Update: Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial.

BACKGROUND: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes. METHODS/DESIGN: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMCLBM) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMCLBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. DISCUSSION: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za TRIAL STATUS: Participant follow-up completed; data analysis ongoing.

Encapsulation of a small-molecule drug based on substituted 2-aminothiophenes in calcium carbonate carriers for therapy of melanoma.

Although small molecule drugs are widely used in chemotherapy, their low bioavailability, low-concentrated dose in the tumor zone, systemic toxicity, and chemoresistance can significantly limit the therapeutic outcome. These drawbacks can be overcome by two main strategies: (i) development of novel therapeutic molecules with more significant antitumor activity than currently available drugs and (ii) loading chemotherapeutic agents into drug delivery systems. In this study, we aimed to encapsulate a highly prospective small molecule drug based on substituted 2-aminothiophene (2-AT) into calcium carbonate (CaCO3) microparticles (MPs) for the treatment of melanoma tumors. In particular, we have optimized the encapsulation of 2-AT into MPs (2-AT@MPs), studied drug release efficiency, investigated cellular uptake, and evaluated in vivo biodistribution and tumor inhibition efficiency. In vitro results revealed that 2-AT@MPs were able to penetrate into tumor spheroids, leading to prolonged release of 2-AT. By performing intratumoral injection of 2-AT@MPs we observed significant melanoma suppressions in murine models: ∼0.084 cm3 for 2-AT@MPs at a dose of 0.4 g kg-1versus ∼1.370 cm3 for untreated mice. In addition, the 2-AT@MPs showed negligible in vivo toxicity towards major organs such as heart, lung, liver, kidney, and spleen. Thus, this work provided an efficient strategy for the improved chemotherapy of solid tumors by using an encapsulated form of small molecule drugs.

Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial.

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups -5.61 mg/L; 95% CI -11.01 to -0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

A Randomized Trial of Calcium Plus Vitamin D Supplementation and Risk of Ductal Carcinoma In Situ of the Breast.

Background: The effect of calcium plus vitamin D (CaD) supplementation on risk of ductal carcinoma in situ (DCIS) of the breast, a nonobligate precursor of invasive ductal carcinoma, is not well understood. In this secondary analysis, we examined this association in the Women's Health Initiative CaD trial over approximately 20 years of follow-up. Methods: A total of 36 282 cancer-free postmenopausal women (50-79 years) were randomly assigned to daily (d) calcium (1000 mg) plus vitamin D (400 IU) supplementation or to a placebo. Personal supplementation with vitamin D (≤600 IU/d, subsequently raised to 1000 IU/d) and calcium (≤1000 mg/d) was allowed. The intervention phase (median = 7.1 years), was followed by a postintervention phase (additional 13.8 years), which included 86.0% of the surviving women. A total of 595 incident DCIS cases were ascertained. Hazard ratios (HRs) plus 95% confidence intervals (CIs) were calculated. Results: The intervention group had a lower risk of DCIS throughout follow-up (HR = 0.82, 95% CI = 0.70 to 0.96) and during the postintervention phase (HR = 0.76, 95% CI = 0.61 to 0.94). The group that used CaD personal supplements in combination with the trial intervention had a lower risk of DCIS compared with the trial placebo group that did not use personal supplementation (HR = 0.72, 95% CI = 0.56 to 0.91). Conclusions: CaD supplementation in postmenopausal women was associated with reduced risk of DCIS, raising the possibility that consistent use of these supplements might provide long-term benefits for the prevention of DCIS.

Multispectral Assessment of Sweet Pepper (Capsicum annuum L.) Fruit Quality Affected by Calcite Nanoparticles.

Sweet pepper (Capsicum annuum L.) is one of the most important vegetable crops in the world because of the nutritional value of its fruits and its economic importance. Calcium (Ca) improves the quality of sweet pepper fruits, and the application of calcite nanoparticles in agricultural practice has a positive effect on the morphological, physiological, and physicochemical properties of the whole plant. The objectives of this study were to investigate the effect of commercial calcite nanoparticles on yield, chemical, physical, morphological, and multispectral properties of sweet pepper fruits using a combination of conventional and novel image-based nondestructive methods of fruit quality analysis. In the field trial, two sweet pepper cultivars, i.e., Soroksari and Kurtovska kapija, were treated with commercial calcite nanoparticles (at a concentration of 3% and 5%, calcite-based foliar fertilizer (positive control), and water (negative control) three times during vegetation). Sweet pepper fruits were harvested at the time of technological and physiological maturity. Significant differences were observed between pepper cultivars as well as between harvests times. In general, application of calcite nanoparticles reduced yield and increased fruit firmness. However, different effects of calcite nanoparticles were observed on almost all properties depending on the cultivar. In Soroksari, calcite nanoparticles and calcite-based foliar fertilizers significantly increased N, P, K, Mg, Fe, Zn, Mn, and Cu at technological maturity, as well as P, Ca, Mg, Fe, Zn, Mn, Cu, and N at physiological maturity. However, in Kurtovska kapija, the treatments increased only Ca at technological maturity and only P at physiological maturity. The effect of treatments on fruit morphological properties was observed only at the second harvest. In Soroksari, calcite nanoparticles (3% and 5%) increased the fruit length, minimal circle area, and minimal circle radius, and it decreased the fruit width and convex hull compared to the positive and negative controls, respectively. In Kurtovska kapija, calcite nanoparticles increased the fruit width and convex hull compared to the controls. At physiological maturity, lower anthocyanin and chlorophyll indices were found in Kurtovska kapija in both treatments with calcite nanoparticles, while in Soroksari, the opposite effects were observed.

Comparative Pharmacokinetics/Pharmacodynamics of Fixed-Dose Combination of Esomeprazole and Calcium Carbonate (AD-206) to the Conventional Esomeprazole.

PURPOSE: Proton pump inhibitors (PPIs) are used for the treatment of acid-related disorders. Demands for enhanced stability and faster onset led to the development of AD-206, a fixed-dose combination of a PPI (esomeprazole) with an antacid salt (calcium carbonate). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of AD-206 (Addpharma) with conventional esomeprazole (Nexium®, AstraZeneca). MATERIALS AND METHODS: A randomized, open-label, two-treatment, two-sequence crossover study was conducted with 2 different doses of esomeprazole at 20 and 40 mg with a fixed calcium carbonate dose of 600 mg in AD-206. Forty-four subjects were included in each dose group and randomly received either AD-206 or the conventional esomeprazole for 7 consecutive days in each period. After a single- and multiple-dose, blood samples for the PK analysis were analyzed, and 24-hour intragastric pH monitoring was conducted. RESULTS: The systemic exposure of esomeprazole after a multiple-dose of AD-206 was similar to that of the conventional esomeprazole in both doses, but the time to reach the peak concentration was faster in AD-206. The percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the dose was not significantly different between the AD-206 and the conventional esomeprazole after a single- and multiple-dose for both doses, and the time to reach pH 4 was faster for AD-206. CONCLUSION: AD-206 showed a similar systemic exposure and suppression of gastric acid secretion after a multiple-dose compared to the conventional esomeprazole.

Inflammation Modulation by Vitamin D and Calcium in the Morphologically Normal Colorectal Mucosa of Patients with Colorectal Adenoma in a Clinical Trial.

Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. We tested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group (P = 0.001), 46% in the calcium group (P = 0.002), and 34% in the calcium + vitamin D group (P = 0.03), relative to the placebo group. Among individuals with the functional vitamin D-binding protein isoform DBP2 (GC rs4588*A), the COX-2/15-HPDG ratio decreased 70% (P = 0.0006), 75% (P = 0.0002), and 60% (P = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorably modulate the balance of expression of COX-2 and 15-HPGD-biomarkers of inflammation that are strongly linked to colorectal carcinogenesis-in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform). PREVENTION RELEVANCE: Supplemental calcium and vitamin D reduce indicators of cancer-promoting inflammation in normal colorectal tissue in humans, thus furthering our understanding of how they may help prevent colorectal cancer.

A Novel Resorbable Composite Material Containing Poly(ester-co-urethane) and Precipitated Calcium Carbonate Spherulites for Bone Augmentation-Development and Preclinical Pilot Trials.

Polyurethanes have the potential to impart cell-relevant properties like excellent biocompatibility, high and interconnecting porosity and controlled degradability into biomaterials in a relatively simple way. In this context, a biodegradable composite material made of an isocyanate-terminated co-oligoester prepolymer and precipitated calcium carbonated spherulites (up to 60% w/w) was synthesized and investigated with regard to an application as bone substitute in dental and orthodontic application. After foaming the composite material, a predominantly interconnecting porous structure is obtained, which can be easily machined. The compressive strength of the foamed composites increases with raising calcium carbonate content and decreasing calcium carbonate particle size. When stored in an aqueous medium, there is a decrease in pressure stability of the composite, but this decrease is smaller the higher the proportion of the calcium carbonate component is. In vitro cytocompatibility studies of the foamed composites on MC3T3-E1 pre-osteoblasts revealed an excellent cytocompatibility. The in vitro degradation behaviour of foamed composite is characterised by a continuous loss of mass, which is slower with higher calcium carbonate contents. In a first pre-clinical pilot trial the foamed composite bone substitute material (fcm) was successfully evaluated in a model of vertical augmentation in an established animal model on the calvaria and on the lateral mandible of pigs.

Calcium Supplement by Tetracycline guided amorphous Calcium Carbonate potentiates Osteoblast promotion for Synergetic Osteoporosis Therapy.

Background: The calcium supplement is a clinically approved approach for osteoporosis therapy but usually requires a large dosage without targetability and with poor outcome. This modality is not fully explored in current osteoporosis therapy due to the lack of proper calcium supplement carrier. Methods: In this study, we constructed a tetracycline (Tc) modified and simvastatin (Sim) loaded phospholipid-amorphous calcium carbonate (ACC) hybrid nanoparticle (Tc/ACC/Sim). Results: The resulted Tc/ACC/Sim was able to enhance its accumulation at the osteoporosis site. Most importantly, the combination of calcium supplement and Sim offered synergetic osteoblast promotion therapy of osteoporosis with advanced performance than non-targeted system or mono therapy. Conclusion: This platform provides an alternative approach to stimulate bone formation by synergetic promotion of osteoblast differentiation using calcium supplement and Sim.

Indigenous Lactic Acid Bacteria Isolated from Spontaneously Fermented Goat Milk as Potential Probiotics.

BACKGROUND AND OBJECTIVE: Lactic Acid Bacteria (LAB) isolated from goat milk have been known to have various medicinal properties, therefore they are considered as a source of potential probiotics. This research was aimed at evaluating and identifying the LAB isolated from spontaneously fermented goat milk as potential probiotics. MATERIALS AND METHODS: The fresh goat milk fermented for 4 days was serially diluted, plated on de Man Rogosa and Sharpe (MRS) agar supplemented with 1% CaCO3 as selective medium, then purified accordingly. The isolated LAB were screened for their potential to inhibit enteric pathogen bacteria using well diffusion method. Their capabilities to withstand the bile salt and acid environment were also evaluated. The production of organic acids was also assessed. The potential probiotics were identified molecularly using 16S rRNA. RESULTS: The study confirmed that LAB isolated from spontaneous fermentation of goat milk was Lactobacillus plantarum based on 16S rRNA gene marker. This bacterium showed antimicrobial activity against indicator bacteria, ability to live after exposure in bile salt solution and resistance to low acidic environment. The organic acids produced by this bacterium were lactic, acetic, propionic and butyric acids. CONCLUSION: This study concluded that Lactobacillus plantarum YN.1.3 can be further investigated as potential probiotic as it showed antimicrobial activity, withstood the acidic environment and bile salt solution, as well as produced organic acids.

Preparation of lentinan-calcium carbonate microspheres and their application as vaccine adjuvants.

Adjuvants improve vaccine potency by enhancing immunogenicity and sustaining long-term immune responses. Lentinan (LNT), a ß-1,3-glucohexaose with ß-1,6-branches, is extracted from the mushroom Lentinus edodes and functions as an effective immunostimulatory drug. Previous studies have demonstrated the adjuvant activity of calcium carbonate (CaCO3) microspheres as well as their use as antigen delivery systems. In this study, we successfully loaded CaCO3 microspheres with LNT and evaluated their physicochemical characteristics prior to the adsorption of ovalbumin. Our experimental results demonstrated that LNT-CaCO3 significantly enhanced lymphocyte proliferation, and boosted the frequency of CD69 + B cells and the ratio of CD4+ to CD8 + T cells in spleen lymphocytes. Moreover, LNT-CaCO3 unexpectedly induced the secretion of IgG and Th-associated cytokines (IL-2, IL-4, IFN-γ, and TNF-α) in immunized mice. Therefore, LNT-CaCO3 microspheres induce robust cellular and humoral immune responses and have potential utility as vaccine delivery systems.

A nanoplatform with tumor-targeted aggregation and drug-specific release characteristics for photodynamic/photothermal combined antitumor therapy under near-infrared laser irradiation.

Due to their high biocompatibility, high spatial resolution, chromatographic capability, and adjustable size and morphology, magnetic nanoparticles have become the most promising nanomaterials for clinical application in noninvasive imaging and drug delivery for the treatment of malignant tumors. Herein, a novel magnetic nanoparticle coated with calcium carbonate was prepared and loaded with near-infrared drugs to be used as a multifunctional theranostic nanoplatform for the diagnosis and treatment of malignant tumors. Then, these drug-loaded nanoparticles were used for combined photodynamic/photothermal therapy by intravenous administration that was simultaneously guided by fluorescence/MR imaging. Due to the targeted induction of the external magnetic field and tumor response degradation of the calcium carbonate layer, the nanoprobe demonstrated excellent tumor targeting and greatly improved drug aggregation at the tumor site. Finally, single wavelength-mediated photothermal/photodynamic therapy was applied to liver cancer model mice, ultimately achieving an exciting antitumor therapeutic effect. This study may promote further exploration of nanoplatforms based on magnetic nanoparticles for clinical application in the treatment of malignant tumors.

Combined ionized calcium and PTH evaluation in the management of post-thyroidectomy hypocalcemia.

BACKGROUND: The aim of our study was to investigate the postoperative course of calcium and parathyroid hormone (PTH) levels after total thyroidectomy to define a proper and low cost protocol. METHODS: We studied 144 patients who underwent total thyroidectomy between 2007 and 2010. Ionized calcium was determined preoperatively and on day 1 (POD1), day 2 (POD2) and day 7 (POD7) postoperatively; PTH preoperatively and on POD7. Patients with ionized calcium ≤1.11 mmol/L were considered hypocalcemic and treated only if symptoms, ≤1 mmol/L were treated in all cases. RESULTS: Ionized calcium and PTH declined postoperative in all patients compared to preoperative levels (P=0.000). Ionized calcium increased on POD7 compared to POD1 and POD2 (P=0.000). All hypocalcemic untreated 30 patients returned normocalcemic on POD7. Thirty-eight hypocalcemic patients were treated but 23 (61%) safely suspended therapy on POD7. We tested PTH and ionized calcium as independent factors of prolonged hypocalcemia (that required therapy beyond 7 days) with the following results (sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy): PTH ≤11 pg/mL (80%, 100%, 100%, 96% and 97%, respectively), ionized calcium ≤1.11 mmol/L (80%, 88%, 59%, 95%, and 87%, respectively) and ionized calcium ≤1 mmol/L (28%, 100%, 100%, 87% and 88%, respectively). CONCLUSIONS: Our data show that our protocol, including serum ionized calcium on 1st, 2nd, 7th days and PTH on 7th day after surgery, is safe and low cost and therefore may be useful in the post-surgical management of total thyroidectomy.

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

Limestone particle size, calcium and phosphorus levels, and phytase effects on live performance and nutrients digestibility of broilers.

Limestone particle size (PS) affects its solubility and thus can influence broiler performance by altering the rate of calcium (Ca) release into the gastrointestinal tract. The objective of this research was to determine, using 2 × 2 × 2 factorial arrangement, the influence of PS (fine and coarse) and supplemented phytase (0 and 1,000 FYT/kg) in diets formulated with 2 Ca and Pi levels (positive control [PC]; negative control [NC]) on live performance, bone ash, and apparent ileal nutrients digestibility (AID). Starter PC: 0.9 Ca and 0.45 Pi; NC: 0.72 Ca and 0.03 Pi. Grower PC: 0.76 Ca and 0.38 Pi; NC: 0.58 Ca and 0.23 Pi. The 8 diets were assigned randomly to a total of 1,512 birds, with 21 birds per pen and 9 pens per treatment. The main effects of PS and Ca and Pi levels had no influence on feed intake (FI), body weight gain (BWG), or feed conversion ratio. Adding phytase improved BWG by 8 g and 50 g and FI by 25 g and 56 g at 0-14 D (P ≤ 0.05) and 0-35 D (P ≤ 0.05), respectively. Interaction between Ca and Pi levels and phytase improved BWG and FI for 0-14 D (P ≤ 0.05) and BWG during 15-28 D (P ≤ 0.05) for PC without phytase and for PC and NC with phytase when compared with NC without phytase. Birds fed PC without phytase, or either PC or NC with phytase were about 96 g heavier than NC without phytase. Birds fed either PC or NC diet with coarse limestone or PC with fine limestone gained approximately 14 g more (P ≤ 0.05) than birds fed NC with fine limestone for BWG at 0-14 D (P ≤ 0.05). Phytase increased tibia bone ash (14 D) by 1% (P ≤ 0.05). AID of Ca and Pi at 14 D was improved (P ≤ 0.05) by 66% when phytase was added to coarse limestone. Results indicate that phytase improved broiler performance without being affected by PS. Furthermore, phytase had greater influence on coarse limestone than on fine limestone for bone ash and AID. Ca and Pi levels were the most influential factors in determining bone ash although phytase inclusion could lead to an improvement during early days.

Effects of calcium carbonate, magnesium oxide and encapsulated sodium bicarbonate on measures of post-ruminal fermentation.

Evidence suggests that lipopolysaccharide (LPS) absorbed from the large intestine may contribute to the inflammatory response to high starch feeding in dairy cows. This work evaluated the impact of buffers or alkalinizing agents with expected large intestinal activity on faecal indicators of intestinal fermentation and LPS. Ten late-lactation cows were used in a replicated 5 × 5 Latin square design with 7-day periods. Cows were fed a diet containing 265 g/kg dry matter of starch and were abomasally infused with 1 g/kg body weight cornstarch daily. Treatments were control (CON), ration supplementation with 200 g/day sodium bicarbonate (FSB), 200 g/day calcium carbonate (FCC) or 125 g/day calcium carbonate plus 75 g/day of magnesium oxide (FCCM), or abomasal infusion of a lipid encapsulate providing 200 g/day sodium bicarbonate (ISB). The FCC, FCCM and ISB treatments were hypothesized to have large intestinal buffering effects, and FSB was included as a secondary control. Milk, feed, rumen and faecal samples were collected on day 7 of each period. Treatment did not affect intake, milk yield or milk composition. There were no effects of treatment on ruminal measures except that ISB tended to reduce and the post-ruminal treatments as a whole (FCC, FCCM and ISB) reduced rumen butyrate compared with CON. Faecal pH was greater for FCCM compared with all other treatments. Total faecal VFA tended to increase with FCC and FCCM compared with CON and was increased by the post-ruminal treatments as a whole compared with CON. Treatment did not affect faecal dry matter, lactate or LPS or apparent total tract nutrient digestibility. Although some treatments altered fermentation as evidenced by the change in faecal VFA, this was not accompanied by a decrease in faecal LPS. The strategies employed in this study had limited effects on large intestinal fermentation.

Possible roles of parathyroid hormone, 1.25(OH)2D3, and fibroblast growth factor 23 on genes controlling calcium metabolism across different tissues of the laying hen.

This study provides an integrative description of candidate gene expression across tissues involved in calcium (Ca) metabolism during the egg laying cycle, using the well-defined model of Ca supply as fine or coarse particles of calcium carbonate (CaCO3). Plasma and tissue samples were collected from hens at the peak of laying at 0 to 1, 9 to 10, and 18 to 19 h postovulation (PO). After mRNA preparation from the parathyroid gland, medullary bone, liver, kidney, duodenum, and jejunum, gene expressions were quantified using RT-qPCR. The highest levels of parathyroid hormone (PTH) mRNA in the parathyroid gland (P < 0.05), and of the active form of vitamin D3 1.25(OH)2D3 in the plasma (P < 0.01) were observed at 18 to 19 h PO. During this active phase of eggshell formation, bone resorption was attested to high levels of plasma inorganic phosphorus (iP) and the receptor activation of nuclear factor-κB expression in the bone (P < 0.001 and P < 0.05, respectively). At this stage, 5 genes of the transcellular and the paracellular Ca absorption pathways in the intestine (P < 0.05) and the Ca channel transient receptor potential cation channel subfamily V member 5 (P < 0.05), involved in its reabsorption in the kidney, were overexpressed. At 0 to 1 h PO during the subsequent daylight period, 2 candidates of the transcellular and the paracellular Ca pathways (P < 0.05) remained at high levels in the intestine, while calbindin D 28K expression was the highest in the kidney (P < 0.05). As PTH mRNA and 1.25(OH)2D3 were low, bone accretion was likely active at this stage. The phosphaturic hormone fibroblast growth factor 23 (FGF23) was overexpressed at 18 to 19 h PO (P < 0.05) in the bone when plasma iP was high, which suggested a role in the subsequent reduction of P reabsorption in the kidney, as attested to the decreased expression of P cotransporters, leading to iP clearance from the plasma at 0 to 1 h PO (P < 0.05). The low levels of 1.25(OH)2D3 at this stage coincided with increased expression of the 24-hydroxylase gene in the kidney (P < 0.05). In hens fed fine particles of CaCO3, higher plasma levels of 1,25(OH)2D3 and higher expression of several genes involved in bone turnover reflected a stronger challenge to Ca homeostasis. Altogether, these data support the hypothesis that FGF23 could drive vitamin D metabolism in the laying hen, as previously documented in other species and explain the tight link between P and Ca metabolisms.