Plasma Ca Research Articles

A Perspective On A Promising Role For Caffeine In Modulating The Casr In Pancreatic Β-Cells

The extracellular calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that plays a crucial role in the parathyroid glands and kidneys in maintaining calcium (Ca2+) homeostasis. The extracellular CaSR is present in various cell types not implicated in controlling plasma Ca2+ levels. There is accumulating evidence that CaSR plays a significant role in regulating the function of β-cells in the pancreas. Divalent cations and insulin are released together during exocytosis, and their concentration in the restricted intercellular compartments of the pancreatic islet increases to activate CaSR in neighboring cells. Subsequently, the activated CaSR stimulates insulin vesicle release in the adjacent cells, and by repeating these steps, the signal is amplified in the whole islet. Recent work developed a photoaffinity-tagged glutathione derivative (DAZ-G) as a chemical tool. The study demonstrated that DAZ-G can identify and analyze CaSR ligands. The use of DAZ-G identified caffeine as a positive allosteric modulator of the CaSR, suggesting that the physiological effects of caffeine are partly attributed to its stimulation of the CaSR. Future work may utilize caffeine to activate the CaSR in pancreatic β-cells to improve their secretory function

Calcium propionate is an alkalizing agent in exercising Standardbreds

The objective of this study was to determine if calcium propionate is an alkalizing agent in exercising Standardbreds and if it alters plasma glucose and serum insulin concentrations. This study used a randomized crossover design to test the hypotheses that calcium propionate alters total CO2 (tCO2), Ca++, pH, strong ion difference (SID), glucose, and insulin in Standardbreds completing a simulated race test (SRT) on a high-speed equine treadmill. Blood was collected from eight horses (mean age ± SD = 16 ± 2.7 years; range = 13 - 21 years) at 10 and 5 min prior to treatment or control administration, just prior to the subsequent SRT, directly after the SRT, and at 60- and 90-min post SRT. Plasma pH and plasma concentrations of tCO2, glucose, Ca++, and Na+, K+, Cl-, Lac- (for SID calculation) were measured in duplicate by blood gas analyzer and serum insulin by radioimmunoassay. Data were analyzed by two-way repeated-measures ANOVA. For plasma pH, Na+, K+, Cl-, Lac-, SID, insulin and glucose, no effects of treatment or treatment by sampling-timepoint interaction were found (p>0.05). Plasma tCO2, Ca++, pH, Na+, SID, and glucose concentrations were significantly lower, and Lac- was significantly higher, directly after the SRT compared to all other timepoints (p<0.05). Plasma tCO2, HCO3- and Ca++ were significantly higher in treated than in control horses at multiple sampling timepoints after treatment/control administration (p<0.05). Serum insulin concentration, measured only pre and 30 min post treatment/control administration, was unaffected by treatment. Calcium propionate is an alkalizing agent in horses.

Influence of N- and/or P-restriction on bone metabolism in young goats.

Ruminants can recycle nitrogen (N) and phosphorus (P), which are essential for vital body processes. Reduced N- and P-intake in ruminants is desirable for economic and ecologic reasons. Simultaneous modulation of mineral homoeostasis and bone metabolism occurs in young goats. This study aimed to investigate potential effects of dietary N- and/or P-restriction on molecular changes in bone metabolism. The twenty-eight young male goats were fed a control diet, an N-reduced diet, a P-reduced diet or a combined N- and P-reduced diet for 6-8 weeks. The N-restricted goats had lower plasma Ca concentration and higher plasma osteocalcin (OC) and CrossLaps concentrations. The P-restricted goats had reduced plasma inorganic phosphate (Pi) concentrations and increased plasma Ca concentrations. Due to the initiation of a signalling pathway that inhibits the fibroblast growth factor 23 (FGF23) expression, this was lower with P-restriction. Consequently, lower Pi concentrations were the main factor influencing the reduction in FGF23. The changes in mineral homoeostasis associated with P-restriction led to a reduction in OC, bone mineral content and mineral density. Simultaneously, bone resorption potentially increased with P-restriction as indicated by an increased receptor activator of NF-κB ligand/osteoprotegerin (OPG) ratio and an increase in OPG mRNA expression. Additionally, the increased mRNA expression of the calcitonin receptor during P-restriction points to a higher number of osteoclasts. This study demonstrates an impairment of bone remodelling processes in young goats by N- or P-restriction. With P-restriction, bone mineralisation rate was potentially reduced and bone quality impaired, while with N-restriction, bone remodelling increased.

Lactobacilli-Based Pro and Postbiotic Efficacy Are Also Influenced by Other Factors Than Dietary Challenging Conditions.

The present study aimed to confirm the previously reported 'recovery' effect to a challenging diet (CD) of a Lactobacilli-based probiotic (Pro) and its derived postbiotic (Post) in broilers. Identical diet compositions were used, and observations were extended to a second CD diet. A completely randomised block design of 2 × 3 treatment groups with two CDs and three additive conditions (Control, Pro, Post) was used. One additional group received a standard diet (SD). The study involved 1600 one-day-old Ross 308 male broilers. All diets, fed from d1 to 35, were formulated to contain identical nutrients levels, with CDs formulated to be greater than SD in nonstarch polysaccharides using rye and barley (Rye CD) or dry distiller grains with soluble, sunflower and rapeseed meal (DDGS CD). Growth performance parameters, footpad lesions (FPL) score and plasma Ca, P and uric acid concentrations were measured. Compared to SD, birds fed Rye CD and DDGS CD had a higher 1-35 days feed conversion ratio (+3.4 and +4.1%, respectively), due to a higher feed intake for Rye CD (+2.9%) and a lower body weight for DDGS CD (-4.1%). An effect of additive was restricted to Rye CD where Post depressed BW at d28 and d35 (-3.7 and -2.4%, respectively). Compared to Rye CD, DDGS CD lowered plasma Ca/P at d21 (-9.0%) and d35 (-8.1%) and uric acid at d21 (-26%). Pro increased plasma Ca in Rye CD at d21 (+12%) and Post decreased plasma uric acid in DDGS CD at d35 (-25%). All other plasma parameters were not affected. The previously observed recovery effect of a commercial probiotic and postbiotic were not reproducible under highly similar growth conditions, which suggests that both may have specific physiological effects which are only expressed under specific circumstances.

Higher Plasma Copper Exposure was Adversely Associated with Skeletal Muscle Indicators in Chinese Children Aged 6-9 Years: A Cross-Sectional Study.

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height2 (Ht2) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children.

Au-modified ceria nanozyme prevents and treats hypoxia-induced pulmonary hypertension with greatly improved enzymatic activity and safety

BackgroundDespite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown.ResultsIn this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca2+ level, and blood biochemical parameters were not affected.ConclusionWe conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension.Graphical

Effect of Dietary Energy Level during Late Gestation on Mineral Contents in Colostrum, Milk, and Plasma of Lactating Jennies.

This study investigated the effects of dietary energy levels during late gestation on mineral content in the plasma, colostrum, and milk of jennies postpartum. Twenty-four pregnant multiparous DeZhou jennies, aged 6.0 ± 0.1 years, with a body weight of 292 ± 33 kg, an average parity number of 2.7 ± 0.1, and similar expected dates of confinement (74 ± 4 days), were randomly allocated to three groups and fed three diets: high energy (12.54 MJ/kg, HE), medium energy (12.03 MJ/kg, ME), and low energy (11.39 MJ/kg, LE). Blood samples were collected from the jugular vein of each jenny at time points of 0 h, 24 h, 48 h, 5 d, 7 d, and 14 d after parturition. Additionally, milk samples were collected through manual milking, and an analysis of the mineral content was conducted. The results showed that compared with HE, both ME and LE significantly increased the levels of calcium (Ca), phosphorus (P), zinc (Zn), selenium (Se), molybdenum (Mo), and cobalt (Co) in the plasma and Ca, P, magnesium (Mg), copper (Cu), manganese (Mn), Zn, selenium (Se), molybdenum (Mo), and Co in the milk of jennies postpartum (p < 0.05); ME also increased the levels of potassium (K), iron (Fe), and Mn in plasma and K and Fe in milk (p < 0.05). The levels of Ca, K, Mg, P, Fe, Cu, Mn, Co, Se, Zn, and Mo in plasma and milk gradually decreased with increasing postpartum time. Their contents were the highest at 0 h postpartum, rapidly decreased after 24 h postpartum, and declined to the lowest on day 14 postpartum. The interaction between dietary energy level and postpartum time showed that although the concentrations of the minerals Ca, P, K, Mg, Fe, Cu, Mn, Zn, Co, Se, and Mo decreased in jennies' plasma and milk in the treatment groups with different energy levels as postpartum time increased, the pattern of change was also influenced by dietary energy level. The influence of dietary energy level in late gestation on the mineral content of milk and plasma during the postpartum colostrum phase was higher than that during the milk phase. In conclusion, this study demonstrated that, under the current experimental conditions, the mineral content of the colostrum, milk, and plasma of jennies after parturition was dependent on the dietary energy level during late gestation.

Exposure to neonicotinoid pesticides induces physiological disorders and affects color performance and foraging behavior in goldfish.

We investigated the effects of neonicotinoid pesticides (NEOs) on the spontaneous swimming and foraging behavior, as well as the morphological and physiological changes of goldfish. Most fish reared in thiamethoxam (THM)-sprayed rice fields showed the scales easily peeled off, and increased ascites. Some individuals showed decreased bio-defense activity and low plasma Ca2+. Similar changes were found in the exposure test to THM (1.0 and 20.0 μg/L) and dinotefuran (1.2 and 23.5 μg/L). Next, the effects of a low concentration of THM (1.0 μg/L) on the spontaneous swimming and foraging behavior of fish were examined. Fish exposed to THM for 1 week became restless and had increased the swimming performance, especially under natural light, white LED lighting and blue LED lighting. Goldfish exposed to THM had also increased intake of shiny white beads under green LED illumination. These results indicate that the exposure to NEO, even for a short period and at low levels, not only suppressed bio-defense activities and metabolic abnormalities, but also stress response, the swimming and foraging behavior of the fish are likely to be significantly suffered.

Vitamin D3 suppresses Npt2c abundance and differentially modulates phosphate and calcium homeostasis in Npt2a knockout mice

Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a−/− mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a−/− mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a−/− mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a−/− mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a−/− only, the latter might facilitate the increase in plasma Pi in Npt2a−/− mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3.

Risk factors associated with intraoperative persistent hypotension in pancreaticoduodenectomy.

Intraoperative persistent hypotension (IPH) during pancreaticoduodenectomy (PD) is linked to adverse postoperative outcomes, yet its risk factors remain unclear. To clarify the risk factors associated with IPH during PD, ensuring patient safety in the perioperative period. A retrospective analysis of patient records from January 2018 to December 2022 at the First Affiliated Hospital of Nanjing Medical University identified factors associated with IPH in PD. These factors included age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities, medication history, operation duration, fluid balance, blood loss, urine output, and blood gas parameters. IPH was defined as sustained mean arterial pressure < 65 mmHg, requiring prolonged deoxyepinephrine infusion for > 30 min despite additional deoxyepinephrine and fluid treatments. Among 1596 PD patients, 661 (41.42%) experienced IPH. Multivariate logistic regression identified key risk factors: increased age [odds ratio (OR): 1.20 per decade, 95% confidence interval (CI): 1.08-1.33] (P < 0.001), longer surgery duration (OR: 1.15 per additional hour, 95%CI: 1.05-1.26) (P < 0.01), and greater blood loss (OR: 1.18 per 250-mL increment, 95%CI: 1.06-1.32) (P < 0.01). A novel finding was the association of arterial blood Ca2+ < 1.05 mmol/L with IPH (OR: 2.03, 95%CI: 1.65-2.50) (P < 0.001). IPH during PD is independently associated with older age, prolonged surgery, increased blood loss, and lower plasma Ca2+.

Dynamic responses of blood metabolites to nutrient depletion and repletion in broiler chicken nutrition

A total of 720 male Cobb 500 broiler chicks were used in a 5 treatment and 8 replicate experiment to explore dynamic changes in blood metabolites in response to short-term nutrient depletion and repletion. Day old chicks were offered a corn and soybean meal-based common starter diet from d1 to 14 that was formulated to meet all nutrient requirements of the birds. From d15 to 17, the experimental diets were offered, before returning all groups to a common diet from d18 to 20, at which point the experiment was terminated. A total of 5 experimental diets were designed. A standard grower diet served as a control and was offered to 1 of the 5 groups of chicks. The additional 4 experimental groups comprised diets that were low in digestible phosphorus (P), total calcium (Ca), crude protein and digestible amino acids (AA) or apparent metabolizable energy (AME). The common grower diet that was offered from d18-20 was designed to be nutritionally complete and was intended to explore dynamic response to nutrient repletion. Blood was drawn from 8 chicks per treatment at time 0 (immediately prior to introduction of the experimental diets) and then again 3, 6, 12, 24, and 48h after introduction of the nutrient depleted diets. Additionally, blood was drawn 3, 6, 12, 24, and 48h after the introduction of the nutritionally complete common grower diet. Chicks were not sampled more than once. Feed intake, body weight and feed conversion ratio (FCR) were assessed on d14, 17, and 20. Blood metabolites were analyzed using the iSTAT Alinity V handheld blood analyzer, the Vetscan VS2 Chemistry Analyzer and the iCheck Carotene Photometer. Live performance metrics were not affected by the short-term nutrient depletion and all chicks grew normally throughout the experiment. The diet with low digestible P generated a rapid temporary decrease in plasma P and an increase in plasma Ca, that were returned to baseline following the re-introduction of the common grower feed. Introduction of the diet with low total Ca resulted in a significant increase in plasma P, effects which were also mitigated during the nutrient repletion phase. Total plasma protein, albumin and uric acid (UA) were decreased, and plasma glucose increased, in the chicks that received the diet with low crude protein and digestible AA. There was a delayed increase in aspartate amino transaminase (AST) associated with the diets with low digestible P and low AME. These results demonstrate the capacity of blood biochemistry to adapt to quantitative and qualitative changes in nutrient intake. Point-of-care analysis of blood biomarkers offers nutritionists a valuable opportunity to calibrate nutritional matrices for common dietary ingredients, zootechnical feed additives and to optimize diet phase changes. It can be concluded that many blood biomarkers are plastic to changes in diet nutrient density and offer an objective index for optimization of nutritional programs for commercial broiler production.

259 Effect of very low calcium diet supplemented with microbial phytase in post-weaning piglets

Abstract Young piglets have an immature intestine that provides limited gastric acidity to digest nutrients compared with later stages of growth. Food has the intrinsic capacity to modify gastric acidity, particularly in relation to their concentrations of limestone, the ingredient with the greatest capacity to bind to acid. An experiment was conducted to evaluate the impacts of reducing dietary calcium (Ca) by reducing calcium supplementation immediately after weaning; compared with the recommendations of the NRC (2012), in association with phytase supplementation. The treatments were distributed during 3 phases [Phase 1 (P1, d 0-9), 2 (P2, d 10-16) and 3 (P3, d 17-35)]. Treatments were: 1) a diet low Ca that did not contained limestone during phase 1 (LowCa), P1 to P3 respectively, 0.51-0.60-0.65 % Ca and 0.48-0.43-0.38 % standardized ileal digestible P (STTD P), 2), diet 1 with microbial phytase (LowCa+PhytM); P1 to P3 respectively, 0.51-0.60-0.65 % Ca and 0.48-0.43-0.38% STTD P with 750 FTU phytase, and 3) a diet fulfilling requirement (NormalCa+PhytM) P1 to P3 respectively, 0.85-0.80-0.70 % Ca and 0.48-0.43-0.38 % STTD P with 750 FTU phytase. Piglets (n = 120) were allocated to 6 pens of 5 piglets per treatment in function of initial body weight (BW; 6.12 ± 0.028 kg). On d 0, 15 and 36, dual X-ray (DXA) bone densitometry was used to measure body fat, lean and mineral content (BMC) compositions using 8 piglets per treatment. At the end of phase 1 (d 9) a blood sample was collected. Data were analyzed using the SAS MIXED procedure with Tukey’s test to compare means. No differences were observed in growth performance or DXA measurements during the first phase. On d 9, LowCa piglets showed signs of hypocalcaemia with reduced plasma Ca (P = 0.03), increased plasma P (P = 0.02) and a lower Ca:P ratio in plasma (P = 0.04). From d 9-15, piglets that had received LowCa+PhytM showed greater average daily gain (ADG; P = 0.002) while other criteria did not differ between treatments. On d 15, the body composition evaluated by DXA showed no difference among dietary treatments. During phase 3, final BW and average daily feed intake were not modified by dietary treatments, while average daily gain and feed efficiency were greater in LowCa than in NormalCa+PhytM (+7.3 and 6.7%, respectively), and LowCa+PhytM was intermediate. Body composition on d 35 showed no difference among treatments while a tendency (P = 0.095) for greater BMC deposition (g/d) in LowCa in comparison with NormalCa+PhytM (+1.3 %). The implemented LowCa strategy resulted in momentary hypocalcemia which probably activated homeostatic mechanisms allowing piglets to be more efficient in using minerals and possibly other nutrients leading to better growth performance, without impact on bone mineralization.

Role of Leptin in Regulating Renal Phosphate Transport

Elevated plasma phosphate (Pi) levels, known as hyperphosphatemia, are associated with an increased risk of cardiovascular complications and mortality. Although studies have suggested a correlation between obesity and hyperphosphatemia/phosphate toxicity, the root cause of this observation has not been established. Since hyperleptinemia was also found to be associated with abnormalities in bone structure, we hypothesized that effects on renal Pi transport are responsible for this observation. To address this question, we studied hyperleptinemic mice (db/db, n=14) and compared them to wild-type mice (WT, n=10). Blood and urine samples, as well as kidney tissues, were collected and analyzed. Body weight was approximately twice as high in db/db compared to WT mice (59±3 vs. 30±2 g, P&lt;0.05). Plasma Pi levels in db/db mice were significantly greater (~1.5-fold) compared to WT mice (2.6±0.1 vs. 1.7±0.1 mmol/L, P&lt;0.05). However, urinary Pi /creatinine ratios were similar between genotypes. Plasma Ca2+ levels in db/db mice were significantly higher compared to WT mice (2.68±0.03 vs. 2.48±0.03 mmol/L, P&lt;0.05) alongside urinary Ca2+/creatinine ratios being significantly higher in db/db mice compared to WT mice (1.6±0.4 vs. 0.3±0.1 mmol/mmol, P&lt;0.05). Plasma parathyroid hormone (PTH, regulating Pi and Ca2+) levels were similar in both genotypes. The phosphaturic hormone fibroblast growth factor 23 (FGF23), which is produced and released from bone, was slightly but significantly elevated in db/db compared to WT mice (254±12 vs. 227±18 pg/mL, P&lt;0.05). Bone formation markers (osteocalcin and procollagen type I N-propeptide) and bone resorption markers (tartrate-resistant acid phosphatase 5b and C-terminal telopeptide of type I collagen) were similar between genotypes, indicating that Pi and Ca2+ release from bone may not be causing these mineral differences. To determine the role of the kidney for the development of hyperphosphatemia, we performed 32P radiotracer studies in acutely isolated renal brush border membrane vesicles. Sodium-dependent 32P transport was not significantly different between genotypes. To determine the ambient in vivo contribution of the Na+-Pi cotransporter Npt2a, we employed acute pharmacological inhibition with PF-06869206 (Npt2a inhibitor, 30 mg/kg b.w, n=7) or vehicle (n=11) and compared plasma Pi before and 2 hours after administration in db/db mice. Vehicle treatment slightly increased plasma Pi levels compared to baseline (2.6±0.1 vs. 2.1±0.1 mmol/L, P&lt;0.05); in contrast, the Npt2a inhibitor significantly reduced (~50%) plasma Pi levels compared to baseline (1.3±0.1 vs. 2.5±0.1 mmol/L, P&lt;0.05). In summary, our study demonstrates that hyperphosphatemia in db/db mice is not caused by changes in renal Pi transport or bone turnover, suggesting that possibly intestinal mechanisms are responsible for increased Pi, and possibly Ca2+, absorption. Of note, Npt2a inhibition was effective in reducing hyperphosphatemia in db/db mice, indicating a potential therapeutic strategy. This work was supported by a VA Merit Review Award IBX004968A (to Dr. Rieg) and a Pilot Project from the USF Microbiomes Institute (to T.R. and J.D.R). 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.

Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study

Background and aimDiabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. MethodsA hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman’s rank correlation was used to evaluate the relationship between the categorical variables. ResultsThe median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= −0.486, p<0.001). ConclusionPlasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.

ATP-dependent ion-transport systems functioning in immunocompetent cells of men with erectile dysfunction due to combat trauma

Background. The study of the problem of physical and mental health of people who have survived combat trauma is a component of a wide field of research on the problem of stress, which manifests itself at all levels of the organization of the body. Combat injuries, in particular those of the areas of pelvis and genitourinary system, stressful events, lead to the development of erectile dysfunction (ED). In recent decades, a sufficient number of scientific facts have been accumulated, which confirm the significant influence of stress factors on the reduction of sexual desire and sexual activity. Therefore, determination of Ca2+,Mg2+- and Na+,K+-ATPase activity on a convenient model like peripheral blood lymphocytes add complexity to the understanding of the development of the pathophysiological and pathobiochemical mechanisms of the body, the result of which is the development of ED. Materials and methods. The research was conducted on peripheral blood lymphocytes of men injured as a result of combat operations (shrapnel and bullet wounds) in the Russian-Ukrainian war and treated at the Military Medical Clinical Center of the Western Region. The research group of men with combat injuries was divided into two subgroups: men aged 20–39 years (subgroup 1) and men aged 40–53 years (subgroup 2). The control group consisted of 48 practically healthy men without complaints of sexual dysfunction or cardiac, neurological or endocrinological pathology. Among the men of the control group were 30 men aged 20–39 years (subgroup 3) and 18 men aged 40–53 years (subgroup 4). Results. It has been shown that in the peripheral blood lymphocytes of men injured as a result of hostilities, there is a decrease in Na+,K+-ATPase activity and Ca2+,Mg2+-ATPase activity of the plasma membrane and endoplasmic reticulum, which leads to overloading of the cytosol with Na+ and Ca2+ ions, respectively, which is characteristic of pathological processes. Conclusion. Erectile dysfunction due to combat trauma is accompanied by a decrease in both Ca2+,Mg2+-ATPase activity of the plasma membrane and Ca2+,Mg2+-ATPase activity of endoplasmic reticulum of blood lymphocytes. As the age of patients with disorders of sexual function increases, the decrease in Ca2+,Mg2+-ATPase activities becomes more expressed. In men with erectile dysfunction due to combat trauma, the activity of Na+,K+-ATPase is also inhibited. According to the ROC curve, Ca2+,Mg2+-ATPase activity of the endoplasmic reticulum in blood lymphocytes is a potential biomarker of erectile dysfunction.

The influence of sunflower oil in meals on the blood mineral profile of dairy cows

Minerals are essential substances with an important function in livestock, and their disbalance negatively affects the health and production, especially of ruminants. The addition of fat to the rations of dairy cows impacts the overall and mineral metabolism, and thus on health and production. The aim of the research was to examine the correlative relationships between balanced production meals and the mineral status of lactating cows with different ration compositions with or without the presence of vegetable oil. The research was conducted on 30 dairy cows of the Holstein breed at the Butmir farm, Sarajevo, Bosnia and Herzegovina. Three groups of 10 animals were formed based on productivity (A, 13-15 kg of milk/day, B, 19-21 kg of milk/day and C, 25-27 kg of milk/day). Samples of feed, blood plasma and milk of animals were collected on three occasions a 3-week intervals. According to the feed analysis results, the rations were standardized for each group, given for three weeks without oil,and then for three weeks with the addition of sunflower oil in the amount of 2.5% of the ration dry matter. After determining the content of basic nutrients, dry matter and ash in the rations, the concentrations of Ca, Mg, Na and K were determined by atomic absorption spectrophotometry,while the colorimetric method was used to analyse P according to Woy and Eggertz-Finkener. Analysis of blood mineral parameters was performed spectrophotometrically. The content of fat, proteins, lactose, and non-fat dry matter in milk samples was determined by infrared spectrometry using an automatic analyser. Based on the results, we observed a similarity in changes of values and the statistical significance of the differences in plasma Ca, P and Mg between the study groups and at sampling intervals. Milk production was positively correlated with the concentration of Mg and Ca with addition of the sunflower oil to the meal, while no correlation coefficient was established for P in any of the samplings. Balanced meals with and without the addition of oil did not significantly affect the content of Ca, P or Mg in the blood plasma of the tested animals, nor were significant differences found between the groups. However, by determining the correlations between milk parameters and blood biochemical parameters, a significant positive correlation was established between the amount of milk and Ca and Mg levels with a diet supplemented by oil. Given that the addition of sunflower oil in the amount of 2.5% of dry matter of the balanced rations for cows had no negative effects on the mineral profile and the parameters of the tested animals, we conclude that the introduction of this oil could be useful both from the economic point and improving nutritional composition of milk as an animal food present in the daily human diet.

Associations between plasma metal elements and risk of cognitive impairment among Chinese older adults.

The relationship between plasma metal elements and cognitive function is unclear, especially in extremely older individuals. This present study aimed to explore the association between plasma metal concentrations and the risk of cognitive impairment (CI) in Chinese extremely older adults. Individuals aged ≥90 years with plasm metal concentration data from the fifth wave of the 2008 Chinese Longitudinal Healthy Longevity Survey were included. Plasma selenium (Se), manganese (Mn), magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), and zinc (Zn) concentrations were measured using inductively coupled plasma optical emission spectroscopy. Cognitive function was assessed by the Chinese version of the mini-mental state examination. The study enrolled 408 participants. Participants with CI had significantly lower plasma Se, Mn, and Fe levels and higher Ca levels than those with normal cognitive function (p < 0.05). Plasma Se, Mn, Ca, and Fe concentrations were significantly associated with CI risk in both single- and multiple-element logistic regression models. Additionally, the multiple-element model results showed that the adjusted odds ratios for CI were 0.042 (95% confidence interval 0.016-0.109), 0.106 (0.044-0.255), 7.629 (3.211-18.124) and 0.092 (0.036-0.233) for the highest quartiles compared to the lowest quartiles of Se, Mn, Ca, and Fe, respectively. Moreover, subgroup analyses by age, sex, and body mass index suggested a consistent significant correlation (p < 0.05). Therefore, decreased plasma Se, Mn, and Fe and increased plasma Ca levels were associated with CI risk in Chinese older adults. These findings are of great significance for the development of programs to delay cognitive decline in the elderly.

Impact of deoxynivalenol in a calcium depletion and repletion nutritional strategy in piglets.

This study evaluated the effect of dietary calcium (Ca) levels and deoxynivalenol (DON) contamination on Ca and phosphorus (P) utilization and bone mineralization in piglets. During an initial 13-d depletion phase, 64 piglets (15.7 ± 0.7kg) received a control (DON-) or DON-contaminated treatment (DON+, 2.7mg DON/kg) with either a low Ca (Ca-, 0.39%) or normal Ca level (Ca+, 0.65%) with a constant digestible P level (0.40%). A second group of 16 piglets received DON- or DON+ treatments for 9 d for gene expression analysis. During the subsequent 14-d repletion phase, all piglets were fed a Ca+ DON- diet containing 0.65% Ca and 0.35% digestible P without DON. After 5 d of the depletion phase, the absorption of P (DON × Ca; P < 0.05) and Ca was increased by the Ca- (P < 0.01) and DON+ (P < 0.01) diet. After 13 d, feed conversion ratio (P < 0.01) and average daily feed intake (P = 0.06) tended to decrease with the Ca- diet. The bone mineral content (BMC) gain was decreased by Ca, especially with Ca- DON + (DON × Ca, P < 0.05). The P absorption was increased by Ca- DON + (DON × Ca, P < 0.01), although the P retention efficiency was only increased by Ca+ DON + (DON × Ca, P < 0.001). The absorption of Ca was increased by DON+ (P < 0.001), and the Ca efficiency was increased by Ca- DON- (DON × Ca, P < 0.01). After 9 d, the gene expression of intestinal claudin 12 (P < 0.01) and CYP24A1 (P < 0.05), femur cortical RANKL (P < 0.05) and OPG (P = 0.06), and renal calbindin D9K (P < 0.05) and Klotho (P = 0.07) were decreased by DON+. The Ca (P = 0.06) and magnesium (P < 0.01) concentrations were decreased by DON+, and the Ca (P = 0.06) and P digestibility (P < 0.01) were increased. After the repletion phase, Ca- piglets recovered their BMC deficit, but not those receiving DON+ (DON × Ca; P = 0.06). The Ca (P < 0.05) and P (P = 0.06) retention efficiency tended to increase with Ca-. The absorption of Ca and P was increased by Ca- and DON+ (DON × Ca, P < 0.05). The results show that piglets increased their Ca and P utilization efficiency, allowing them to recover the BMC deficit caused by Ca-, but not when the piglets were exposed to DON. Pigs previously receiving Ca-deficient diet with DON still have lower body Ca and P, leading to elevated calcitriol concentrations and enhanced Ca and P intestinal absorption. The fact that DON decreased the expression of genes implicated in Ca intestinal and renal transport and P excretion after 9 d can potentially explain the reduced plasma Ca concentration.

Activation of Hepatic Branched-Chain α-Ketoacid Dehydrogenase Complex by Vitamin D Deficiency in Rats.

Branched-chain α-ketoacid dehydrogenase (BCKDH) complex is a rate-limiting enzyme in branched-chain amino acid catabolism and is subject to inactivation via phosphorylation by BCKDH kinase (BDK). In the present study, we examined the effects of vitamin D-deficiency on hepatic BCKDH and BDK activities in rats. Rats fed a vitamin D-deficient diet long-term showed a slight but significant decrease in plasma Ca concentration, which was associated with an elevation of BCKDH activity and a decrease in BDK activity. These results suggest that vitamin D deficiency promotes BCAA catabolism via BCKDH activation, which resulted from BDK suppression. It is proposed that Ca2+-dependent BDK inhibition by thiamine pyrophosphate may be involved in the BDK suppression.

DISTILLER’S DRIED GRAINS SUPPLEMENTED Wz3ITH ENZYME COCKTAIL AND YEAST AFFECT EGG QUALITY, REPRODUCTIVE PERFORMANCE AND BLOOD PROFILE OF BREEDING HENS

This experiment aimed to examine the influences of distiller’s dried grains with solubles (DDGS) in breeding hen’s nutrition (0, 10, and 20%, respectively) with or without enzyme cocktail blend and yeast (Saccharomyces cerevisiae, SC) supplementation on the sustainability of eggs and semen quality, fertility and hatchability, and blood biochemistry. In total, 360, twenty weeks old indigenous Inshas breeding hens and 36 Inshas cocks (for natural mating) were used in the experiment. Inshas is a crossing breed that originated from mating Sinai and White Plymouth Rock breeds. Hens and cocks of all experimental groups had approximately similar initial body weights (1,560 ± 12.3 g) at the start of the experiment and were divided into 12 groups, each containing three replicates (10 hens + 1 cock). Moreover, 60 cocks were divided into 12 groups of five cocks each and housed individually in cages for semen quality estimation using the artificial collection technique. Increasing DDGS up to 20% in diets of breeding hens decreased (p≤0.05) eggshell thickness compared to 0 and 10% DDGS, but it elevated (p≤0.05) color of yolk and Haugh unit score during the storage period. Dietary treatments did not significantly affect the percentage fertility, hatchability, and abnormality of embryos and body weight of day-old chicks. Semen quality was not significantly affected by dietary DDGS. Yeast supplementation increased (p≤0.05) sperm concentration per ejaculate by 5.21% and total normal sperm/ejaculate and sperm concentration by 5.87%. Increasing DDGS levels up to 10% and 20% decreased blood plasma total cholesterol by about 4.1%. Enzyme cocktail supplementation increased (p≤0.05) blood plasma Ca by 5.4% of 20% DDGS diets, but other blood plasma parameters were unaffected. Enzyme cocktail addition to DDGS diets also decreased plasma cholesterol by 3.63%. Feeding a 10% and 20% DDGS diet increased (p≤0.05) plasma creatinine by 9.75% and decreased the uric acid/creatinine ratio by about 11.1%. In conclusion, corn DDGS could be included in dual-purpose breeding hen’s diet up to 20% without adverse effects on the sustainability of the quality of eggs and semen, fertility and hatchability, and blood biochemistry. Furthermore, enzyme cocktail at 500 gm/ton feed and yeast at 1 kg/ton feed supplementations significantly and similarly improved eggshell thickness by 1.44-1.72%, and yeast increased sperm concentration and total sperm output per ejaculate. Key words: Distillers dried grains with soluble; Breeding hens; Multi-enzymes; Yeast; Fertility; Hatchability; Semen quality.