TCA Concentrations Research Articles

Effects of injectable calcitriol on mineral metabolism and postpartum health and performance in dairy cows

Objectives were to determine the effects of an injectable formulation of calcitriol on Ca concentration, risk of clinical diseases, and performance in dairy cows. Cows were blocked by lactation number (1 vs. >1) and calving sequence and, within block, assigned randomly within 6 h of calving to receive subcutaneously vehicle only (CON, n = 450) or 200 (CAL200, n = 450) or 300 μg of 1α,25-dihydroxyvitamin D3 (CAL300, n = 450). Cows were fed the same acidogenic diet prepartum. Blood was sampled before treatment administration and again during the first 11 d postpartum and analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), Mg (tMg), and P (tP), β-hydroxybutyrate, carboxylated osteocalcin (cOC), and undercarboxylated osteocalcin (uOC). Cows were evaluated for diseases in the first 60 d postpartum. Reproduction and survival were monitored for the first 300 d postpartum. Calcitriol increased concentration of blood iCa (CON = 1.12 vs. CAL200 = 1.23 vs. CAL300 = 1.27 mM), plasma tCa (CON = 2.29 vs. CAL200 = 2.44 vs. CAL300 = 2.46 mM), and plasma tP (CON = 1.72 vs. CAL200 = 2.21 vs. CAL300 = 2.28 mM), and differences were observed during the first 5 d postpartum for iCa and tCa, and the first 7 d postpartum for tP. Concentrations of tMg were lower in calcitriol-treated cows than in CON cows (CON = 0.81 vs. CAL200 = 0.78 vs. CAL300 = 0.75 mM), and differences were observed during the first 5 d postpartum. Calcitriol increased plasma concentrations of cOC (CON = 14.5 vs. CAL200 = 23.0 vs. CAL300 = 19.8 ng/mL) and uOC (CON = 1.6 vs. CAL200 = 3.4 vs. CAL300 = 2.6 ng/mL). Prevalence of subclinical hypocalcemia was less in calcitriol-treated cows (CON = 19.0 vs. CAL200 = 4.7 vs. CAL300 = 9.3%); however, benefits on health were only observed in overconditioned cows (n = 270/1,350). Calcitriol reduced incidence of retained placenta (CON = 14.3 vs. CAL200 = 5.1 vs. CAL300 = 5.9%), puerperal metritis (CON = 12.7 vs. CAL200 = 6.1 vs. CAL300 = 2.5%), and morbidity (CON = 72.1 vs. CAL200 = 57.4 vs. CAL300 = 56.9%) in cows with BCS greater than 3.50, but no benefit on health was observed in cows with BCS equal to or less than 3.50 at parturition. Milk yield did not differ among treatments. Pregnancy at first AI did not differ, but pregnancy rate after the first AI was slower for calcitriol-treated cows because of reduced insemination rate and pregnancy per AI. We found that CAL200 reduced death but increased culling in cows without calving problems. Collectively, results indicate that treatment with calcitriol at parturition was effective in improving concentrations of iCa, tCa, and tP, which reduced the risk of hypocalcemia. Pregnancy rate was reduced by calcitriol treatment, and benefits on health performance were limited to overconditioned cows. Thus, treatment of all cows is not supported, and proper identification of cohorts of cows that benefit from postpartum interventions that increase blood calcitriol or calcium is needed.

Inflammatory diseases in dairy cows: Risk factors and associations with pregnancy after embryo transfer

The objectives of the present prospective cohort study were to identify risk factors for inflammatory diseases in Holstein-Gyr crossbred dairy cows and characterize the associations of those diseases with pregnancy per embryo transfer (ET). Diseases were diagnosed in the first 60 d postpartum in 252 primiparous and 481 multiparous cows. Uterine diseases (UTD) included retained placenta, metritis, clinical endometritis, and subclinical endometritis. Nonuterine diseases (NUTD) included mastitis, lameness, pneumonia, and displaced abomasum. Blood was sampled on d 0, 1, and 2 postpartum and analyzed for concentrations of haptoglobin, fatty acids, total Ca (tCa), P, and Mg, and again on d 8 postpartum and analyzed for concentration of β-hydroxybutyrate. The association between concentrations of metabolites in serum and inflammatory diseases was determined. Cows received a timed ET program starting 28 ± 3 d postpartum with first ET at 46 ± 3 d postpartum using fresh in vitro-produced embryos. Pregnancy was diagnosed on d 31 and 59 of presumptive gestation. Overall, 63.3% of the cows were diagnosed with UTD and 20.6% with NUTD. The risk factors for UTD included season of calving, parity group, calving problems, days with subclinical hypocalcemia, and serum concentrations of haptoglobin and Mg, whereas the risk factors for NUTD were parity group and serum Mg concentration. Cows that developed UTD had increased concentrations of haptoglobin on d 2 and fatty acids on d 1 and 2, and reduced concentrations of tCa on d 1 and 2 and of P and Mg on d 2 postpartum compared with cows without UTD. Cows that developed NUTD had increased concentrations of fatty acids on d 0 to 2 postpartum, and decreased concentrations of tCa and P on d 0 and 1, and of Mg on d 1 and 2 postpartum compared with cows without NUTD. Cows that developed NUTD had a 340-kg reduction in milk yield in the first 60 d postpartum. Inflammatory diseases were associated with lesser body condition score and increased loss of body condition in the first 70 d postpartum. Maintenance of pregnancy after ET was reduced in UTD cows following the first (41.7 vs. 25.4%) or all ET (46.4 vs. 36.2%), whereas maintenance of pregnancy was reduced in NUTD cows only at the second ET (39.0 vs 25.9%). The reduced pregnancy maintenance in UTD cows combined with a reduced 21-d service rate (61.9 vs. 54.8%) decreased the 21-d cycle pregnancy rate (28.6 vs. 19.9%) and the hazard of pregnancy to 300 d postpartum by 35%, resulting in an extra 32 d open. In conclusion, inflammatory diseases depressed fertility in dairy cows receiving ET, with the greatest impact observed in UTD cows. This suggests that local inflammation of the uterus impairs maintenance of pregnancy in dairy cows following ET.

Blood calcium as a prognostic indicator of left-displaced abomasum postsurgical correction success

Subclinical hypocalcemia, a reduction in blood calcium concentrations without apparent clinical signs of milk fever, occurs in 25 to 50% of early-postpartum dairy cows. Compared to their normocalcemic counterparts, research has shown these cows are at an increased risk of additional early-lactation diseases, including left-displaced abomasum (LDA). However, no work has assessed the association of total calcium (tCa) concentration at the time of LDA correction on subsequent milk yield and survival within the herd. Pending future development of an economical and accurate on-farm test for hypocalcemia, the ability to assess LDA prognosis post-surgical correction based on pre-correction blood tCa concentration is of great interest to practitioners. Therefore, our objective was to determine the association of blood tCa concentration at the time of LDA surgical correction on milk yield and removal from herd in the 60 d post-correction.

Absence of Bsep/Abcb11 attenuates MCD diet-induced hepatic steatosis but aggravates inflammation in mice.

BackgroundBile acids (BAs) regulate hepatic lipid metabolism and inflammation. Bile salt export pump (BSEP) KO mice are metabolically preconditioned with a hydrophilic BA composition protecting them from cholestasis. We hypothesize that changes in hepatic BA profile and subsequent changes in BA signalling may critically determine the susceptibility to steatohepatitis.MethodsWild‐type (WT) and BSEP KO mice were challenged with methionine choline‐deficient (MCD) diet to induce steatohepatitis. Serum biochemistry, lipid profiling as well as intestinal lipid absorption were assessed. Markers of inflammation, fibrosis, lipid and BA metabolism were analysed. Hepatic and faecal BA profile as well as serum levels of the BA synthesis intermediate 7‐hydroxy‐4‐cholesten‐3‐one (C4) were also investigated.ResultsBile salt export pump KO MCD‐fed mice developed less steatosis but more inflammation than WT mice. Intestinal neutral lipid levels were reduced in BSEP KO mice at baseline and under MCD conditions. Faecal non‐esterified fatty acid concentrations at baseline and under MCD diet were markedly elevated in BSEP KO compared to WT mice. Serum liver enzymes and hepatic expression of inflammatory markers were increased in MCD‐fed BSEP KO animals. PPARα protein levels were reduced in BSEP KO mice. Accordingly, PPARα downstream targets Fabp1 and Fatp5 were repressed, while NFκB subunits were increased in MCD‐fed BSEP KO mice. Farnesoid X receptor (FXR) protein levels were reduced in MCD‐fed BSEP KO vs WT mice. Hepatic BA profile revealed elevated levels of TβMCA, exerting FXR antagonistic action, while concentrations of TCA (FXR agonistic function) were reduced.ConclusionPresence of hydroxylated BAs result in increased faecal FA excretion and reduced hepatic lipid accumulation. This aggravates development of MCD diet‐induced hepatitis potentially by decreasing FXR and PPARα signalling.

Peripartum Ca and P homeostasis in multiparous sows fed adequate or excess dietary Ca

The recent increased prevalence of uterine prolapses in sows around parturition has led to inferences that the prolapses may be associated with hypocalcemia. However, limited data are available to support that hypocalcemia occurs in sows. Hypocalcemia in dairy cows is associated with feeding excess dietary Ca during late gestation. The excess Ca is assumed to suppress homeostatic mechanisms critical to maintain serum Ca concentrations as the Ca demand increases during the early stages of lactation. In this experiment, sows were fed diets with excess Ca during late gestation and early lactation to assess the potential development of hypocalcemia in the peripartum period. Twelve crossbred (Large White × Landrace) multiparous gestating sows were fed a control diet (CON), 0.65% Ca to 0.38% standardized total tract digestible P (STTD P) and 0.67% Ca to 0.38% STTD P in gestation and lactation diets, respectively) or a high Ca diet (HCa, 1.75% Ca to 0.46% STTD P and 1.75% Ca to 0.45% STTD P in gestation and lactation diets, respectively). The diets were fed from gestation day 86 þ ± 1 until the end of lactation (27 þ ± 2 days period). On day 112 of gestation, indwelling venous catheters were placed in each sow. Blood samples were collected at 15-min intervals within four designated times (0700, 1000, 1300 and 1700 h) on gestation day 113 and lactation days 1, 3 and 5. Venous blood pH, gases (pO2, pCO2 and HCO3−), electrolytes (K+, Na+ and Cl−), ionized Ca (iCa), metabolites (glucose and lactate), plasma total Ca (tCa), and P were analyzed. Overall, sows fed HCa diet had greater (P < 0.001) concentrations of blood iCa and plasma tCa than sows fed CON diets. No clinical signs of Ca metabolism disorders were observed. Unexpectedly, concentrations of plasma P in sows fed HCa diets were lower (P < 0.001) than in sows fed CON diets. Plasma P tended to decrease (P = 0.057) as day of lactation increased. Differences between dietary treatments for blood pH, gases, electrolytes and metabolites were not detected (P > 0.05). No evidence for hypocalcemia was detected in peripartum sows fed CON or HCa diets. These data imply that excess Ca in late gestation diets did not result in hypocalcemia during the peripartum period. Future experiments should focus on factors other than hypocalcemia to identify causes of uterine prolapses in sows.

A Review Article on Selective Serotonin Reuptake Inhibitors (SSRIS)

Depression, tension and mental health have been ignored as a serious issue since ages. Depression can be fatal or life-threatening, if not treated to this problem. Antidepressants are also regularly used to treat many other conditions, such as social phobia, fibromyalgia, panic disorder, anxiety/anxiety depression, PTSD, OCD, PMDD, and menopause. The major antidepressant used in the study followed oral prescribing trends. A “serious adverse reaction means an adverse reaction which is fatal, life-threatening, disabling, incapacitating, or which results in or prolongs hospitalization.” Material method collect from Google, Wikipedia, Elsevier, PubMed, Google scholar, Sci-Hub etc. This is a meta-analysis study. Fluoxetine have the longest half-life, but Fluvoxamine have short half-life. SSRIs increase the serum concentrations of the latter two drugs, potentiating their effects and increasing the risk of toxicity. Fluoxetine and Paroxetine specifically, are known to cause a 5-fold increase in serum TCA concentration upon co-administration. By in the addition of combination therapy SSRIs associated many types of adverse drug reaction and some time it can cause serotonin syndrome also.&#x0D;

Technical note: Effect of storage time and temperature on total calcium concentrations in bovine blood

Our objectives were to examine the stability of (1) serum and plasma total calcium (tCa) after delayed separation of bovine whole blood stored at 4°C, and (2) frozen serum and plasma tCa stored at -80°C. Whole blood was collected from 19 cows into vacutainer tubes (Becton Dickinson, Franklin Lakes, NJ) containing no additives (serum) or lithium heparin (plasma). Baseline tCa concentrations (0-h tCa) were determined on serum and plasma harvested within 2 h of blood collection. To evaluate the effect of prolonged whole blood storage at 4°C, serum and plasma were harvested from samples after 6, 24, 48, 72 h, and 7 and 14 d of storage. For evaluation of the stability of frozen serum and plasma stored at -80°C, samples were stored for 7 d and 1, 3, 6, and 12 mo. The median 0-h tCa concentration for serum and plasma was 2.25 mmol/L (range: 1.58 to 2.60 mmol/L) and 2.28 mmol/L (range: 1.60 to 2.65 mmol/L), respectively. The average difference in tCa from 0-h samples ranged from -0.02 to 0.03 mmol/L for all samples stored at either 4 or -80°C. The median within-cow variability for whole blood samples stored at 4°C was 1.1 and 1.0% for serum and plasma, respectively, and for serum and plasma stored at -80°C was 1.1 and 1.3%, respectively. When whole blood was stored at 4°C, no differences in serum or plasma tCa concentrations were observed across the evaluated time points as compared with 0-h concentrations. Similarly, frozen serum and plasma stored at -80°C remained stable up to 12 mo. Therefore, our findings show that whole blood samples may be stored for at least 14 d at 4°C in vacutainer tubes containing no additives or lithium heparin without biologically important changes in tCa concentrations beyond expected analytical variation. Additionally, serum or plasma may be stored at -80°C for up to 12 mo with no effect on tCa concentrations.

Determination of a serum total calcium concentration threshold for accurate prediction of ionized hypercalcemia in dogs with and without hyperphosphatemia.

BackgroundTotal serum calcium (tCa) concentrations are poorly predictive of ionized calcium (iCa) status in dogs.HypothesisThere is an optimal threshold of tCa concentration that is highly predictive of ionized hypercalcemia and this threshold is higher in hyperphosphatemic dogs as compared to nonhyperphosphatemic dogs.AnimalsNonhyperphosphatemic (n = 1593) and hyperphosphatemic (n = 250) adult dogs.MethodsRetrospective medical record review of paired tCa and iCa concentration measurements in dogs presented to a university teaching hospital over a 5‐year period. Positive and negative predictive values, sensitivity, and specificity were calculated for tCa concentration thresholds of 11.0‐15.0 mg/dL (upper limit of laboratory reference interval = 11.5 mg/dL) in nonhyperphosphatemic and hyperphosphatemic groups.ResultsIn nonhyperphosphatemic dogs, an optimal tCa concentration threshold of 12.0 mg/dL resulted in a positive predictive value of 93% (95% confidence interval [CI], 84%‐98%) and sensitivity of 52% (95% CI, 43%‐61%) for ionized hypercalcemia. An optimal tCa concentration threshold was not identified for hyperphosphatemic dogs. The nonhyperphosphatemic dogs had a higher prevalence of ionized hypercalcemia than the hyperphosphatemic dogs (7 versus 3%, P = .04) and a lower prevalence of ionized hypocalcemia (23 versus 62%, respectively; P < .001).Conclusions and Clinical ImportanceHigh tCa concentrations are strongly predictive of ionized hypercalcemia in nonhyperphosphatemic adult dogs and should prompt further diagnostic testing to determine the underlying cause of hypercalcemia. In this population, dogs without increased tCa concentrations rarely had ionized hypercalcemia, but iCa concentrations still should be evaluated in patients with tCa concentrations within the reference interval if there is clinical suspicion for calcium abnormalities.

Effect of storage time and temperature on total calcium concentrations in bovine blood

Subclinical hypocalcemia (SCH), a reduction in blood calcium concentrations without apparent clinical signs of milk fever, occurs in 25 to 50 % of early-postpartum dairy cows. Compared to their normocalcemic counterparts, these cows have an increased risk of subsequent disease developments, reduced milk production, and poorer reproductive performance. Due to the absence of an economical and accurate on-farm test, the mainstay of individual cow testing and herd-level monitoring is done through total calcium (tCa) analysis performed at regional laboratories or veterinary clinics. Due to practicality reasons, this often results refrigeration of whole blood for various lengths of time prior to centrifugation or prolonged storage of frozen plasma or serum. In order to provide bovine practitioners and researchers with the optimal method of handling samples for tCa testing, our objective was to examine the effect of storage time and temperature on tCa concentrations in bovine blood.

Safety evaluation of Terminalia catappaLinn (Combretaceae) aqueous leaf extract: Sub-acute cardio-toxicopathological studies in albino Wistar rats

This study evaluated the safety of sub-acute administration of Terminalia catappa L. aqueous leaf extract (TCA) on cardiac biochemical parameters. Graded concentrations (200, 400 and 800 mg/kg) of TCA wereorally administered daily for 28 days. Cardiac biochemical parameters of toxicity were thereafter accessedusing standard methods forsuperoxide dismutase, peroxidase, glutathione-S-transferase, reduced glutathione, lipid peroxidation, protein levels, cholesterol, triglyceride, lactate dehydrogenase and creatinine kinase. TCA treatment did not alter the heart weight and cardiac biochemical parameters. Nonetheless, at 800 mg/kg, the antioxidant profile was significantly improved after TCA treatment. There was no mediated sign of treatment toxicityas well asa change in cardiac histological architecture. T. catappaaqueous leaf extract is relatively non-toxic to the heart at the experimental doses and also within the test period.

Intravenous calcium infusion in a calving protocol disrupts calcium homeostasis compared with an oral calcium supplement

Hypocalcemia is a common postpartum condition in dairy cows, which negatively affects health and production. Intravenous Ca infusions are commonly included in calving protocols to prevent or mitigate the effect of hypocalcemia in multiparous cows. Thus, we sought to contrast the effect of intravenous Ca infusion against voluntary oral Ca intake on Ca metabolism. Serum total Ca (tCa) and whole-blood ionized Ca (iCa) were monitored in 24 multiparous Holstein cows after parturition. Precalving diets were formulated with a positive dietary cation-anion difference of 172 mEq/kg of DM and contained 4.1 g of Ca/kg of DM. At parturition, cows were blocked by calving sequence and calcemic status as either normocalcemic (cutoff threshold of iCa ≥1.10 mmol/L) or hypocalcemic (cutoff threshold of iCa <1.10 mmol/L). Cows in each block were randomly assigned to 1 of 2 treatments: either an oral source of Ca (Ca-Oral; n = 12) or an intravenous source of Ca (Ca-IV; n = 12). Cows in the Ca-Oral group were offered a 20-L commercial Ca suspension (48 g of Ca) for voluntary consumption. The supplement contained Ca carbonate, Ca formate, Ca propionate, and other minerals and vitamins (Farm-O-San Reviva, Trouw Nutrition, Amersfoort, the Netherlands). Cows in the Ca-IV group received a 450-mL intravenous Ca solution (13 g of Ca) that contained 298 mg/mL of Ca gluconate, 33 mg/mL of magnesium chloride, and 82 mg/mL of boric acid (AmosCAL, Kommer-Biopharm BV, Heiloo, the Netherlands). Both treatments were initiated within 25 ± 10 min after calving. The oral Ca suspension was offered to cows in a 25-L bucket and was available for 10 min. All cows in the Ca-Oral group voluntarily consumed the entire 20 L of the Ca suspension within 5 min. Blood samples for Ca analyses were collected at 0 (before treatment initiation), 1, 3, 10, and 18 h relative to treatment, and at 0700 and 1900 h for the next 2 consecutive days, to represent the 24-, 36-, 48-, and 60-h sampling time points. In Ca-IV cows, both iCa and tCa concentrations peaked at 1 h (1.54 mmol/L for iCa and 2.85 mmol/L for tCa) and declined to a nadir at 24 h following treatment initiation (0.94 mmol/L for iCa and 1.74 mmol/L for tCa). Although whole-blood iCa and serum tCa were higher at 1 and 3 h in Ca-IV cows, concentrations of iCa were greater for Ca-Oral cows at 18, 24, and 36 h and for tCa at 24 and 36 h. Our data indicate that intravenous Ca infusion immediately induced a state of hypercalcemia followed by lower whole-blood iCa and serum tCa concentrations 24 h later compared with oral Ca.

Relationships among electrolyzed water postharvest treatments on winegrapes and chloroanisoles occurrence in wine

Electrolyzed water (EW) has attracted much recent attention as a high-performance, new technology for its potential use in the food industry. However, the risk of postharvest EW treatments of winegrapes destined for winemaking is the chloroanisoles formation in the final product. In the present study, we investigated the impact of postharvest grape EW and storage treatments on the occurrence of these compounds in wine, 2,4,6-trichloroanisole (TCA) being the main compound responsible for the cork taint off-flavor due to its extremely low perception threshold. The results revealed that the presence of TCA in the wines depended on the concentration of residual free chlorine in the must from the EW treatment. Particularly, TCA was not detected in wine when active chlorine concentrations higher than 0.005 mg/L were present in the must. Chloroanisole and chlorophenol levels in wine were strongly affected not only by EW but also by grape storage conditions (temperature, time, sunlight exposition). The results showed that the 24-hours grape storage at a controlled temperature of 20 °C in the dark, after EW treatment, resulted in the highest TCA concentrations in wines (7.3 ± 2.7 ng/L), while storage and withering in sunlight seemed to mitigate its presence in wine. This could suggest that microbiological formation of chloroanisoles may have been influenced by the storage temperature and germicidal effect of UV light. Biochemical mechanism of chloroanisoles production in grapes and wine is unknown, but the combination of residual free chlorine on the grape surface and the controlled storage conditions in the dark may have positively influenced the bio-formation of chloroanisoles and therefore their presence in wine.

UV-light and dietary vitamin D and their effects on ionized calcium and 25-OH-D plasma concentrations in captive gentoo penguins (Pygoscelis papua).

In this study, the effect of ultraviolet (UV) light and dietary vitamin D on calcium metabolism in permanently indoor-housed gentoo penguins (Pygoscelis papua) was investigated. The study consisted of three periods, each completed with blood samples to analyse plasma concentrations of 25-OH-D, 1,25-(OH)2 -D, ionized (iCa) and total calcium (tCa). During the first study period (D), animals were housed under routine conditions without UV-light and fed a diet of different fish species, supplemented with 1,000IU vitamin D per animal and day. The following study period (Baseline) of 28-day duration consisted of the same diet without any vitamin D supplementation and without UV-light. During the study period (UVB) artificial UV-light was added for 3weeks. The vitamin D content of fish was measured by high-performance liquid chromatography. It varied between fish species and between facilities, ranging from no measurable content in capelin (Mallotus villosus) to 7,340IU vitamin D/kg original matter (OM) in herring (Clupea spp). The average dietary vitamin D content was 311IU/kg OM at facility 1 and 6,325IU/kg OM at facility 2, resulting in a vitamin D intake per animal and day without supplementation of 130IU (25.5IU/kg body weight BW) and 2,454IU (438.2IU/kg BW) respectively. The supplementation of vitamin D elevated significantly the plasma concentrations of 25-OH-D by an intraindividual difference of 15 (range -2 to 59)nmol/L and tCa by 0.1 (0.0-0.3) mmol/L only at facility 2. The exposure to UV-light raised the blood concentrations of tCa at facility 2 by 0.15 (0.1-0.2) mmol/L, and of iCa and tCa for females at facility 1 by 0.23 (0.13-0.41) mmol/L and 1.8 (1.1-2.5) mmol/L respectively. No significant influence of the study periods (D) and (UVB) was found for the concentrations of 1,25-(OH)2 -D at both facilities.

Effects of prepartum dietary cation-anion difference and source of vitamin D in dairy cows: Vitamin D, mineral, and bone metabolism

Pregnant Holstein cows, 28 nulliparous and 51 parous, were blocked by parity and milk yield and randomly allocated to receive diets that differed in dietary cation-anion difference (DCAD), +130 or -130 mEq/kg, and supplemented with either calcidiol or cholecalciferol at 3 mg/11 kg of dry matter from 255 d of gestation until parturition. Blood was sampled thrice weekly prepartum, and on d 0, 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, and 30 postpartum to evaluate effects of the diets on vitamin D, mineral and bone metabolism, and acid-base status. Blood pH and concentrations of minerals, vitamin D metabolites, and bone-related hormones were determined, as were mineral concentrations and losses in urine and colostrum. Supplementing with calcidiol increased plasma concentrations of 25-hydroxyvitamin D3, 3-epi 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 compared with supplementing with cholecalciferol. Cows fed the diet with negative DCAD had lesser concentrations of vitamin D metabolites before and after calving than cows fed the diet with positive DCAD, except for 25-hydroxyvitamin D2. Feeding the diet with negative DCAD induced a compensated metabolic acidosis that attenuated the decline in blood ionized Ca (iCa) and serum total Ca (tCa) around calving, particularly in parous cows, whereas cows fed the diet with positive DCAD and supplemented with calcidiol had the greatest 1,25-dihydroxyvitamin D3 concentrations and the lowest iCa and tCa concentrations on d 1 and 2 postpartum. The acidogenic diet or calcidiol markedly increased urinary losses of tCa and tMg, and feeding calcidiol tended to increase colostrum yield and increased losses of tCa and tMg in colostrum. Cows fed the diet with negative DCAD had increased concentrations of serotonin and C-terminal telopeptide of type 1 collagen prepartum compared with cows fed the diet with positive DCAD. Concentrations of undercarboxylated and carboxylated osteocalcin and those of adiponectin did not differ with treatment. These results provide evidence that dietary manipulations can induce metabolic adaptations that improve mineral homeostasis with the onset of lactation that might explain some of the improvements observed in health and production when cows are fed diets with negative DCAD or supplemented with calcidiol.

Erratum to: A Rapid and Reliable Method for Total Protein Extraction from Succulent Plants for Proteomic Analysis.

The original version of this article unfortunately contains a mistake. The authors have inadvertently incorrectly listed the concentration of TCA in the acetone/TCA/β-ME solution in the materials and methods section of this paper. The TCA concentration in Sects. 2.3.2 and 2.3.5 should be 10% TCA, making the solution acetone/10% TCA/0.07% β-ME. It is now corrected with this erratum.

Use of calcitriol to maintain postpartum blood calcium and improve immune function in dairy cows

Our objectives were to determine the effects of an injectable formulation of calcitriol on mineral metabolism and immune function in postpartum Holstein cows that received an acidogenic diet prepartum to minimize hypocalcemia. In experiment 1, cows within 6 h of calving received calcitriol (0, 200, or 300 μg) to determine the dose needed to increase plasma concentrations of Ca; 300 μg was sufficient to sustain Ca for at least 3 d. In experiment 2, multiparous cows were assigned randomly to receive only vehicle (control, n = 25) or 300 μg of calcitriol (n = 25) subcutaneously within the first 6 h after calving. Blood was sampled before treatment and 12 h later, then daily until 15 d in milk (DIM), and analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), total Mg (tMg), and total P (tP), metabolites, and hormones. Urine was sampled in the first 7 DIM and analyzed for concentrations of tCa, tMg, and creatinine. Neutrophil function was evaluated in the first week postpartum. Dry matter intake and production performance were evaluated for the first 36 DIM. Calcitriol administration increased concentrations of calcitriol in plasma within 12 h of application from 51 to 427 pg/mL, which returned to baseline within 5 d. Concentrations of iCa and tCa increased 24 h after treatment with calcitriol. Concentrations of iCa (control = 1.08 vs. calcitriol = 1.20 mM), tCa (control = 2.23 vs. calcitriol = 2.33 mM), and tP (control = 1.47 vs. calcitriol = 1.81 mM) remained elevated in cows treated with calcitriol until 3, 5, and 7 DIM, respectively, whereas concentration of tMg (control = 0.76 vs. calcitriol = 0.67 mM) was less in calcitriol cows than control cows until 3 DIM. Concentrations of parathyroid hormone decreased in calcitriol cows compared with control cows (control = 441 vs. calcitriol = 336 pg/mL). Calcitriol tended to increase plasma concentrations of β-hydroxybutyrate and serotonin, but concentrations of glucose, nonesterified fatty acids, and C-telopeptide of type I collagen in plasma did not differ between treatments. Cows treated with calcitriol excreted more urinary tCa (control = 0.5 vs. calcitriol = 2.1 g/d) and tMg (control = 4.5 vs. calcitriol = 5.0 g/d) in the first 7 and 2 DIM, respectively, than control cows. Compared with control, calcitriol improved the proportion of neutrophils with oxidative burst (control = 31.9 vs. calcitriol = 40.6%), mean fluorescence intensity for oxidative burst (control = 90,900 vs. calcitriol = 99,746), and mean fluorescence intensity for phagocytosis (control = 23,887 vs. calcitriol = 28,080). Dry matter intake, yields of milk, and milk components did not differ between treatments. Administration of 300 μg of calcitriol at calving was safe and effective in increasing blood concentration of iCa and plasma concentrations of calcitriol, tCa, and tP for the first 6 d after treatment, and improved measures of innate immune function in early-lactation Holstein cows.

Quantification of 15 bile acids in lake charr feces by ultra-high performance liquid chromatography-tandem mass spectrometry.

Many fishes are hypothesized to use bile acids (BAs) as chemical cues, yet quantification of BAs in biological samples and the required methods remain limited. Here, we present an UHPLC-MS/MS method for simultaneous, sensitive, and rapid quantification of 15 BAs, including free, taurine, and glycine conjugated BAs, and application of the method to fecal samples from lake charr (Salvelinus namaycush). The analytes were separated on a C18 column with acetonitrile-water (containing 7.5mM ammonium acetate and 0.1% formic acid) as mobile phase at a flow rate of 0.25mL/min for 12min. BAs were monitored with a negative electrospray triple quadrupole mass spectrometer (Xevo TQ-S™). Calibration curves of 15 BAs were linear over the concentration range of 1.00-5,000ng/mL. Validation revealed that the method was specific, accurate, and precise. The method was applied to quantitative analysis of feces extract of fry lake charr and the food they were eating. The concentrations of analytes CA, TCDCA, TCA, and CDCA were 242.3, 81.2, 60.7, and 36.2ng/mg, respectively. However, other taurine conjugated BAs, TUDCA, TDCA, and THDCA, were not detected in feces of lake charr. Interestingly, TCA and TCDCA were detected at high concentrations in food pellets, at 71.9 and 38.2ng/mg, respectively. Application of the method to feces samples from lake charr supported a role of BAs as chemical cues, and will enhance further investigation of BAs as chemical cues in other fish species.

Gastrointestinal safety and tolerability of long-term gcsb-5 of dried extracts of six herbs in patients with osteoarthritis: A 24 weeks, multi-centers, single arm phase IV study

s / Osteoarthritis and Cartilage 23 (2015) A82eA416 A361 Conclusions: A single IA administration of 40 mg of FX006 maintained pharmacologically active synovial fluid concentrations of TCA for at least 12 weeks, while TCA IR produced levels that are below the lower limit of quantitation by 6weeks. These data underpin the differentiation of FX006 from TCA IR and provide pharmacokinetic basis for previously demonstrated prolongation and amplification of pain relief compared to TCA IR in OA patients following a single IA injection. FX006 also has the potential for an improved systemic safety profile as evidenced by peak plasma concentrations that are 40-fold lower than TCA IR at the same dose, seen in the aggregate of clinical studies with FX006 to date. 592 GASTROINTESTINAL SAFETY AND TOLERABILITY OF LONG-TERM GCSB-5 OF DRIED EXTRACTS OF SIX HERBS IN PATIENTS WITH OSTEOARTHRITIS: A 24 WEEKS, MULTI-CENTERS, SINGLE ARM PHASE IV STUDY C.-W. Ha y, Y.-B. Park y, H.-S. Kyung z, H.-C. Lim x, S.-E. Park k, M.-C. Lee ¶, Y.-Y. Won#, D.-C. Lee yy, C.-W. Kim zz, J.-G. Kim xx, J.-S. Kang kk, J.-K. Seon ¶¶, S.-I. Bin ##. y Samsung Med. Ctr., Sungkyunkwan Univ. Sch. of Med., Seoul, Republic of Korea; zKyungpook Natl. Univ. Hosp., Kyungpook Natl. Univ. Sch. of Med., Daegu, Republic of Korea; xKorea Univ. Guro Hosp., Korea Univ. Sch. of Med., Seoul, Republic of Korea; kDongguk Univ. Intl. Hosp., Dongguk Univ. Sch. of Med., Goyang, Republic of Korea; ¶ Seoul Natl. Univ. Hosp., Seoul Natl. Univ. Sch. of Med., Seoul, Republic of Korea; Ajou Univ. Hosp., Ajou Univ. Sch. of Med., Suwon, Republic of Korea; yy Yeungnam Univ. Hosp., Yeungnam Univ. Univ. Sch. of Med., Daegu, Republic of Korea; zzBusan Paik Hosp., Inje Univ. Sch. of Med., Seoul, Republic of Korea; xx Seoul Paik Hosp., Inje Univ. Sch. of Med., Seoul, Republic of Korea; kk Inha Univ. Hosp., Inha Univ. Sch. of Med., Incheon, Republic of Korea; Chonnam Natl. Univ. Hwasun Hosp., Chonnam Natl. Univ. Sch. of Med., Hwasun, Republic of Korea; Asan Med. Ctr., Ulsan Univ. Sch. of Med., Seoul,

The association of vibratory sense and muscle strength with the incidence and worsening of knee instability: the most study

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S377 ECGs and vital signs were unremarkable and similar across all treatments. Plasma TCA concentration across the FX006 doseswere linear and dose-dependent. Peak plasma concentrations achieved with 40 mg TCA IR were 10X of those seen with FX006 40 mg. Conclusions: It is demonstrated that sustained residency of TCA in the joint prolongs therapeutic effect. The 40 mg dose of FX006 produced an effect atWeek 12 ( 3.7) that was equivalent to the maximal effect of TCA IR at Week 4. Surprisingly, between Weeks 2 and 11, the analgesic effect of the 40mg dose of FX006 exceeded themaximal effect of TCA IR seen at Week 4. This observation suggests that prolonged occupation of the corticosteroid receptor may be associated with an enhanced analgesic effect. Further, this amplification of effect may constitute a meaningful clinical improvement relative toTCA IR as indicated by the 20% responder analysis for the 40 mg dose of FX006. A study is underway to determine the TCA concentrations in the joint at varying time points, and subsequent studies against placebo will define effect size and duration of action. Figure 1. Weekly Mean of Average Daily Pain Score (ADP) Figure 2. Proportion of Responders, >20% Improvement

Trans-Cinnamic Acid Increases Adiponectin and the Phosphorylation of AMP-Activated Protein Kinase through G-Protein-Coupled Receptor Signaling in 3T3-L1 Adipocytes

Adiponectin and intracellular 5′adenosine monophosphate-activated protein kinase (AMPK) are important modulators of glucose and fat metabolism. Cinnamon exerts beneficial effects by improving insulin sensitivity and blood lipids, e.g., through increasing adiponectin concentrations and AMPK activation. The underlying mechanism is unknown. The Gi/Go-protein-coupled receptor (GPR) 109A stimulates adiponectin secretion after binding its ligand niacin. Trans-cinnamic acid (tCA), a compound of cinnamon is another ligand. We hypothesize whether AMPK activation and adiponectin secretion by tCA is transmitted by GPR signaling. Differentiated 3T3-L1 cells were incubated with pertussis toxin (PTX), an inhibitor of Gi/Go-protein-coupling, and treated with different tCA concentrations. Treatment with tCA increased adiponectin and the pAMPK/AMPK ratio (p ≤ 0.001). PTX incubation abolished the increased pAMPK/AMPK ratio and adiponectin secretion. The latter remained increased compared to controls (p ≤ 0.002). tCA treatment stimulated adiponectin secretion and AMPK activation; the inhibitory effect of PTX suggests GPR is involved in tCA stimulated signaling.