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Worldwide, as well as in Mexico, the leading cause of death is cardiovascular disease (CVD). Hypertension is the main risk factor for CVD; about 50% of the adult population suffers from this condition. High sodium (Na) intake combined with low potassium (K) intake can trigger cardiovascular disorders such as high blood pressure (BP). The aim of this study was to estimate the mean excretion of Na and K in Mexican adults using a spot urine sample, and its association with cardiovascular disorders. Information on 2,778 adults, 20-59 years of age, who participated in ENSANUT-2016 was analyzed. Na and K were estimated using Tanaka formulae. Biomarkers such as glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, and anthropometry were measured. Mean Na was 3,354 mg/day (95%CI: 3,278, 3,429), 1,440 mg/day of K (95%CI: 1,412, 1,469), and the Na-K ratio was 2.4. The excretion of Na was greater in adults with high BP (3,542 mg/day) compared to those with normal BP (3,296 mg/day). In adults with hypertension, excretion of K was 10% greater (1,534 mg/day) than in adults with normal BP (1,357 mg/day). In adults with moderate reduction of renal function, Na excretion was 22% less (2,772 mg/day) than in adults with normal kidney function (3,382 mg/day). The results of this study show that the cardiovascular health of Mexican adults is at risk, as they showed high Na excretion and low K excretion.

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Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

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Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies have suggested that it could play a role in regulating potassium renal excretion by modulating the activity of the Na+-Cl- cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal-potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low-potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1-/- mice had lower plasma levels of K+ and Cl- while exhibiting higher urinary excretion of Na+, Cl-, and K+ compared with KS-WNK1+/+ mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K+ levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1+/+ mice adapt better to HKD challenge than KS-WNK1-/- mice after a potassium-retaining state. The difference in the phosphorylated NCC-to-NCC ratio between KS-WNK1+/+ and KS-WNK1-/- mice after 0KD and HKD indicates a role for KS-WNK1 in both NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the distal convoluted tubule to respond to extreme changes in potassium intake, such as those occurring in wildlife.NEW & NOTEWORTHY The findings of this study demonstrate that kidney-specific with-no-lysine kinase 1 plays a role in regulating urinary electrolyte excretion during extreme changes in potassium intake, such as those occurring in wildlife. .

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Using diffusible iodine-based contrast-enhanced computed tomography (diceCT), we examined the morphology of the oral glands of 12 species of the family Homalopsidae. Snakes of this family exhibit substantial interspecific morphological variation in their oral glands. Particular variables are the venom glands, ranging from large (e.g., Subsessor bocourti) to small (e.g., Erpeton tentaculatum). The supra- and infralabial glands are more uniform in morphology, being the second most developed in almost all the sampled species. Premaxillary glands distinct from the supralabial glands were observed in five species (Myron richardsonii, Bitia hydroides, Cantoria violacea, Fordonia leucobalia, and Gerarda prevostiana), in addition to Cerberus rynchops, the only species in which this condition was previously documented associated with the excretion of salt. In the three species of the saltwater group of homalopsids (C. violacea, F. leucobalia, and G. prevostiana), the premaxillary glands also extend posteriorly, occupying a large area above the supralabial gland, a condition not observed in any other species of snake studied thus far. Character evolution analyses indicate that premaxillary glands differentiated from the supralabial gland and evolved independently three or four times in the family, always in lineages that invaded marine habitats. Our results suggest that the differentiated premaxillary glands are likely salt glands, as is the case in C. rynchops. If corroborated, this increases to six or seven the number of independent evolutionary origins of salt glands in snakes that have undergone an evolutionary transition to marine life.

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BACKGROUND: Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus (DM). It has been proposed that modifications in the function of proximal tubule epithelial cells (PTECs) precede glomerular damage during the onset of DKD. This study aimed to identify modifications in renal sodium handling in the early stage of DM and its molecular mechanism. METHODS: Streptozotocin (STZ)-induced diabetic BALB/c mice (STZ group) and LLC-PK1 cells, a model of PTECs, were used. All parameters were assessed in the 4th week after an initial injection of STZ. RESULTS: Early stage of DKD was characterized by hyperfiltration and PTEC dysfunction. STZ group exhibited increased urinary sodium excretion due to impairment of tubular sodium reabsorption. This was correlated to a decrease in cortical (Na++K+)ATPase (NKA) α1 subunit expression and enzyme activity and an increase in O-GlcNAcylation. RNAseq analysis of patients with DKD revealed an increase in expression of the glutamine-fructose aminotransferase (GFAT) gene, a rate-limiting step of hexosamine biosynthetic pathway, and a decrease in NKA expression. Incubation of LLC-PK1 cells with 10 µM thiamet G, an inhibitor of O-GlcNAcase, reduced the expression and activity of NKA and increased O-GlcNAcylation. Furthermore, 6-diazo-5-oxo-L-norleucine (DON), a GFAT inhibitor, or dapagliflozin, an SGLT2 inhibitor, avoided the inhibitory effect of HG on expression and activity of NKA associated with the decrease in O-GlcNAcylation. CONCLUSION: Our results show that the impairment of tubular sodium reabsorption, in the early stage of DM, is due to SGLT2-mediated HG influx in PTECs, increase in O-GlcNAcylation and reduction in NKA expression and activity.

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The higher availability of zinc (Zn) from organic than inorganic sources is already established, but more assertive and cost-friendly protocols on the total replacement of inorganic with organic Zn sources for laying hens still need to be developed. Because some discrepancy in the effects of this replacement in laying hen diets is noticeable in the literature, the objective of this meta-analysis was to properly quantify the effect size of total replacing inorganic Zn with organic Zn in the diet of laying hens on their laying performance, egg quality, and Zn excretion. A total of 2340 results were retrieved from Pubmed, Scielo, Scopus, WOS, and Science Direct databases. Of these, 18 primary studies met all the eligibility criteria and were included in this meta-analysis. Overall, the replacement of inorganic Zn with organic Zn, regardless of other factors, improved (p < 0.01) egg production by 1.46%, eggshell thickness by 0.01 mm, and eggshell resistance by 0.11 kgf/cm2. Positive results of the same nutritional strategy on egg weight and Zn excretion were only observed at specific conditions, especially when organic Zn was supplemented alone in the feed, not combined with other organic minerals. Therefore, there is evidence in the literature that the total replacement of inorganic Zn with organic Zn improves egg production, eggshell thickness, and eggshell resistance. Factors such as hen age and genetics, organic Zn source, concentration of Zn in the feed, and the strategy of its supplementation have to be more carefully considered in protocols designed to address egg weight and Zn excretion by the hen.

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Frogs evolved terrestrial development multiple times, necessitating mechanisms to avoid ammonia toxicity at early stages. Urea synthesis from ammonia is a key adaptation that reduces water dependence after metamorphosis. We tested for early expression and plasticity of enzymatic mechanisms of ammonia detoxification in three terrestrial-breeding frogs: foam-nest-dwelling larvae of Leptodactylus fragilis (Lf) and arboreal embryos of Hyalinobatrachium fleischmanni (Hf) and Agalychnis callidryas (Ac). Activity of two ornithine-urea cycle (OUC) enzymes, arginase and CPSase, and levels of their products urea and CP in tissues were high in Lf regardless of nest hydration, but reduced in experimental low- vs. high-ammonia environments. High OUC activity in wet and dry nests, comparable to that under experimental high ammonia, suggests terrestrial Lf larvae maintain high capacity for urea excretion regardless of their immediate risk of ammonia toxicity. This may aid survival through unpredictably long waiting periods before rain enables their transition to water. Moderate levels of urea and CP were present in Hf and Ac tissues and enzymatic activities were lower than in Lf. In both species, embryos in drying clutches can hatch and enter the water early, behaviorally avoiding ammonia toxicity. Moreover, glutamine synthetase was active in early stages of all three species, condensing ammonia and glutamate to glutamine as another mechanism of detoxification. Enzyme activity appeared highest in Lf, although substrate and product levels were higher in Ac and Lf. Our results reveal that multiple biochemical mechanisms of ammonia detoxification occur in early life stages of anuran lineages that evolved terrestrial development.

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Primary production underpins most ecosystem services, including carbon sequestration and fisheries. Artificial reefs (ARs) are widely used for fisheries management. Research has shown that a mechanism by which ARs in seagrass beds can support fisheries and carbon sequestration is through increasing primary production via fertilization from aggregating fish excretion. Seagrass beds are heavily affected by anthropogenic nutrient input and fishing that reduces nutrient input by consumers. The effect of these stressors is difficult to predict because impacts of simultaneous stressors are typically non-additive. We used a long-term experiment to identify the mechanisms by which simultaneous impacts of sewage enrichment and fishing alter seagrass production around ARs across non-orthogonal gradients in human-dominated and relatively unimpacted regions in Haiti and The Bahamas. Merging trait-based measures of seagrass and seagrass ecosystem processes, we found that ARs consistently enhanced per capita seagrass production and maintained ecosystem-scale production despite drastic shifts in controls on production from human stressors. Importantly, we also show that coupled human stressors on seagrass production around ARs were additive, contrasting expectations. These findings are encouraging for conservation because they indicate that seagrass ecosystems are highly resistant to coupled human stressors and that ARs promote ecosystem services even in human-dominated ecosystems.

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Higher salt (sodium) intake has been associated with higher blood pressure (BP). The degree of association may be influenced by factors such as age, origin, and dietary components. This study aimed to evaluate the 24 h urinary sodium (Na) and potassium (K) excretion in normotensive and hypertensive Dominican adults and estimate their salt intake. 163 volunteers (18-80 years old) participated in a cross-sectional study. The 24 h Na and K urinary excretion were measured using an ion-selective electrode technique. Na and K urinary excretion (99.4 ± 46.5 and 35.0 ± 17.5 mmol/24 h) did not correlate with BP, except in the normotensive group, in which K correlated with SBP (0.249, p = 0.019). Na and K excretion were similar in normotensive and hypertensive subjects. When considering two age groups (18-45, 46-80 years), the Na-to-K molar ratio (3.1 ± 1.3) was higher in younger subjects (p = 0.040). Na-to-K ratio was associated with DBP in the total group (r = 0.153, p = 0.052), in the hypertensive group (r = 0.395, p < 0.001), and in the older group with SBP (0.350, p = 0.002) and DBP (0.373, p < 0.001). In the older group, Na-to-K ratio and DBP correlated after controlling for subjects with hypertension controlled by treatment (r = 0.236, p = 0.041). The Na-to-K ratio correlated, when salt intake was over 5 g/day (52.2%), with SBP (rho = 0.219, p = 0.044) and DBP (rho = 0.259, p = 0.017). Determinants of BP in the total sample were age (SBP, beta: 0.6 ± 0.1, p < 0.001; DBP, beta: 0.2 ± 0.1, p < 0.002), sex (SBP, beta: 11.2 ± 3.5, p = 0.001), body mass index (BMI) (SBP, beta: 1.0 ± 0.3, p < 0.001; DBP, beta: 0.4 ± 0.2, p = 0.01), and Na-to-K ratio (SBP, beta: 3.0 ± 1.1, p = 0.008; DBP, beta: -12.3 ± 4.0, p = 0.002). Sex and BMI were determinants in the younger group. Na-to-K molar ratio was determinant in the older group (SBP, beta: 6.7 ± 2.4, p = 0.005; DBP, beta: 3.8 ± 1.1, p < 0.001). The mean Na and salt intakes (2.3 and 5.8 g/day) were slightly higher and the K intake lower (1.4 g/day) than WHO recommendations.

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This work aimed to evaluate the total, unbound, renal, and hepatic clearances of raltegravir (RAL) and the formation and elimination clearances of raltegravir glucuronide (RAL GLU) in pregnant women living with HIV. The participants received RAL 400 mg twice daily during the third trimester (n = 15) of gestation, delivery (n = 15), and the postpartum period (n = 8). Pharmacokinetic parameter values were calculated on the basis of plasma and urine data using noncompartmental methods. RAL clearances for the third trimester of gestation were as follows: total clearance: geometric mean, 63.63 L/h (95% CI, 47.5-85.25); renal clearance: geometric mean, 2.56 L/h (95% CI, 1.96-3.34); hepatic clearance: geometric mean, 60.52 L/h (95% CI, 44.65-82.04); and unbound clearance: geometric mean, 281.14 L/h (95% CI, 203.68-388.05). RAL GLU formation and elimination clearances for the third trimester of gestation were 7.57 L/h (95% CI, 4.94-11.6) and 8.71 L/h (95% CI, 6.71-11.32), respectively. No differences were observed in RAL GLU pharmacokinetic parameters between the third trimester of gestation and the postpartum period, except for higher formation (7.57 vs 4.03 L/h) and elimination (8.71 vs 4.92 L/h) clearances during the third trimester. The findings based on plasma and urine data are consistent with an increase in the hepatic uridine 5' diphospho-glucuronosyltransferase isoenzymes activities involved in RAL metabolism during pregnancy, and the formation of RAL GLU is a minor route of RAL elimination. Compared to the postpartum period, in the third trimester of gestation, the similar RAL plasma exposure in pregnant women reinforces the maintenance of an RAL regimen including a 400-mg oral dose twice daily during pregnancy.

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