Increasing the prepartum dose of rumen-protected choline: Effects of maternal choline supplementation on growth, feed efficiency, and metabolism in Holstein and Holstein × Angus calves.

Feeding pregnant cows rumen-protected choline (RPC) may have the potential to affect the growth and health of offspring, but little is known about the optimal dose, or the potential mechanisms of action. The objectives of this experiment were to 1) determine if increasing RPC supplementation during late gestation in multiparous Holstein cows would improve calf growth and 2) determine if maternal choline supplementation alters global DNA methylation patterns. Pregnant multiparous Holstein cows (n = 116) were randomly assigned to diets targeting 0g choline ion (0.0 ± 0.000 choline ion, %DM, control; CTL), 15g of choline ion (recommended dose; RD) from an established RPC product (0.10 ± 0.004 choline ion, %DM, RPC1RD; ReaShure, Balchem Corp.; positive control), or 15g (0.09 ± 0.004 choline ion, %DM, RPC2RD) or 22g (0.13 ± 0.005 choline ion, %DM, high dose; RPC2HD) of choline ion from a concentrated RPC prototype (RPC2; Balchem Corp.). Treatments were mixed into a total mixed ration and cows had ad libitum access via a roughage intake control system (Hokofarm Group, Marknesse, Netherlands). All female Holstein (n = 49) and Holstein × Angus calves (male, n = 18; female, n = 30) were enrolled and fed colostrum from a cow within the same treatment. Holstein calves and Holstein × Angus calves were fed an accelerated and traditional milk replacer program, respectively, and offered ad libitum access to calf starter. Jugular vein blood samples were collected, and body weight was measured at 7, 14, 28, 42, and 56 d of age. Categorical treatment and continuous effects of actual prepartum maternal choline ion intake were analyzed using mixed effect models. An interaction of treatment with sex, nested within breed, resulted in any choline treatment increasing the proportion of methylated whole blood DNA in male, but not female calves. Although 37% of Holstein calves across all treatments experienced abomasal bloat, no evidence for differences in health measurements (signs of respiratory disease and fecal consistency) were observed across treatments. During the first 2 wk of life in Holstein calves, RPC2HD tended to increase average daily gain (ADG) and feed efficiency (FE) compared with CTL and increasing maternal choline ion intake linearly increased ADG and FE. Maternal choline supplementation increased plasma glucose compared with CTL, while increasing serum insulin-like growth factor-1 and decreasing serum lipopolysaccharide binding protein at 7 d of age in Holstein calves. In Holstein × Angus calves, the effect of treatment on ADG tended to interact with sex: in males, RPC2HD increased ADG after 2 wk of life compared with CTL, without evidence of a treatment effect in female calves. Increasing maternal choline ion intake linearly increased ADG after 2 wk of age in male Holstein × Angus calves, while quadratically increasing FE in both sexes. Altered global DNA methylation patterns in male Holstein × Angus calves, and changes in blood metabolites in Holstein calves, provide 2 potential mechanisms for observed improvements in calf growth. Continuous treatment models demonstrated that the effects of maternal choline supplementation are sensitive to the amount of maternal choline ion intake, with greater benefit to calves observed at higher maternal intakes.

Increasing the prepartum dose of rumen-protected choline: Effects on milk production and metabolism in high-producing Holstein dairy cows.

Peripartum rumen-protected choline (RPC) supplementation is beneficial for cow health and production, yet the optimal dose is unknown. In vivo and in vitro supplementation of choline modulates hepatic lipid, glucose, and methyl donor metabolism. The objective of this experiment was to determine the effects of increasing the dose of prepartum RPC supplementation on milk production and blood biomarkers. Pregnant multiparous Holstein cows (n = 116) were randomly assigned to one of 4 prepartum choline treatments that were fed from -21 d relative to calving (DRTC) until calving. From calving until +21 DRTC, cows were fed diets targeting 0 g/d choline ion (control, CTL) or the recommended dose (15 g/d choline ion; RD) of the same RPC product that they were fed prepartum. The resulting treatments targeted: (1) 0 g/d pre- and postpartum [0.0 ± 0.000 choline ion, percent of dry matter (%DM); CTL]; (2) 15 g/d pre- and postpartum of choline ion from an established product (prepartum: 0.10 ± 0.004 choline ion, %DM; postpartum: 0.05 ± 0.004 choline ion, %DM; ReaShure, Balchem Corp.; RPC1RD▸RD); (3) 15 g/d pre- and postpartum of choline ion from a concentrated RPC prototype (prepartum: 0.09 ± 0.004 choline ion, %DM; postpartum: 0.05 ± 0.003 choline ion, %DM; RPC2, Balchem Corp.; RPC2RD▸RD); or (4) 22 g/d prepartum and 15 g/d postpartum from RPC2 [prepartum: 0.13 ± 0.005 choline ion, %DM; postpartum: 0.05 ± 0.003 choline ion, %DM; high prepartum dose (HD), RPC2HD▸RD]. Treatments were mixed into a total mixed ration, and cows had ad libitum access via a roughage intake control system (Hokofarm Group). From calving to +21 DRTC, all cows were fed a common base diet and treatments were mixed into the total mixed ration (supplementation period, SP). Thereafter, all cows were fed a common diet (0 g/d choline ion) until +100 DRTC (postsupplementation period, postSP). Milk yield was recorded daily and composition analyzed weekly. Blood samples were obtained via tail vessel upon enrollment, approximately every other day from -7 to +21 DRTC, and at +56 and +100 DRTC. Feeding any RPC treatment reduced prepartum dry matter intake compared with CTL. During the SP, no evidence for a treatment effect on energy-corrected milk (ECM) yield was found, but during the postSP, RPC1RD▸RD and RPC2RD▸RD treatments tended to increase ECM, protein, and fat yields. During the postSP, the RPC1RD▸RD and RPC2RD▸RD treatments tended to increase, and RPC2HD▸RD increased, the de novo proportion of total milk fatty acids. During the early lactation SP, RPC2HD▸RD tended to increase plasma fatty acids and ß-hydroxybutyrate concentrations, and RPC1RD▸RD and RPC2RD▸RD reduced blood urea nitrogen concentrations compared with CTL. The RPC2HD▸RD treatment reduced early lactation serum lipopolysaccharide binding protein compared with CTL. Overall, peripartum RPC supplementation at the recommended dose tended to increase ECM yield postSP, but no evidence was seen of an additional benefit on milk production with an increased prepartum dose of choline ion. The effects of RPC on metabolic and inflammatory biomarkers support the potential for RPC supplementation to affect transition cow metabolism and health and may support the production gains observed.

Inositols and metabolic disorders: From farm to bedside.

Inositol and its derivates are catching interest in metabolism since taking part in several physiological processes, including endocrine modulation. Through several mechanisms mostly mediated by insulin signaling, these compounds regulate the activities of several hormones and are essential in oocytes maturation. It is interesting to point out the contribution of an inositol deficiency in the development of several diseases, mainly in the metabolic and endocrine setting. Inositols derive from both diet and endogenous production; among causes of inositol deficiency reduced dietary intake, increased catabolism and/or excretion, decreased biosynthesis, inhibition of gut and cellular uptake and altered microbiota could be considered. Mounting direct and indirect evidence suggests that the two main isoforms (Myo-inositol-inositol, D-chiro-inositol) are implied in glycemic and lipidic metabolism and supplementation yield a beneficial effect on these parameters without hazards for health. Moreover, they have a role in polycystic ovary syndrome, acting as insulin-sensitizing agents and free radical scavengers, helping to regulate metabolism and promoting ovulation. The aim of this narrative review is to discuss the role of inositols in metabolic function disorders paying attention to whether these compounds could be efficacious and safe as a therapeutic agent with a focus on dietary intake and the role of gut microbiota.

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

Clinical-pathological changes in differentiated thyroid cancer (DTC) over time (1997-2010): data from the University Hospital "Maggiore della Carità" in Novara.

Differentiated thyroid cancer (DTC) is an important clinical entity in our population (Novara, Piedmont, Italy) which is characterized by important environmental influences, as iodine deficiency (ID) and subsequent supplementation, thyroiditis and occupational exposure. To evaluate the features of DTC in our population 20 years after the iodine-prophylaxis pondering the effects of the introduction of the new guidelines for diagnosis and management of DTC after 2005. 322 patients [244 females, age: mean (±SD) 53.8 ± 15.8 years] treated for DTC in a tertiary care center between 1997 and 2010 were retrospectively evaluated. Medical history, demographics, and pathological features were considered. Patients were subdivided into two groups: A (n = 139, diagnosis 1997­2005) and B (n = 183, diagnosis 2006­2010). The population of group A showed a mild ID, while normal iodine status was recorded in group B. A significant increase in histological tumor-associated thyroiditis was found from group A to B (p = 0.021). Recurrent or persistent diseases were found to be correlated with lymph nodes metastases and/or a distant disease at diagnosis, stimulated thyroglobulin levels at the first follow-up and an additional radioiodine therapy. Twenty percent of our patients were females employed in textile industries. The tumor-related inflammation and the occupational exposure should be considered as important factors in the pathogenesis of DTC. Further studies are required in order to confirm our findings.

Safety, efficacy, and cost of intraoperative cell salvage and autotransfusion after off-pump coronary artery bypass surgery: a randomized trial.

OBJECTIVE: We evaluated, in a randomized controlled trial, the safety and effectiveness of intraoperative cell salvage and autotransfusion of washed salvaged red blood cells after first-time coronary artery bypass grafting performed on the beating heart. METHODS: Sixty-one patients undergoing off-pump coronary artery bypass grafting surgery were prospectively randomized to autotransfusion (n = 30; receiving autotransfused washed blood from intraoperative cell salvage) or control (n = 31; receiving homologous blood only as blood-replacement therapy). Homologous blood was given according to unit protocols. RESULTS: The groups were well matched with respect to demographic and comorbid characteristics. Patients in the autotransfusion group had a significantly higher 24-hour postoperative hemoglobin concentration (11.9 g/dL; SD, 1.41 g/dL) than those in the control group (10.5 g/dL; SD, 1.37 g/dL) (mean difference, 1.02 g/dL; 95% confidence interval, 1.60-0.44 g/dL; P = .0007), as well as a 20% reduction in the frequency of homologous blood product use (11/31 vs 5/30; P = .095). Autotransfusion of washed red blood cells was not associated with any derangement of thromboelastograph values or laboratory measures of clotting pathway function (prothrombin time, activated partial thromboplastin time, and fibrinogen levels), increased postoperative bleeding, fluid requirements, or adverse clinical events. There was no statistical difference between groups in the total operation, hospitalization, and management costs per patient (median difference, USD 1015.90; 95% confidence interval, -USD 2260 to USD 206; P = .11). Conclusions Intraoperative cell salvage and autotransfusion was associated with higher postoperative hemoglobin concentrations, a modest reduction in transfusion requirements, no adverse clinical or coagulopathic effects, and no significant increase in cost compared with controls. This study supports its routine use in off-pump coronary artery bypass grafting surgery.

[Collateral effects of intraoperative hyperthermic chemotherapy in peritoneal carcinomatosis]. / Effetti collaterali della ipertermochemioterapia intraoperatoria nel trattamento della carcinosi peritoneale.

The association between chemotherapy and hypertermia produces a synergic effect. In this study the Authors present their experience, by the analysis of the results. From 1993 to 2000, 17 patients have been treated with surgery associated with hypertermic chemotherapy for peritoneal carcinomatosis. For the management of these patients a constant cooperation among surgeon, cardiologist and anaesthetist is very important.

[Anaesthesiologic problems about hyperthermic intraoperative intraperitoneal chemotherapy]. / Chemioipertermia intraperitoneale intraoperatoria: problematiche anestesiologiche.

The literature considers hyperthermic intraoperative intraperitoneal chemotherapy a safe and effective procedure for peritoneal carcinomatosis, but a technical improvement is necessary. Regional chemotherapy anticipates the "downfall" of tumoral cells in the peritoneum. The Authors considered 5 patients--female, age 27-45 years, ASA 2--operated of peritonectomy in ovaric neoplasia with peritoneal metastasis. The hyperthermic intraoperative intraperitoneal chemotherapy has been made at the end of the surgery with a hot solution (43 degrees C): 3000 ml of dextrose 1.5% with mytomicina C 25 mg e cysplatino 75 mg/m2. We considered variation of emodinamic parametres (blood pressure, central venous pressure, stroke volume, etc.) and biochemical parametres (Na, K, CI-, CO2, etc.). These parametres have been correlated with some complications: fistula, anastomotic leakage, pancreatitis and postoperative bleeding.

Specific glycoconjugates are present at the oolemma of the fertilization site in the egg of Discoglossus pictus (Anurans) and bind spermatozoa in an in vitro assay.

In the egg of the anuran Discoglossus pictus, the site of fertilization is restricted to the central portion of an animal hemisphere indentation (the dimple). Previous studies showed that the acrosome reaction of D. pictus sperm is triggered in the jelly, and yet sperm arrive at the dimple surface with the plasma membrane at an early stage of vesiculation. Reactivity of the dimple surface with specific lectins suggests that fucose might be utilized as a marker of glycoproteins located at the dimple surface. In this paper, proteins of the egg surface were labeled with the membrane impermeable sulfo-NHS-biotin. Four main bands of 200, 230, 260, and 270 kDa labeled only at the dimple surface, although they were detected in the cortex of the whole egg. The 270-kDa band reacted with Galanthus nivalis agglutinin only in the cortex of the dimple, suggesting that this band is differently glycosylated according to its localization. The alpha-l-fucose-specific lectin Ulex europaeus agglutinin I was utilized both in lectin blotting and in affinity chromatography and cross-reacted with the 200- and 270/260-kDa bands. Furthermore, two polypeptides were obtained by exposure of intact eggs to lysylendoproteinase C. They were also reactive to Ulex europaeus agglutinin I. The 200- and 270/260-kDa bands were eluted from the acrylamide gels and adsorbed to polystyrene beads. An assay for sperm binding to 200-kDa glycoprotein-bound beads was developed. Sperm stuck to the beads before but not after Ca-ionophore treatment. When the beads were coated with the 270/260-kDa glycoproteins, binding occurred after ionophore treatment. In these assays, the 200- and 270/260-kDa glycoproteins competitively inhibited sperm binding to the beads coated with the corresponding glycoprotein. These results indicate that the assayed glycoproteins, located either in the glycocalyx or in the plasma membrane of the fertilization site, are involved in sperm binding.

Warm blood hyperkalaemic reperfusion ('hot shot') prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery.

OBJECTIVE: A significant metabolic derangement occurs in the ischaemic-reperfused heart of patients undergoing coronary artery bypass surgery using cold blood cardioplegia. The aim of the present study was to investigate whether this effect could be reversed by complementing cold blood cardioplegia with a short terminal exposure of warm blood hyperkalaemic cardioplegia ('hot shot'). METHODS: Thirty-five patients undergoing primary elective coronary revascularisation were randomized to one of two different techniques of myocardial protection. In the cold blood group (n = 17) myocardial protection was induced using antegrade hyperkalaemic cold blood cardioplegic solution. In the hot shot group (n = 18) this was supplemented with a short exposure to hyperkalaemic warm blood cardioplegia prior to removal of the cross clamp. Intracellular substrates (ATP and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. RESULTS: Biopsies taken at the end of the period of myocardial ischaemia, when compared to control, did not show any significant change in the intracellular concentration of ATP (from 2.71 +/- 0.32 to 2.43 +/- 0.37 micromol g wet for cold blood group and from 2.6 +/- 0.3 to 2.5 +/- 0.34 micromol/g wet weight for hot shot group) or total free intracellular amino acids pool (from 33.0 +/- 1.4 to 30.0 +/- 1.4 micromol/g wet weight for cold blood group and from 34.0 +/- 1.4 to 34.5 +/- 2.3 micromol/g wet weight for hot shot group). Upon reperfusion, however, there was a significant fall in ATP (23.7 +/- 1.6 micromol/g wet weight amino acids, P < 0.05) and in amino acids (1.53 +/- 0.24 micromol/g wet weight, P < 0.05) in the group receiving only cold blood cardioplegia but not in the hot shot group (2.27 +/- 0.27 micromol/g wet weight ATP and 30.5 +/- 1.6 micromol/g wet weight amino acids). CONCLUSIONS: The data suggest that warm blood hyperkalaemic reperfusion hot shot prevents myocardial metabolic derangement seen during coronary artery surgery.

Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery.

OBJECTIVE: The influence of the addition of magnesium on myocardial protection with intermittent antegrade warm blood hyperkalaemic cardioplegia in patients undergoing coronary artery surgery was investigated and compared with intermittent antegrade warm blood hyperkalaemic cardioplegia only. METHODS: Twenty-three patients undergoing primary elective coronary revascularization were randomized to one of two different techniques of myocardial protection. In the first group, myocardial protection was induced using intermittent antegrade warm blood hyperkalaemic cardioplegia. In the second group, the same technique was used except that magnesium was added to the cardioplegia. Intracellular substrates (ATP, lactate and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. RESULTS: There were no significant changes in the intracellular concentration of ATP or free amino acid pool in biopsies taken at the end of the period of myocardial ischaemia. However, the addition of magnesium prevented the significant increase in the intracellular concentration of lactate seen with intermittent antegrade warm blood hyperkalaemic cardioplegia. Upon reperfusion there was a significant fall in ATP and amino acid concentration when the technique of intermittent antegrade warm blood hyperkalaemic cardioplegia was used but not when magnesium was added to the cardioplegia. CONCLUSIONS: This work shows that intermittent antegrade warm blood hyperkalaemic cardioplegia supplemented with magnesium prevents substrate derangement early after reperfusion.