Oral administration of melatonin increases plasma calcium and magnesium and improves bone metabolism in aged male mice

We previously reported that the oral administration of melatonin from 4 to 20 months to male mice improved femoral bone strength and bone density during the aging. Additionally, melatonin receptor, MT2, was immunologically detected in both osteoblasts and osteoclasts of the mouse femoral bone. Thus, melatonin can act on both osteoblasts and osteoclasts to maintain bone strength during the aging process. Here, we analyzed plasma calcium (Ca2+), magnesium (Mg2+), and inorganic phosphorus ([PO4]3-) in 20-month-old male mice with or without administration melatonin (15-20 mg/kg/day) in drinking water. We found that plasma Ca2+ and Mg2+ levels in melatonin-treated mice increased significantly as compared with control mice. In [PO4]3-, melatonin administration tended to increase its plasma level, but did not reach statistical significance. The potential association between these divalent ions and metabolism markers of femoral bone was also examined. In the femoral diaphysis, the plasma Ca2+ and Mg2+ concentrations were positively correlated with periosteal and endosteal circumference which were significantly associated with the Strength Strain Index. Therefore, melatonin treatment enlarged femoral diaphysis and enhanced bone strength by increasing mineral depositions. In addition, the plasma melatonin levels were significantly positive correlation with total bone density and critical thickness in the femoral diaphysis. Since we had not observed the primary trabecular bone and osteoclasts in 20-month-old mice previously, it is suggested that plasma Ca2+ and Mg2+ are not elevated due to bone resorption. The increased plasma Ca2+ and Mg2+ by melatonin may originate from the intestinal absorption of these ions since melatonin binds to the vitamin D3 receptor, its activation is known to promote the intestinal absorption of Ca2+.

Effects of some management factors (Housing condition and watering regimen) on blood parameters of desert goats

This study aimed to assess the effects of housing condition and watering regimen on some blood parameters during the period May 2018- February 2019. Desert goat Package Cell Volume% (PCV %) were highest during January, February and lowest during May, and August. Goats had the highest (P<0.001) blood Hemoglobin (Hb%) during May and July with very slight fluctuations throughout the seven months of the experimental period. Goats under shade had comparatively higher PCV% and slightly lower Hb% in comparison with those under direct sunlight. Plasma Calcium was low during February and January and rose during December with higher levels during May, June and July. Goat plasma phosphorus concentrations followed an opposite picture being highest (P<0.01) during October, December, and February and lowest (P<0.01) during other months. Plasma Calcium (Ca) and Phosphorus (P) concentrations were slightly (P>0.05) higher for goats under shade compared with those under direct sunlight. The main effects of months on blood metabolites were highly significant (P<0.01). The highest goat blood protein was during, June-July and lowest (P<0.01) during other months. Goat blood albumen levels were highest (P<0.001) for August- September- October and lowest for January- February whereas blood glucose levels were highest (P<0.01) during January- February and with very slight fluctuations throughout the seven months of the experimental period. Blood protein, blood albumin and blood glucose levels were relatively higher (P>0.05) for goats under shade compared with those under direct sunlight. Goats watered everyday had slightly lower blood protein and albumin and slightly higher blood glucose in comparison with goats watered every other day.

Practice patterns for chronic hypoparathyroidism: data from patients and physicians in France

Context. Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines. Objective. To describe the practice patterns and their compliance with international guidelines. Design. Cohort studies: Épi-Hypo (118 Physicians and 107 patients, from 09/2016 to 12/2019) and ePatients (110 patients, November 2019). Methods. Internet-based cohorts involving all settings at a nationwide level (France). Participants were i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the ii) Épi-Hypo study (Épi-Hypo 2019 patients) or iii) Hypoparathyroidism France, the national representative association (ePatients). Results. The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%) or miscellaneous (4%). Forty-five percent were practicing in public universities. The median number of pharmaceutical drug classes prescribed was 3 per patient. The combination of active vitamin D and calcium salt was given to 59% and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32% and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion. Conclusions. The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target not only endocrinologists. Full adherence to the guidelines is low in France.

Extreme hypercalcaemia caused by immobilisation due to acute spinal cord injury

Hypercalcaemia due to immobilisation is an uncommon diagnosis and requires extensive evaluation to rule out common causes of hypercalcaemia such as primary hyperparathyroidism and malignancy.We report an unusual case of profound hypercalcaemia due to immobilisation in a young man due to acute spinal cord ischaemia, leading to paraplegia. Other causes of hypercalcaemia were ruled out and elevated bone turnover markers supported our hypothesis. Conventional treatment with intravenous fluids, bisphosphonates and diuretics was insufficient. Subcutaneous calcitonin lowered the plasma calcium acutely and was continued for 8 weeks. Subsequent normocalcaemia was sustained for 2 years.

Prolactin induced cyto-architectural changes in the corpuscles of Stannius of stinging catfish, Heteropneustes fossilis acclimated to different calcium media

Adult fish Heteropneustes fossilis were divided into 4 groups –(i) Group A: kept in artificial freshwater and daily injected intraperitoneally with vehicle; (ii) Group B: kept in artificial freshwater and were daily injected intraperitoneally with 0.1 mg/100 g body wt of oProlactin; (iii) Group C: maintained in calcium-deficient freshwater and daily injected intraperitoneally with vehicle; (iv) Group D: kept in calcium-deficient freshwater and daily injected intraperitoneally with 0.1 mg/100 g body wt of oProlactin. Blood samples were taken 2 h after the last injection on 1, 3, 5, 10 and 15 days of the treatment. Plasma calcium levels were analyzed. The corpuscles of Stannius (CS) were fixed for histological studies. Artificial freshwater: The plasma calcium levels of vehicle-injected specimens (group A) remained unaltered throughout the experiment. Following prolactin treatment (group B) the plasma calcium levels progressively increased from day 3 to day 5. The values became normocalcemic at day 10 and day 15. After day 5 following prolactin administration (group B), the nuclear volume of AF-positive cells increased and the cells were seen degranulated. After day 10, there was an increased dilatation of sinusoids and the nuclear volume of AF-positive cells showed further increase. On day 15, these changes were exaggerated. The AFnegative cells of the corpuscles of Stannius of prolactin-treated fish (group B) showed no change in their histological structure and nuclear volume. Calcium-deficient freshwater: The plasma calcium level decreased in vehicle-injected fish (group C) from day 1 to day 3 (as compared to level of the fish kept in artificial freshwater). Thereafter, the level increased from day 5 resulting in hypercalcemia at day 10 and day 15. In prolactin treated fish (group D) the plasma calcium level indicated progressive increase from day 5 to day 15. In the vehicle-injected fish (group C) the AF-positive cells of corpuscles of Stannius showed accumulati

1002 Calcium administration in Major haemorrhage Protocol

Introduction Calcium gluconate is an essential part of the major haemorrhage protocol (MHP). It minimizes the exacerbation of transfusion coagulopathies due to the citrate preservative. As fifty percent of trauma patients present with hypocalcaemia prior to transfusion, the risk is pertinent. Given the importance of the issue, surprisingly current guidelines remain sparse. We analysed the percentage of patients who received calcium and their hypocalcaemia incidence. Method A Retrospective review of red traumas during June to August 2019. The frequency of MHP and the patient’s ionised plasma calcium levels on VBG (1.15-1.26mmol/L) were identified. Our standard stated 100% of MHP should receive calcium. A massive transfusion was defined as 10 red blood cells units in 24 hours or 4 blood products within 30mins. Results 27 red traumas were accepted to audit, MHP was activated in 85%. Out of these 75% received calcium and on average after 6.4 units of blood products. The incidence of ionised hypocalcaemia in all MHP patients was 67%. Conclusions We identified a standard that supplementary calcium should be supplemented in all MHPs. Hypocalcaemia was more frequency than our research stipulated. Improvement needs to be made to meet standards. We recommend incorporation of Calcium gluconate into major haemorrhage pack and transfusion guidelines.

MO1020EFFICACY OF CALCITRIOL COMPARING TO ALFACALCIDOL FOR THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN CHILDREN ON PERITONEAL DIALYSIS

Background and Aims Active vitamin D analogues are used routinely for the treatment of secondary hyperparathyroidism in children with end-stage renal disease (ESRD) on peritoneal dialysis (PD). Calcitriol is preferred active form of vitamin D, while data on efficacy of alfacalcidol in children on PD are limited. The aim of this study was to compare the efficacy of these two active vitamin D analogues for the treatment of secondary hyperparathyroidism in children on PD. Method This retrospective cohort study included data from 26 pediatric patients under 18 years of age with ESRD on PD who were treated at the National Research Center for Maternal and Child Health, Astana, Kazakhstan. Patients were allocated by initial treatment into two groups: oral alfacalcidol (n=21) and oral calcitriol (n=5). The first step of the study was to compare the efficacy of treatment between this two groups 3 and 6 months after. The second step was to compare the efficacy of calcitriol in subgroup of patients from alfacalcidol group who were switched to calcitriol later (n=12). The following characteristics were analyzed: parathyroid hormone (PTH), total plasma calcium, ionized plasma calcium, plasma phosphorus, initial dose of active vitamin D and corrected dose of vitamin D after 3 months. Independent t-test and repeated measures Anova were used for comparison between alfacalcidol and calcitriol groups. To compare data in subgroup between baseline and 3 months after conversion from alfacalcidol to calcitriol we used paired Student t-test. Results The mean age and baseline characteristics were no different between alfacalcidol and calcitriol groups (Table 1). The initial dose of alfacalcidol was 2.42±1.03 µg/week (0.157±0.097 µg/kg/week) and 2.09±0.74 µg/week (0.105±0.039 µg/kg/week) for calcitriol were not significantly different (P=0.5 and P=0.25 respectively). After 3 months of treatment there was statistically significant decrease of PTH level in calcitriol group 180±168 pmol/L comparing to alfacalcidol group 869±670 pmol/L (P=0.006). After 6 months, there was statistically significant decrease of PTH level in calcitriol group 261±259 pmol/L in contrast with alfacalcidol group 1080±716 pmol/L (P=0.047) and rise in total calcium in calcitriol group 2.46±0.17 mmol/L compared with alfacalcidol group 2.09±0.25mmol/L (P=0.035). The mean dose of calcitriol was also significantly lower as opposed to alfacalcidol dose: 0.04±0.039 µg/kg/week and 0.17±0.076 µg/kg/week respectively (P=0.002). The median age of children who were switched from alfacalcidol to calcitriol were significantly younger comparing with those who continued alfacalcidol (5±4.6 and 10±4.3 years of age respectively (P=0.022)). 3 months after conversion there was significant increase in ionized calcium level and decrease in PTH level comparing with baseline (Table 2). The dose of alfacalcidol before and dose of calcitriol after switch were differed (0.18±0.1 µg/kg/week and 0.13±0.05 µg/kg/week respectively, P=0.025) Conclusion Calcitriol showed superior efficacy for the treatment of secondary hyperparathyroidism in children on PD with the dose 4.25 times lower that of alfacalcidol. Alfacalcidol had limited efficacy for the treatment of secondary hyperparathyroidism in younger children when prescribed in recommended doses.

Feeding a Negative Dietary Cation-Anion Difference to Female Goats Is Feasible, as Indicated by the Non-Deleterious Effect on Rumen Fermentation and Rumen Microbial Population and Increased Plasma Calcium Level

The dietary cation-anion difference (DCAD) has been receiving increased attention in recent years; however, information on rumen fermentation, cellulolytic bacteria populations, and microbiota of female goats fed a negative DCAD diet is less. This study aimed to evaluate the feasibility of feeding a negative DCAD diet for goats with emphasis on rumen fermentation parameters, cellulolytic bacteria populations, and microbiota. Eighteen female goats were randomly blocked to 3 treatments of 6 replicates with 1 goat per replicate. Animals were fed diets with varying DCAD levels at +338 (high DCAD; HD), +152 (control; CON), and −181 (low DCAD; LD). This study lasted 45 days with a 30-d adaption and 15-d trial period. The results showed that the different DCAD levels did not affect the rumen fermentation parameters including pH, buffering capability, acetic acid, propionic acid, butyric acid, sum of acetic acid, propionic acid, and butyric acid, or the ratio of acetic acid/propionic acid (p > 0.05). The 4 main ruminal cellulolytic bacteria populations containing Fibrobacter succinogenes, Ruminococcus flavefaciens, Butyrivibrio fibrisolvens, and Ruminococcus albus did not differ from DCAD treatments (p > 0.05). There was no difference in bacterial richness and diversity indicated by the indices Chao, Abundance Coverage-based Estimator (Ace), or Simpson and Shannon, respectively (p > 0.05), among 3 DCAD levels. Both principal coordinate analysis (PCoA) weighted UniFrac distance and unweighted UniFrac distance showed no difference in the composition of rumen microbiota for CON, HD, and LD (p > 0.05). At the phylum level, Bacteroidetes was the predominant phylum followed by Firmicutes, Synergistetes, Proteobacteria, Spirochaetae, and Tenericutes, and they showed no difference (p > 0.05) in relative abundances except for Firmicutes, which was higher in HD and LD compared to CON (p < 0.05). At the genus level, the relative abundances of 11 genera were not affected by DCAD treatments (p > 0.05). The level of DCAD had no effect (p > 0.05) on growth performance (p > 0.05). Urine pH in LD was lower than HD and CON (p < 0.05). Goats fed LD had higher plasma calcium over HD and CON (p < 0.05). In summary, we conclude that feeding a negative DCAD has no deleterious effects on rumen fermentation and rumen microbiota and can increase the blood calcium level, and is therefore feasible for female goats.