Low Excretion Research Articles

Taste Preference for Salt Predicts Salt Intake in a Chinese Population.

This study describes the association between taste preference for salt and actual salt intake, thus guiding and refining personal and public health campaigns designed to lower salt intake in China. A cross-sectional survey of 1489 residents aged 18 to 69 years was conducted in 2017 in China. A multistage random sampling strategy was used, and a combination of questionnaires and physical and laboratory measurements were conducted to collect baseline characteristics and knowledge, attitudes, and behavior (KAB) related to salt. A 24 h urine collection was obtained for sodium and potassium excretion analysis. Participants were divided into two groups, light taste preference and salty taste preference, according to their answer to the question "Compared to others, how do you think your taste preference is for salt?". The mean age of the 1489 participants was 46.26 years, 48.9% were males, over 1/3 (35.7%) were identified as hypertensive, and 317 (21.3%) self-reported a salty taste preference. The mean of 24 h urinary sodium excretion was 167.32 mmol/24 h, corresponding to 9.79 g salt/d intake, and the sodium-to-potassium ratio (Na/K) was 4.90. The 24 h urinary sodium excretion of salty taste preference (177.06 mmol/24 h) was significantly higher than that of light taste preference (164.69 mmol/24 h). The multiple logistic regression analysis showed that the salty taste preference group had significantly higher 24 h urinary sodium (ORa(95%CI) = 1.004(1.002-1.006)), diastolic blood pressure (DBP), proportion of greasy food preference, and drinking levels, but lower potassium excretion, response levels to most KAB questions, and regular physical activity compared to the light taste preference group. Self-reported taste preference for salt predicted actual salt intake, which was verified by 24 h urinary sodium monitoring. Taste preference for salt could be used as a proxy for intake in terms of targeted salt intake, nutrition, and health education.

Inorganic phosphate additives in meals and adaptations to 5-days of dietary inorganic phosphate loading alter acute calcium homeostasis in two randomized cross-over studies in healthy adults.

Diets containing inorganic phosphate additives are unbalanced with respect to calcium and these diets have been linked to the development of altered bone metabolism. Using 2 randomized cross-over studies in healthy humans, we (1) characterized the hormonal and urinary response to 2 meals with the same reported phosphorus amount (562-572mg), where one was manufactured with inorganic phosphate additives and a comparatively lower Ca:P molar ratio (0.26 vs 0.48), and (2) assessed how acute homeostatic mechanisms adapt following 5-d exposure to recommended dietary phosphorus amount (~700mg P/d) compared to a diet enriched with inorganic phosphate additives (~1100mg P/d). Participants were then challenged with 500mg of oral phosphorus in the form of inorganic phosphate after an overnight fast following each diet condition. Measurements included serum calcium, phosphate, PTH, and fibroblast growth factor 23 , vitamin D metabolites, and urine calcium and phosphate excretion. Following the meal containing inorganic phosphate additives with a low Ca:P ratio, serum phosphate was higher and more phosphate was excreted in the urine compared to the low additive meal. Although the Ca:P and calcium content was lower in the high additive meal, the same amount of calcium was excreted into the urine. Subsequently, increasing only dietary phosphate through additives resulted in lower 24-h excretion of calcium. The oral phosphate challenge promoted urinary calcium excretion, despite no consumption of calcium, which was attenuated when pre-acclimated to a high phosphate diet. These data suggest that ingestion of inorganic phosphate promotes calcium excretion, but homeostatic mechanisms may exist to reduce calcium excretion that are responsive to dietary intake of phosphate. Future studies are required to evaluate potential implication of diets enriched with inorganic phosphate additives on bone health.

Analysis of Urinary Iodine Concentration in Differentiated Thyroid Cancer and Breast Cancer Cases.

This study aimed to analyze the correlation between urinary iodine concentration in differentiated thyroid cancer (DTC) and breast cancer (BC) subjects. The study consisted of 80 subjects divided into case (20 DTC and 20 BC subjects) and control (40 subjects). Morning urine or spot urine was used for UIC measurement. In thyroid cancer, UIC median patients and controls were 195.45 ± 133.61 µg/L and 145 ± 39.64 µg/L, respectively, with p =0.33. The UIC median of PTC subjects was significantly higher compared to FTC subjects, 227.12±130.98 μg/L versus 68.75±22.95 μg/L, p=0.00, and papillary thyroid cancer is closely related to a high iodine excretion in urine with contingency coefficient (c)=0.722. In BC patients, regardless of subtypes, breast cancer subjects showed a significantly lower iodine excretion level. The median of UIC patients and controls were 80.05 ± 38.24 µg/L and 144.25 ± 36.79 µg/L, respectively, p=0.000. Iodine urine concentrations strongly correlate with the type of DTC histopathology, and in BC subjects, IUC was significantly lower compared to the control.

Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation

The urinary mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) are short-term biomarkers of exposure from acrylamide and its metabolite glycidamide, respectively. The medium-term exposure to acrylamide and glycidamide is monitored by the adducts N-(2-carbamoylethyl)-Val (AA-Val) and N-(2-carbamoyl-2-hydroxyethyl)-Val (GA-Val) in hemoglobin (Hb), respectively. Three questions were addressed by application of these biomarkers in two diet studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any warmed or heated food for at least four months): first, what is the internal acrylamide exposure following a vegan or a raw food diet in comparison to that in omnivores? Second, did the exposure change between 2017 and 2021? And third, what is the stability over time of AAMA/GAMA excretion compared to that of AA-Val/GA-Val levels in Hb between both time points? Median urinary AAMA excretion per day in non-smoking omnivores, vegans and raw food eaters were 62.4, 85.4 and 15.4 µg/day, respectively; the corresponding median AA-Val levels were 27.7, 39.7 and 13.3 pmol/g Hb, respectively. Median levels in strict raw food eaters were about 25% (AAMA excretion) and 48% (AA-Val) of those in omnivores. In comparison to 2017, AAMA and GAMA excretion levels were hardly altered in 2021, however, levels of AA-Val and GA-Val in 2021 slightly increased. There was a weak correlation between AAMA excretion levels determined four years apart (rS = 0.30), and a moderate correlation between levels of AA-Val (rS = 0.55) in this timeframe. Our data in strict raw food eaters confirm a significant endogenous formation to acrylamide in a size range, which is—based on the levels of AA-Val—distinctly higher than reported previously based on levels of urinary AAMA excretion. The relatively lower AAMA excretion in raw food eaters likely represents a lower extent of glutathione conjugation due to missing hepatic first-pass metabolism in case of endogenous formation of acrylamide, which leads to a higher systemic exposure.

#963 Discrepancy between actual and estimated urine creatinine excretion predicts mortality in chronic kidney disease: from the KNOW-CKD study

Abstract Background and Aims Urine creatinine excretion is a surrogate marker of muscle mass and low urine creatinine excretion is a predictor of poor clinical outcome. There are several methods to estimate urine creatinine excretion. However, little is known about the clinical implication of discrepancy between actual and estimated urine creatinine excretion in chronic kidney disease (CKD). The aim of this study is to investigate the association between actual and estimated urine creatinine excretion discrepancy and mortality in CKD. Method This study analysed 1805 participants from the KNOW-CKD cohort. They underwent 24-hr urine collection and measured urine creatinine excretion at baseline. Their estimated urine creatinine excretion was calculated by Joachim's method. Discrepancy between actual and estimated urine creatinine excretion (dUCr) was defined as actual urine creatinine excretion minus estimated urine creatinine excretion. Patients were divided into 3 groups according to their tertile of dUCr. The study endpoint was all-cause death. Results During a follow-up of 13 062 person-years (median 8.0 years), 151 patients (8.4%) died, with a corresponding death rate of 11.6 (95% CI 9.9-13.6) per 1000 patients-years. 86 (14.4%), 41 (6.8%) and 24 (3.4%) patients from each 1st to 3rd tertile of dUCr died (P < 0.001). In multivariate Cox proportional hazard analysis, there was a graded association of dUCr with all-cause mortality. The adjusted hazard ratios (95% CI) of 2nd and 3rd tertile were 0.58 (0.39-0.86) and 0.36 (0.22-0.58) compared with the 1st tertile. Conclusion Higher discrepancy between actual and estimated urine creatinine excretion is associated with lower risk of mortality in predialysis CKD patients. This association was independent of various conventional and CKD-related risk factors.

#1865 The role of osteoclast-associated receptor in phosphorus metabolism via salivary-bone-kidney interaction

Abstract Background and Aims We have identified osteoclast-associated receptor (OSCAR) in the osteoclasts and salivary proline-rich proteins (S-PRPs), which are specifically secreted from the salivary glands and are carrier proteins for calcium and phosphorus, as new factors involved in phosphorus metabolism using bulk RNA sequencing of all organs in a high-phosphate (HP) loaded mouse model with kidney disease. The roles of OSCAR have been reported to include activation of NFATc1, which is essential for osteoclast differentiation, and inhibition of apoptosis. However, to our knowledge, no study has examined the relationship between OSCAR and chronic kidney disease-mineral bone disorder (CKD-MBD). In this study, we investigated the role of OSCAR in phosphorus metabolism particularly involving the salivary grands (S-PRPs) in mice models of high phosphorus load and kidney disease. Method We used 11- to 13-week C57BL/6N male mice to compare phosphorus metabolism between wild-type (WT) and OSCAR knockout (KO) mice. WT and OSCAR KO mice underwent sham surgery (Ctrl group) or 5/6 nephrectomy (CKD group), followed by HP loading (1.8% phosphate diet) for 1 week. After HP loading, these mice were kept in metabolic gauges for 24 hours, during which urine and fecal samples were collected. Subsequently, blood and organ (parotid grand and kidney) samples were collected. The parotid grands, the main source of S-PRPs, were harvested after 1 week of HP loading, and specific mRNA for S-PRPs (Prb1 and Prpmp5) and for phosphate (Pi) transporter (NaPi2b and Pit-2), responsible for Pi reabsorption in primary saliva, were examined. Results In the non-CKD group, there were no significant difference in Pi homeostasis including plasma Pi, FGF23, PTH, or urinary, fecal, and salivary Pi excretion levels after HP loading. In the CKD group, OSCAR KO mice showed significantly lower urinary Pi excretion than WT mice (WT vs OSCAR KO; 25.43 ± 3.88 mg/day vs 17.65 ± 5.75 mg/day, P = .006) after HP loading, but no difference in fecal Pi excretion was seen between genotypes. HP-induced plasma intact and C-terminal FGF-23 elevations were significantly suppressed in OSCAR KO mice (WT vs OSCAR KO; 6857 ± 4484 pg/mL vs 1573 ± 524 pg/mL, P = .002), indicating that the increased FGF23 “production” was suppressed in HP-loaded CKD/OSCAR KO mice. In contrast, there was no difference in plasma PTH levels between OSCAR KO and WT mice (WT vs OSCAR KO; 4189 ± 1361 pg/mL vs 5082 ± 1120 pg/mL, P = .22). As a result, plasma Pi levels in WT mice were not significantly different from those in OSCAR KO mice after 1-week HP loading (WT vs OSCAR KO; 26.91 ± 7.76 mg/dL vs 28.87 ± 7.49 mg/dL, P = 0.61), suggesting an increased internal Pi burden to organs other than the blood stream such as bones and ectopic calcifications in OSCAR KO mice compared to WT mice after HP loading and CKD. In the parotid gland, S-PRPs encoding mRNA (Prb1 and Prpmp5) expressions were decreased in OSCAR KO mice compared to those in WT mice, with or without CKD. Pi reabsorption transporter mRNA expression in the parotid gland was also decreased in OSCAR KO mice compared to those in WT mice, with or without CKD, after 1-week HP loading, suggesting an increase in salivary Pi concentrations in OSCAR KO mice compared to WT mice. Conclusion These results suggest that OSCAR may regulate urinary Pi excretion via FGF-23 in the bone. OSCAR was also significantly associated with salivary Pi levels via S-PRPs and Pi transporter in the parotid grands. OSCAR regulate Pi homeostasis through interactions with the kidney, salivary grands, bone, and intestine.

Exploring the therapeutic benefits of paliperidone in the management of schizophrenia: A promising approach for the mental well-being of this population

Paliperidone is a safe and effective option for the treatment of schizophrenia, with long-acting oral or intramuscular administration. Its low hepatic metabolization and renal excretion minimize complications in patients with pre-existing liver disease, providing greater adherence and therapeutic efficacy. The current study is a literature review, with an active search for “Paliperidone” and “Schizophrenia” on national and international platforms. Twenty-one articles were analyzed in the PubMed and Scielo databases. Twenty-one articles were selected based on an evaluation of the title, abstract and relevance to the study. The period of publication ranged from 2007 to 2024, and all were organized in terms of title, authorship, year of publication and methodology used. The data shows the consistent efficacy of paliperidone in relieving schizophrenic symptoms, its safety and tolerability, highlighting its ability to improve patients' quality of life. Although adverse events were observed, these were generally mild and did not compromise the continuity of treatment. In summary, the data support paliperidone as an effective and safe therapeutic option for schizophrenia, with the potential to improve patients' clinical and psychosocial outcomes. Paliperidone is an effective and well-tolerated option for treating schizophrenia, with studies indicating improved patient compliance and clinical stability. Its low incidence of serious side effects increases long-term safety. This reduces relapse and hospitalization rates, improving quality of life.

Evaluation of protocols to determine urine output and urinary urea nitrogen excretion in dairy cows with and without dietary salt supplementation

Urine output and urinary urea-N excretion (UUNe) excretion are critical measures to accurately evaluate N metabolism in lactating dairy cows and environmental concerns related to manure N. The objectives of this study were: (1) to compare estimates of UUNe, urine output, and related variables from 3 pre-established measurement protocols (bladder catheterization, external collection cup, and spot sampling) and from dietary salt supplementation, (2) to study temporal variation in UUNe, urine output, and related variables as affected by measurement protocol, and (3) to evaluate urine specific gravity as a predictor of urine output. Twelve multiparous Holstein cows were used in a split-plot, Latin square design. Cows were randomly assigned to a diet (main plot) containing either 0.7% or 1.6% NaCl (DM basis) and then assigned to a sequence of 3 protocols (subplot) in a balanced 3 × 3 Latin square with 14-d period. For each protocol, measurements were conducted every 4 h for 3 consecutive days. Urine output was determined gravimetrically for bladder catheterization and external collection cup or based on measured cow BW, measured urinary creatinine concentration, and the assumed creatinine excretion of 29 mg/kg BW per day for spot sampling. Urine specific gravity was measured by refractometry. When averaged over a 3-d measurement period and compared with bladder catheterization, spot sampling underestimated urine output (6.8 kg/d; 20%) and UUNe (26 g/d; 13%) but exhibited greater concentration of urinary urea-N (+58 mg/dL; 10%). There were no differences in any measurements determined via bladder catheterization or external cup device protocols, except for urine output that tended to be 3.7 kg/d lower for collection cup compared with bladder catheterization. The 2 gravimetric protocols yielded lower urinary creatinine concentration than spot sampling (64.7 vs. 88.1 mg/dL) and lower creatinine excretion (25.3 mg/kg BW per day) than the value of 29 mg/kg BW per day generally assumed in the spot sampling protocol. Salt supplementation tended to increase urine output (+5.2 kg/d) and decrease urinary urea-N concentration (-93 mg/dL), urinary creatinine concentration (-9.5 mg/dL), milk protein concentration (-0.19 percentage unit) and milk protein yield (-70 g/d). There was greater temporal variation of urine output when measured via the collection cup compared with bladder catheterization in the first 2 d but not the third day of sampling, suggesting that an extended period of adaptation might have improved data quality of the collection cup protocol. The R2 of the linear regression to predict urine output with urine specific gravity was 67%, 73%, and 32% for bladder catheterization, collection cup, and spot sampling, respectively. In this study, spot sampling underestimated both urine output and UUNe, but UUNe determination did not differ between external collection cup and bladder catheterization. However, our data suggested the need to investigate the adaptation protocol, required days of measurements and the conversion of urine mass to urine volume to improve accuracy and precision of urine collection protocols.

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Effect of dietary treatments on performance, oocysts shedding and lesion scores in broiler chickens experimentally challenged with Eimeria infection

Although anticoccidials effectively control coccidiosis, a needed reduction in the reliance on antimicrobials in animal production leads to the exploration of alternative compounds. The present study aimed to test five different dietary treatments to counteract the negative impact of coccidiosis on broiler chickens’ health and performance. 1-day-old male Ross 308 broilers (n = 960) were randomly assigned to one of eight treatments, with six cages per treatment (20 birds/cage). To the diet of the broiler chickens of treatments (Trt) 1–5, a synbiotic was added from d0-10. From d10–28, birds of Trt1 and Trt2 were fed synbiotics, whereas birds of Trt3 were fed diets with glutamine, and birds of Trt4 and Trt5 were fed diets with a combination of β-glucans and betaine. From d28-35 onwards, birds of Trt1 were fed a diet with a synbiotic, whereas birds of Trt2-4 received diets with glutamine, and birds of Trt5 were fed a non-supplemented diet. Birds of the positive control group (PC; Trt6) were fed a standard diet supplemented with an anticoccidial (Decoquinate). The challenged negative control (NCchall; Trt7) and non-challenged negative control (NC) Trt8 were fed a standard diet without anticoccidial or other dietary treatment. At 7 days (d) of age, all birds were inoculated with 1 023, 115, and 512 sporulated oocysts of E. acervulina, E. maxima, and E. tenella, respectively, except for Trt8. Body weight gain (BWG), feed intake, and feed conversion ratio were assessed for each feeding phase (d0-10, d10-28 and d28-35) and overall experimental period (d0-35). Oocyst shedding, Eimeria lesion scores, cecal length, and relative weight were assessed at d13, d22, d28 and d35. Additionally, oocyst shedding was determined at d9 and d17. Litter quality was evaluated at d27 and d34, and footpad lesions at d34. During the starter (d0-10) and finisher (d28-35) periods, performance did not differ between the treatments. During the grower period (d10-28), Trt6 (PC) and Trt8 (NC) chickens had the highest BWG of all treatments (P < 0.001). Dietary treatment had no effect on litter quality and severity of footpad lesions. In the PC group (Trt6), low oocyst excretion and lesion scores were found. When comparing Trt1-5 with NCchall (Trt7), none of the treatments significantly reduced oocyst output or lesion scores. In conclusion, in this experiment, none of the dietary treatments performed similar or better compared to the PC group (Trt6) regarding performance or reducing Eimeria oocyst shedding or lesion scores.

Evaluation of renal sodium handling in heart failure with preserved ejection fraction: A pilot study.

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.

POTASSIUM-ENRICHED SALT EFFECTIVELY REDUCES SODIUM INTAKE IN THE NURSING HOME POPULATION OF NORTHERN CHINA: THE CHINA SALT TRIAL

Objective: to explore the promoting effect of long-term consumption of potassium-enriched salt (KCL/NACL=1:1) on dietary salt restriction in the nursing home population. Design and method: In northern China, a total of 29 nursing homes were selected using cluster random sampling. The nursing homes were divided into intervention group (using potassium-enriched salt in the dining room) and control group (using regular salt in the dining room). The usage of salt and high-sodium condiments in the dining room was recorded, including the amount of salt used and the number of diners. The average per capita daily sodium intake from condiments (TNA/PD) in the nursing home was calculated, as well as the average per capita daily sodium intake from dietary salt (SNA/PD). The two values were added together to calculate the total per capita daily sodium intake (ANA/PD). Results: Over 6 years, a total of 18,046 meals were consumed in the dining room. The intervention group demonstrated a significant reduction in per capita daily sodium intake (ANA/PD) compared to the control group (3.0 vs 5.0g). There was no statistically significant difference in per capita daily sodium intake from condiments (TNA/PD) between the two groups, but the intervention group exhibited a significantly lower per capita daily sodium intake from dietary salt (SNA/PD) compared to the control group (2.2 vs 4.1g). Furthermore, the intervention group consistently maintained a lower urine sodium-to-potassium ratio than the control group. By incorporating potassium-enriched salt, the intervention group achieved an average increase of 1.2±0.31g in daily potassium intake. Subgroup analysis of 24-hour urine results indicated that the intervention group had significantly lower urinary sodium excretion and higher potassium excretion. Following one year of using potassium-enriched salt, the estimated dietary salt intake in the intervention group decreased from approximately 15g to around 9g based on urinary sodium excretion. Conclusions: These findings suggest that the utilization of potassium-enriched salt can effectively reduce sodium intake without necessitating alterations in dietary habits.

Renal potassium regulation in a pig model of therapeutic hypothermia

Therapeutic hypothermia is increasingly utilized clinically to reduce tissue metabolism and protect against neurological damage in cases of cardiac arrest, traumatic brain injury or perinatal hypoxic ischemia. With even mild exposure to hypothermia, hypokalemia develops purportedly due to transcellular potassium shifts resulting in decreased circulating potassium levels. Renal dysfunction with body temperature cooling has also been postulated to potentially contribute to development of sustained hypokalemia. In this study, we used a pig model of controlled acute hypothermia without confounding hypotension and hypoxemia, to test the hypothesis that renal handling of potassium remains intact in hypothermia and is not the cause of decreased circulating plasma potassium seen with body cooling. Anesthetized, mechanically ventilated Duroc cross young pigs (n=25, body weight = 10.0 ± 0.4 kg, male or female) were catheterized for hemodynamic monitoring, regional blood flow assessment via colored microspheres, and urine collection. After baseline values were obtained, pigs were divided into a control normothermia group (n=12) with body temperature maintained at 38.4 ± 0.1 oC or a hypothermia group (n=13) with core body temperature cooled to 34.5 ± 0.1 oC and hypothermia sustained for 2 hours. Hypothermia reduced tissue metabolism as indicated by a decrease in oxygen consumption (VO2= 5.2 ± 0.2 ml/kg in normothermia vs 3.7 ± 0.3 ml/kg in hypothermia. Mean arterial pressure (68± 3 mm Hg) and cardiac output (199 ± 21 ml/min/kg) were not different between groups. Even with the short duration of cold exposure, plasma potassium was lower (p&lt;0.05) within 2 hours of hypothermia (4.1 ± 0.1 mEq/L) vs control (4.8 ± 0.1 mEq/L). Cold exposure caused redistribution of blood flow to the small intestines from other internal organs. Renal blood flow tended to decrease with cold, but glomerular filtration rate was suffcient to maintain urine flow, sodium excretion and free water clearance. Potassium clearance, however, was lower (p&lt;0.05) in hypothermia (0.70 ± 0.07 ml/min/kg) than in normothermia (1.04 ± 0.07 ml/min/kg), with lower potassium excretion (hypothermia = 2997 ± 331 mEq/min vs control = 4784 ± 393 mEq/min, p&lt;0.05) and fractional excretion of potassium. Reduced renal potassium excretion is consistent with renal compensation for lower circulating potassium induced by hypothermia. Interestingly, with relatively higher blood flow to the small intestines compared to decreased blood flow of other internal organs, potassium secretion in the early colon may contribute to further potassium wasting in hypothermia. The rapid initiation of decreased potassium circulating levels with hypothermia supports the thesis of temperature sensitive cell membrane potassium channels affecting extracellular to intracellular shifts of potassium. Results of this study indicate that renal potassium regulation is maintained in hypothermia and functions to decrease urinary potassium loss in the face of hypokalemia. The views expressed are those of the authors and do not necessarily reflect the offcial policy or position of the Defense Health Agency, Department of the Army, Department of Defense, or the U.S. Government. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Comparative Analysis of Fractional Excretion of Sodium, Potassium and Magnesium among T2DM Patients with Increased Albuminuria and Normal Albuminuria in a Tertiary Care Hospital- An Observational Study

Background: T2DM often leads to diabetic kidney disease, a condition marked by change in GFR and urinary albumin excretion. The renal handling of key electrolytes like sodium, potassium, and magnesium plays a crucial role in the progression of renal tubulointerstitial damage in diabetic patients. Aim of the study: The aim of this study was to compare the fractional excretion of sodium, potassium and magnesium among T2DM patients with increased albuminuria and normal albuminuria. Methods: This observational study was conducted in Department of Nephrology, Chattogram, Bangladesh from February 2021 to January 2022. Total 125 patients with T2DM were included in this study. Result: Baseline characteristics showed no significant differences across the study groups. Biochemically, eGFR decreased non-significantly from 95.5 to 86.1 ml/min/1.73 m² across groups, while UACR significantly increased from 14.3 to 1056 mg/gm (P&lt;0.001). FBG levels were similar, but 2hPPBG showed a significant decrease from 8.2 to 7.4 mmol/l (P=0.0041). HbA1C levels varied slightly. FENa, FEK, and FEMg showed significant differences across groups, with FENa ranging from 0.59% to 0.56% (P=0.0016), FEK from 9.4% to 6.9% (P=0.0358), and FEMg from 2.87% to 5.58% (P=0.001). Correlations revealed significant negative associations of eGFR with FENa, FEK, and FEMg, and a significant positive correlation of FEMg with UACR. No significant correlations were found between FBG, 2hPPBG, HbA1C, and the electrolytes excretion. Conclusion: Significant variations in the fractional excretion of sodium, potassium, and magnesium were observed. Higher eGFR was associated with lower electrolyte excretion, and a significant positive correlation was found between magnesium excretion and UACR.

Low Cortisone as a Novel Predictor of the Low-Renin Phenotype.

To evaluate low cortisone as a predictor of low renin activity and its association with parameters of kidney and vascular damage. A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low plasma renin activity (<1 ng/mL × hours) and low cortisone (<25th percentile). Plasma renin activity was associated with aldosterone (r = 0.36; P < .001) and cortisone (r = 0.22; P = .001). A binary logistic regression analysis showed that serum cortisone per ug/dL increase predicted the low-renin phenotype (OR 0.4, 95% CI 0.21-0.78). The receiver operating characteristic curves for cortisone showed an area under the curve of 0.6 to discriminate subjects with low renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (P < .05). This is the first study showing that low cortisone is a predictor of a low-renin condition. Low cortisone also predicted surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the aldosterone-renin ratio calculation.

Effects of manganese glycine on eggshell quality, eggshell ultrastructure, and elemental deposition in aged laying hens

Poor eggshell quality of eggs laid by aged laying hens is the major problem affecting the length of the rearing period in the laying hen industry. Trace elements are required and play vital roles in the eggshell quality of laying hens. Appropriate dose of organic microelements is environmentally friendly and sufficient to satisfy the needs of hens because of their greater bioavailability and lower excretion than inorganic forms. The aim of this experiment was to investigate the effects of manganese (Mn) glycine (MG) on eggshell quality, elemental deposition, and eggshell ultrastructure in aged laying hens. A total of 720 Hy-Line Brown hens 70 weeks old were assigned equally to four groups with six replicates of 30 birds each. The hens were fed basal diets (without Mn supplementation) supplemented with 120 mg/kg of Mn from manganese sulfate monohydrate (MSM), or 40, 80, or 120 mg/kg Mn from MG for 12 weeks. Dietary supplementation with 80 mg/kg Mn from MG resulted in the greatest eggshell strength after 6 weeks of treatment (P = 0.047), and in greater eggshell strength than observed in the MSM control after 12 weeks of treatment (P = 0.025). After 12 weeks of treatment, the eggs of hens in the MG groups showed lower mammillary layer thickness in the blunt end, equator, and acute end than observed in the MSM control group (P < 0.001). With the exception of the blunt ends of eggs from hens in the 120 mg/kg MG group, the eggs of hens in the MG groups, compared with the MSM control group, exhibited a lower mammillary layer ratio, and greater palisade layer ratio and effective layer ratio in the blunt end, equator, and acute end (P < 0.001). Dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control and 40 and 120 mg/kg MG, resulted in the greatest palisade layer thickness and effective layer thickness, and the lowest mammillary layer thickness in the equator (P < 0.001, P = 0.001, P < 0.001, respectively). Furthermore, supplementation with 80 mg/kg Mn from MG exhibited the greatest ratio of the palisade layer and effective layer, and the lowest mammillary layer ratio in the blunt end and equator (all P < 0.001). The Mn content of eggshells in hens-fed diets supplemented with 80 and 120 mg/kg Mn from MG was greater than that in the MSM control and 40 mg/kg MG groups (P = 0.035). Dietary supplementation with 80 or 120 mg/kg Mn from MG resulted in greater tibia Mn content than observed in the 40 mg/kg MG group (P = 0.019), and greater yolk Mn content than observed in the 40 mg/kg MG and MSM control groups (P = 0.018). In conclusion, dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control (120 mg/kg Mn), may increase the deposition efficiency of Mn, alter eggshell elemental composition, improve eggshell ultrastructure, and enhance eggshell strength in aged laying hens.

The effect of supplementary selenium source on apparent and true absorption, retention, performance, and selenium status in lactating Holstein cows

Selenium is an essential trace mineral for dairy cattle and can be provided in the diet in various forms that may differ in bioavailability. The objective of this study was to determine how source of Se affects animal performance, Se status, retention, and apparent and true absorption. Multiparous Holstein cows (n = 24; 597 ± 49 kg body weight) were blocked by days in milk (DIM; 161 ± 18) and randomly assigned to receive 0.3 mg Se/kg of dry matter (100% of NASEM requirements) of either organic Se (ORG; selenized yeast) or inorganic Se (INO; sodium selenite). The Se premix was top-dressed on a common total mixed ration fed daily and mixed into the top 15 cm directly before feeding. Following an 11-wk adaptation period, cows received simultaneous infusions of an intraruminal isotope dose of 77Se in the same chemical form as the premix, and an intravenous dose of 82Se in an inorganic form. Infusions were followed by a 4-d period of blood and rumen fluid sampling, and total collection of feces, urine, and milk. Daily dry matter intake (23 ± 0.6 kg), milk yield (35 ± 1.2 kg), and serum Se (0.11 ± 0.003 µg/g) were not different between treatments during the adaptation period, but milk Se concentrations were greater for ORG compared with INO. Serum 77Se maximum concentration (Cmax) and area under the curve (AUC) were not different between treatments for 72 h following infusion, but rumen fluid 77Se AUC was higher for ORG than INO. Apparent absorption (64 ± 1.4%), and retention (44 ± 1.5%) of the 77Se dose did not differ between treatments. True absorption was calculated using 82Se enrichment in serum and feces and was determined to be 69 ± 1.3% and did not differ between treatments. Fecal excretion of the 77Se dose was not different between treatments (36 ± 1.4%), but ORG had lower urinary excretion and higher milk excretion compared with INO. These results indicate that organic Se resulted in greater Se concentration of milk and lower urinary Se excretion into the environment, but absorption, Se status, and performance of the cow were not affected by Se source at this supplementation level.

Effects of low-quality forage and starter protein content in starter diet of young calves on growth performance, rumen fermentation, and urinary purine derivatives.

Feeding low-quality forage (LQF) has been evaluated in mature ruminants and results show that it has been improved nitrogen utilization efficiency. The present study evaluated the interaction effect of feeding wheat straw as LQF (0 and 7.5%, DM basis) and starter protein level (20 vs. 24%, DM basis) on growth performance, ruminal fermentation, and microbial protein synthesis in Holstein dairy calves raised under moderate heat stress condition. Forty-eight 3-day old dairy calves (averaging 40.6 kg) were assigned in four experimental treatments as follow; 1) no LQF with 20% CP (NLQF-20CP), 2) no LQF with 24% CP (NLQF-24CP), 3) 7.5% LQF with 20% CP (LQF-20CP) and 4) 7.5% LQF and 24% CP (LQF-24CP). The calves were weaned on d 53 of age but the experiment extended until d 73 of age. Feeding LQF increased starter intake, average daily gain (tendency), ruminal acetate concentration, and improved fecal score of calves. The average daily gains before and after weaning were positively influenced with greater starter protein content. Hence, weaning and final BWs were improved when calves received greater CP content. In addition, greater starter CP content increased total ruminal volatile fatty acid concentration. With respect to the interaction effect between LQF feeding and starter protein content, the lower nitrogen excretion through urine was obtained for LQF-20CP diet among experimental treatments. The results of the current study showed that feeding LQF improved ruminal fermentation pattern and improved growth performance through increased starter intake. In addition, greater starter protein content is advisable during pre-weaning period for calves raised under mild heat stress condition. In conclusion, based on the results found in the current study, it can be suggested that feeding LQF for calves under heat stress condition can improve nitrogen utilization when dietary protein content is low. This can be opportunity to formulate starter diets with greater nitrogen utilization efficiency which is critical for accelerated growth programs at early stages of growth for young calves while calves raised under hot season condition.

Cadmium neurotoxicity and therapeutic strategies.

Cadmium (Cd) is a multitarget, carcinogenic, nonessential environmental pollutant. Due to its toxic effects at very low concentrations, lengthy biological half-life, and low excretion rate, exposure to Cd carries a concern. Prolonged exposure to Cd causes severe injury to the nervous system of both humans and animals. Nevertheless, the precise mechanisms responsible for the neurotoxic effects of Cd have yet to be fully elucidated. The accurate chemical mechanism potentially entails the destruction of metal-ion homeostasis, inducing oxidative stress, apoptosis, and autophagy. Here we review the evidence of the neurotoxic effects of Cd and corresponding strategies to protect against Cd-induced central nervous system injury.

An Epigenome-Wide Association Study of DNA Methylation and Proliferative Retinopathy over 28 Years in Type 1 Diabetes

To perform a prospective epigenome-wide association study of DNA methylation (DNAm) and 28-year proliferative diabetic retinopathy (PDR) incidence in type 1 diabetes (T1D). Prospective observational cohort study. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset (< 17 years) T1D. Stereoscopic fundus photographs were taken in fields 1, 2, and 4 at baseline, 2, 4, 6, 8, 16, 23, and 28 years after DNAm measurements. The photos were graded using the modified Airlie House System. In those free of PDR at baseline (n=265; mean T1D duration of 18 years at baseline), whole blood DNAm (EPIC array) at 683 597 CpGs was analyzed in Cox models for time to event. Associations between significant CpGs and clinical risk factors were assessed; genetic variants associated with DNAm were identified (methylation quantitative trait loci [meQTLs]). Mendelian randomization was used to examine evidence of causal associations between DNAm and PDR. Post hoc regional and functional analyses were performed. Proliferative diabetic retinopathy was defined as the first instance of a grade of ≥ 60 in at least 1 eye or pan-retinal photocoagulation for PDR. Follow-up time was calculated from the study visit at which DNAm data were available (baseline) until PDR incidence or censoring (December 31, 2018 or last follow-up). PDR incidence was 53% over 28-years' follow-up. Greater DNAm of cg27512687 (KIF16B) was associated with reduced PDR incidence (P=6.3×10-9; false discovery rate [FDR]: < 0.01); 113 cis-meQTLs (P<5×10-8) were identified. Mendelianrandomization analysis using the sentinel meQTL as the instrumental variable supported a potentially causal association between cg27512687 and PDR. Cg27512687 was also associated with lower pulse rate and albumin excretion rate and higher estimated glomerular filtration rate, but its association with PDR remained independently significant after adjustment for those factors. In regional analyses, DNAm of FUT4, FKBP1A, and RIN2 was also associated with PDR incidence. DNA methylation of KIF16B, FUT4, FKBP1A, and RIN2 was associated with PDR incidence, supporting roles for epigenetic regulation of iron clearance, developmental pathways, and autophagy in PDR pathogenesis. Further study of those loci may provide insight into novel targets for interventions to prevent or delay PDR in T1D. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.