However, Na current measured ex vivo in connecting tubules was enhanced only in AS mice. We conclude that in the absence of aldosterone, mice can conserve Na without ENaC activation but at the expense of diminished glomerular filtration rate. Excretion of a K load can be accomplished through aldosterone-independent upregulation of ENaC, but aldosterone is required to excrete the excess K without hyperkalemia.
Topics: Animals; Cytochrome P-450 CYP11B2; Epithelial Sodium Channels; Kidney Tubules, Collecting; Mice; Natriuresis; Potassium; Sodium; Sodium, Dietary
PubMed: 32628540
DOI: 10.1152/ajprenal.00204.2020 -
Journal of Animal Science and... Nov 2023Ruminants play a critical role in our food system by converting plant biomass that humans cannot or choose not to consume into edible high-quality food. However,... (Review)
Review
Ruminants play a critical role in our food system by converting plant biomass that humans cannot or choose not to consume into edible high-quality food. However, ruminant excreta is a significant source of nitrous oxide (NO), a potent greenhouse gas with a long-term global warming potential 298 times that of carbon dioxide. Natural phytochemicals or forages containing phytochemicals have shown the potential to improve the efficiency of nitrogen (N) utilization and decrease NO emissions from the excreta of ruminants. Dietary inclusion of tannins can shift more of the excreted N to the feces, alter the urinary N composition and consequently reduce NO emissions from excreta. Essential oils or saponins could inhibit rumen ammonia production and decrease urinary N excretion. In grazed pastures, large amounts of glucosinolates or aucubin can be introduced into pasture soils when animals consume plants rich in these compounds and then excrete them or their metabolites in the urine or feces. If inhibitory compounds are excreted in the urine, they would be directly applied to the urine patch to reduce nitrification and subsequent NO emissions. The phytochemicals' role in sustainable ruminant production is undeniable, but much uncertainty remains. Inconsistency, transient effects, and adverse effects limit the effectiveness of these phytochemicals for reducing N losses. In this review, we will identify some current phytochemicals found in feed that have the potential to manipulate ruminant N excretion or mitigate NO production and deliberate the challenges and opportunities associated with using phytochemicals or forages rich in phytochemicals as dietary strategies for reducing N excretion and excreta-derived NO emissions.
PubMed: 37941085
DOI: 10.1186/s40104-023-00942-0 -
The Journal of Clinical Investigation Mar 1973Normal subjects and patients with antidiuretic hormone (ADH) deficiency were studied to determine the mechanism of the antidiuretic action of clofibrate. Before...
Normal subjects and patients with antidiuretic hormone (ADH) deficiency were studied to determine the mechanism of the antidiuretic action of clofibrate. Before clofibrate treatment, the patients' ability to concentrate urine with a standardized dehydration procedure correlated with the amount of ADH which was excreted. During clofibrate administration all six patients with ADH deficiency developed an antidiuresis which was like that of ADH, since there was no change in sodium, potassium, total solute, or creatinine excretion. There was a correlation between the patients' ability to concentrate urine during dehydration and the subsequent response to clofibrate, and the excretion of ADH during dehydration correlated with the excretion of ADH on clofibrate therapy. Clofibrate-induced antidiuresis in these patients was partially overcome by ethanol and by water loading. Clofibrate interfered with the ability of patients and subjects to excrete a water load and prevented the water load from inhibiting ADH excretion in the normal subjects. These studies suggested that clofibrate was acting through endogenous ADH and this thesis was supported by the failure of clofibrate to produce an antidiuresis when injected into rats with total ADH deficiency (Brattleboro strain) although an antidiuresis was produced in water-loaded normal rats. When the drug was injected into Brattleboro rats with exogenous ADH, clofibrate either did not alter or it inhibited the action of the ADH. The data demonstrate that clofibrate has a significant ADH-like action. This action appears to be mediated through the release of endogenous ADH.
Topics: Adult; Animals; Clofibrate; Creatinine; Dehydration; Diabetes Insipidus; Diuresis; Drinking; Ethanol; Female; Humans; Male; Middle Aged; Osmolar Concentration; Potassium; Rats; Sodium; Urination; Vasopressins
PubMed: 4685079
DOI: 10.1172/JCI107213 -
The Journal of Neuroscience : the... Apr 2018Steroids play vital roles in animal physiology across species, and the production of specific steroids is associated with particular internal biological functions. The... (Review)
Review
Steroids play vital roles in animal physiology across species, and the production of specific steroids is associated with particular internal biological functions. The internal functions of steroids are, in most cases, quite clear. However, an important feature of many steroids (their chemical stability) allows these molecules to play secondary, external roles as chemical messengers after their excretion via urine, feces, or other shed substances. The presence of steroids in animal excretions has long been appreciated, but their capacity to serve as chemosignals has not received as much attention. In theory, the blend of steroids excreted by an animal contains a readout of its own biological state. Initial mechanistic evidence for external steroid chemosensation arose from studies of many species of fish. In sea lampreys and ray-finned fishes, bile salts were identified as potent olfactory cues and later found to serve as pheromones. Recently, we and others have discovered that neurons in amphibian and mammalian olfactory systems are also highly sensitive to excreted glucocorticoids, sex steroids, and bile acids, and some of these molecules have been confirmed as mammalian pheromones. Steroid chemosensation in olfactory systems, unlike steroid detection in most tissues, is performed by plasma membrane receptors, but the details remain largely unclear. In this review, we present a broad view of steroid detection by vertebrate olfactory systems, focusing on recent research in fishes, amphibians, and mammals. We review confirmed and hypothesized mechanisms of steroid chemosensation in each group and discuss potential impacts on vertebrate social communication.
Topics: Animal Communication; Animals; Chemoreceptor Cells; Humans; Nonverbal Communication; Pheromones, Human; Social Behavior; Steroids
PubMed: 29519850
DOI: 10.1523/JNEUROSCI.2488-17.2018 -
Nature Communications Feb 2023Anthropogenic pressures are restructuring coral reefs globally. Sound predictions of the expected changes in key reef functions require adequate knowledge of their...
Anthropogenic pressures are restructuring coral reefs globally. Sound predictions of the expected changes in key reef functions require adequate knowledge of their drivers. Here we investigate the determinants of a poorly-studied yet relevant biogeochemical function sustained by marine bony fishes: the excretion of intestinal carbonates. Compiling carbonate excretion rates and mineralogical composition from 382 individual coral reef fishes (85 species and 35 families), we identify the environmental factors and fish traits that predict them. We find that body mass and relative intestinal length (RIL) are the strongest predictors of carbonate excretion. Larger fishes and those with longer intestines excrete disproportionately less carbonate per unit mass than smaller fishes and those with shorter intestines. The mineralogical composition of excreted carbonates is highly conserved within families, but also controlled by RIL and temperature. These results fundamentally advance our understanding of the role of fishes in inorganic carbon cycling and how this contribution will change as community composition shifts under increasing anthropogenic pressures.
Topics: Animals; Temperature; Coral Reefs; Fishes; Carbonates; Anthropogenic Effects; Anthozoa; Ecosystem
PubMed: 36813767
DOI: 10.1038/s41467-023-36617-7