Milk-Alkali Syndrome: A Century-old Cause of Hypercalcemia Requires the Addition of Venous Blood Gas in Hypercalcemia Workup.

The Milk-Alkali syndrome (MAS) is identified by the triad of high serum levels of calcium, metabolic alkalosis, and acute kidney injury, usually caused by consuming excessive amounts of calcium and absorbable alkali. If not treated promptly, the syndrome can result in rapid hypercalcemia, acute renal failure, and metastatic calcification. Notably, an increasing number of cases of MAS have been observed, potentially due to the rampant use of calcium-based over-the-counter supplements for the prevention and treatment of osteoporosis in postmenopausal women. Herein, we report a case of severe hypercalcemia due to prolonged intake of calcium carbonate supplements in the absence of any alkali. The case report highlights the importance of including venous blood gas (VBG) analysis as a part of the workup for hypercalcemia, as metabolic alkalosis can help clinch the diagnosis of MAS in the setting of severe hypercalcemia. How to cite this article: Sahu U, Trivedi T, Gupta R. Milk-Alkali Syndrome: A Century-old Cause of Hypercalcemia Requires the Addition of Venous Blood Gas in Hypercalcemia Workup. J Assoc Physicians India 2023;71(9):104-105.

Relative bioavailability and pharmacokinetic comparison of calcium glucoheptonate with calcium carbonate.

Adequate calcium intake is important for the prevention of bone loss and osteoporosis. For some populations such as those of Southeast Asia where calcium intake is very low, supplements represent a suitable dietary source of calcium. The objective of this study was to compare the relative oral bioavailability of calcium from calcium glucoheptonate, a highly soluble calcium salt containing 8.2% of elemental calcium, to that of calcium carbonate. A single-dose, randomized-sequence, open-label, two-period crossover study, with a 7-day washout period, was conducted in 24 Indonesian healthy adult volunteers. After a 12-hour (overnight) fast, subjects received either two oral ampoules of 250 mg/10 mL of calcium glucoheptonate each or one effervescent tablet of calcium carbonate containing 500 mg of elemental calcium. The relative oral bioavailability of calcium from calcium glucoheptonate as compared to calcium carbonate was 92% within 6 hours and 89% within 12 hours after study drug administration. The 90% confidence intervals for the mean test/reference ratios of the maximum plasma concentration and the area under the concentration-time curve at 12 hours post-administration were 77.09%-120.31% and 60.58%-122.30%, respectively. Five subjects experienced a total of eight adverse events which were all mild and transient; no serious adverse events or deaths were reported. These results indicate that calcium glucoheptonate is associated with a high relative bioavailability of calcium compared to calcium carbonate, and is well-tolerated. Calcium glucoheptonate might thus be a potential choice for calcium supplementation in Southeast Asian populations.

Comparison of the effects of lanthanum carbonate and calcium carbonate on the progression of cardiac valvular calcification after initiation of hemodialysis.

BACKGROUND: Although mineral metabolism disorder influences cardiac valvular calcification (CVC), few previous studies have examined the effects of non-calcium-containing and calcium-containing phosphate binders on CVC in maintenance hemodialysis patients. The aim of the present study was to compare the effects of lanthanum carbonate (LC) with calcium carbonate (CC) on the progression of CVC in patients who initiated maintenance hemodialysis and to investigate clinical factors related to CVC. METHODS: The current study included 50 subjects (mean age 65 years, 72% males) from our previous randomized controlled trial (LC group, N = 24; CC group, N = 26). CVC was evaluated as CVC score (CVCS) using echocardiography at baseline and 18 months after initiation of hemodialysis. We compared CVCS and the changes between the two groups. We also analyzed the associations between CVCS and any other clinical factors including arterial plaque score (PS) and serum phosphorus levels. RESULTS: Baseline characteristics of study participants including CVCS were almost comparable between the two groups. At 18 months, there were no significant differences in mineral metabolic markers or CVCS between the two groups, and CVCS were significantly correlated with PS (r = 0.39, p < 0.01). Furthermore, changes in CVCS were significantly correlated with average phosphorus levels (r = 0.36, p < 0.05), which were significantly higher in high serum phosphorus and high PS group compared to low serum phosphorus and low PS group (p < 0.05). CONCLUSIONS: In the present study, there were no significant differences between LC and CC with regard to progression of CVC. However, serum phosphorus levels and arterial plaque seem to be important for the progression and formation of CVC in hemodialysis patients.

Iron Deficiency Anemia Associated With Acid-Modifying Medications: Two Cases and Literature Review.

Iron deficiency anemia is often listed among potential adverse effects of gastric acid-suppressive medications, given that gastric acidity promotes intestinal absorption of nonheme iron. Additionally, the antacid calcium carbonate can inhibit iron absorption. However, there is little direct clinical evidence that proton-pump inhibitors, histamine-2 receptor antagonists, or calcium carbonate cause iron deficiency anemia. Most case reports have had substantial limitations (e.g., minimal follow-up and presence of other causes of iron deficiency), and retrospective cohort studies have lacked sufficient patient-specific detail to make strong causal inferences. We present 2 cases-both with detailed, prospective 10-year follow-up-in which combinations of proton-pump inhibitors, histamine-2 receptor antagonists and calcium carbonate were clearly associated with development of iron deficiency anemia. Overt iron-deficiency anemia is probably uncommon in patients who use acid-modifying medications and who have no other conditions that predispose to iron deficiency. Nevertheless, clinicians should be aware of this potential complication, given widespread use of these agents.

Prevalence and pattern of potential drug-drug interactions among chronic kidney disease patients in south-western Nigeria.

BACKGROUND: Management of chronic kidney disease (CKD) patients often requires the use of multiple drugs due to a high number of cardiovascular risk factors and complications associated with the disease. Multiple drugs predispose to potential drug-drug interactions (DDIs) which may be associated with increased morbidity, mortality, length of hospital stay and health-care cost. OBJECTIVES: This study determined the prevalence and pattern of potential DDIs among CKD patients attending Kidney Care Centre, in Ondo City, Nigeria. METHODOLOGY: It was an 18-month retrospective study that involved the reviewed CKD patients' records. The Lexi-Interact database was used to evaluate patients' medications for potential DDIs. RESULTS: One hundred and twenty-three (123) CKD patients, made up of 82 (66.67%) males and 41 (33.33%) females were studied. The mean age of the CKD patients was 53.81 ± 16.03 years. The most common comorbid conditions were hypertension in 103 (83.74%) and diabetes mellitus in 39 (31.71%). A total of 1237 prescriptions were made and the mean number of prescribed medications per patient was 10.06 ± 3.97. A total number of 1851 potential DDIs were observed among 118 patients. The prevalence of potential DDIs was 95.9% while the mean DDIs per prescription was 1.27. Among the potential DDIs observed, the severity was mild in 639 (34.5%), moderate in 1160 (62.7%), major in 51 (2.8%) and only 1 (0.1%) was of avoid drug combination. The most frequent DDI was between calcium carbonate and oral ferrous sulphate. CONCLUSION: The prevalence of potential DDIs is high among CKD patients. About 63% of these interactions have moderate severity. Clinicians and pharmacists should utilise available DDI software to avoid harmful DDIs in CKD patients.

Effect of calcium carbonate particle shape on phagocytosis and pro-inflammatory response in differentiated THP-1 macrophages.

Phagocytosis is a physiological process used by immune cells such as macrophages to actively ingest and destroy foreign pathogens and particles. It is the cellular process that leads to the failure of drug delivery carriers because the drug carriers are cleared by immune cells before reaching their target. Therefore, clarifying the mechanism of particle phagocytosis would have a significant implication for both fundamental understanding and biomedical engineering. As far as we know, the effect of particle shape on biological response has not been fully investigated. In the present study, we investigated the particle shape-dependent cellular uptake and biological response of differentiated THP-1 macrophages by using calcium carbonate (CaCO3)-based particles as a model. Transmission electron microscopy analysis revealed that the high uptake of needle-shaped CaCO3 particles by THP-1 macrophages because of their high phagocytic activity. In addition, the THP-1 macrophages exposed to needle-shaped CaCO3 accumulated a large amount of calcium in the intracellular matrix. The enhanced release of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) by the THP-1 macrophages suggested that the needle-shaped CaCO3 particles trigger a pro-inflammatory response. In contrast, no pro-inflammatory response was induced in undifferentiated THP-1 monocytes exposed to either needle- or cuboidal-shaped CaCO3 particles, probably because of their low phagocytic activity. We also found that phosphate-coated particles efficiently repressed cellular uptake and the resulting pro-inflammatory response in both THP-1 macrophages and primary peritoneal macrophages. Our results indicate that the pro-inflammatory response of macrophages upon exposure to CaCO3 particles is shape- and surface property-dependent, and is mediated by the intracellular accumulation of calcium ions released from phagocytosed CaCO3 particles.

Antacid abuse: a rare cause of severe hypercalcaemia.

We discuss a case of an 81-year-old man who presented to hospital with a case of severe hypercalcaemia (5.07 mmol/L). The two most common causes of hypercalcaemia, making up around 90% of the cases, are malignancy and primary hyperparathyroidism. Initial investigations are guided by this knowledge. In this case, no underlying malignancy or evidence of a parathyroid adenoma causing primary hyperparathyroidism was found. Instead, on further history, it was found that this patient had troublesome dyspepsia symptoms for which he had ingested 10-12 calcium carbonate tablets a day for the preceding 2 years. This amounts to 6.6-7.9 g of calcium carbonate per day compared with the guideline daily intake of calcium of 1 g. His presentation of severe hypercalcaemia was therefore diagnosed as milk-alkali syndrome secondary to calcium carbonate tablet abuse.

Trace Elemental Characterization of Chalk Dust and Their Associated Health Risk Assessment.

It is evident that chalk produces dust on use, i.e., particulate matter, which will alter the air quality of classrooms and can cause health hazards in teachers. The possible causes for health effects of chalk dust on teachers are still unclear. Hence, the aim of this study is to estimate the concentration of trace elements (Al, Cr, Mn, Fe, Co, Ni, Si, Pb) in chalk dust collected from classrooms by using ICP-MS. Both suspended and settled chalk dust was collected from selected classrooms. Suspended chalk dust was collected with PM2.5 filter paper using fine dust sampler, and settled chalk dust was collected by placing petriplates at a distance of 3 m from the board for a duration period of 30 min. Scanning electron microscopy images of chalk dust were taken up. Potential health risk analysis was also assessed. Results showed that Al, Fe, and Mn are in higher concentration (>1000 µg kg-1) in both settled and suspended chalk dust. Cr, Mn, Fe, Co, and Ni were beyond the minimal risk levels in both settled and suspended chalk dust. There are no minimal risk levels for the elements Al, Si, and Pb. The concentration of trace elements in suspended chalk dust was higher than that in settled chalk dust. The SEM images of PM2.5 filter papers (suspended chalk dust) showed that all pores of the sampled filter papers are clogged with chalk dust. The few SEM images of the settled chalk dust showed fibrous shape which is associated with good-quality chalk whereas others showed circular and more aggregated nature of chalk dust from low-quality chalk from which the dust production will be very high. As observed from the result that the trace elements concentration was high in the suspended chalk dust, the fact can be correlated with the SEM images which have shown high density of absorbed chalk dust. With reference to human health risk, dermal exposure was the main route of exposure followed by inhalation and ingestion. Al (aluminum), Fe (iron), Si (silicon), and Mn (manganese) are the major contributors for the non-carcinogenic effects. For all the elements, the carcinogenic effect calculated (LADD) is within the global acceptable limit (10-6-10-4).

Effect of metal-cation antacids on the pharmacokinetics of 1200 mg raltegravir.

OBJECTIVES: Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once-daily regimen (QD) at a dose of 1200 mg is under development. The effect of calcium carbonate and magnesium/aluminium hydroxide antacids on the pharmacokinetics of a 1200 mg dose of raltegravir was assessed in this study. METHODS: An open-label, four-period, four-treatment, fixed-sequence study in 20 HIV-infected patients was performed. Patients needed to be on raltegravir as part of a stable treatment regimen for HIV, and upon entry into the trial received 5 days of 1200 mg raltegravir as pretreatment, before they entered the four-period study: 1200 mg of raltegravir alone (period 1), calcium carbonate antacid as TUMS® Ultra Strength (US) 1000 and 1200 mg raltegravir given concomitantly (Period 2), magnesium/aluminium hydroxide antacid as 20 ml MAALOX® Maximum Strength substitute MS given 12 h after administration of 1200 mg raltegravir (period 3), and calcium carbonate antacid as TUMS® US 1000 given 12 h after administration of 1200 mg raltegravir (period 4). Patients received their dose of 1200 mg QD raltegravir during the intervals between periods to re-establish steady state. AUC0-24 , C24 , Cmax and Tmax were calculated from the individual plasma concentrations of 1200 mg QD raltegravir after administration alone or with a calcium carbonate antacid or with a staggered dose of a calcium carbonate antacid or magnesium/aluminium hydroxide antacid. Adverse events, in addition to laboratory safety tests (haematology, serum chemistry and urinalysis), 12-lead electrocardiograms and vital signs were assessed. KEY FINDINGS: All treatments were well tolerated in the study. Metal-cation antacids variably affected the pharmacokinetics of 1200 mg QD raltegravir. When calcium carbonate antacid was given with 1200 mg raltegravir concomitantly, the geometric mean ratio (GMR) and its associated 90% confidence interval (90% CI) for AUC0-24 , Cmax and C24 h were 0.28 (0.24, 0.32), 0.26 (0.21, 0.32) and 0.52 (0.45, 0.61), respectively. When calcium carbonate antacid and magnesium/aluminium hydroxide were given 12 h after raltegravir 1200 mg QD dosing, the GMR (90% CI) values for AUC0-24 and Cmax were 0.90 (0.80, 1.03), 0.98 (0.81, 1.17), and 0.86 (0.73, 1.03), 0.86 (0.65, 1.15), respectively. However, significant reduction in the trough concentrations of raltegravir was observed: C24 h 0.43 (0.36, 0.51) in the presence of calcium carbonate antacids and 0.42 (0.34, 0.52) in presence of magnesium/aluminium hydroxide, respectively. CONCLUSIONS: Overall, the use of metal-cation antacids with 1200 mg QD raltegravir is not recommended.

Evaluation of potential drug- drug interactions among Palestinian hemodialysis patients.

BACKGROUND: The aims of this study are to find the prevalence of potential drug-drug interactions (DDIs) in patients with Hemodialysis and identify factors associated with these interactions if present. METHODS: The study was an observational- retrospective cohort study that was conducted in ten hemodialysis units in the West bank, Palestine, between June and August 2015. The data collection form was completed by interviewing the patients in addition to reviewing their medical records. Potential DDIs were reviewed. SPSS program was used for data analysis. RESULTS: The study included 275 patients, a total of 930 potential interactions were identified in 245 (89.1 %) patients. Patients were prescribed 1-15 drugs with a mean (± SD) of 7.87 ± 2.44, calcium carbonate was the most common drug prescribed. The most common potential interaction in 114 (41.5 %) patients was Calcium Carbonate/Amlodipine followed by Calcium Carbonate/Aspirin in 76 (27.6 %) cases. Most patients (89.9 %) of the patients had one or more comorbid diseases; hypertension, diabetes and gout were the most common. Univariate analysis showed that the number of potential DDIs were related to the number of diseases, the number of prescribed drugs (P value <0.0001) and the age of the patient (P value = 0.015). The results of multiple linear regression showed a significant positive association between number of potential DDIs with the total number of medications (r = 0.242; p < 0.001). CONCLUSION: The prevalence of potential drug- drug interactions among hemodialysis patients is very common; they are highly expected and depend on the number of drugs taken by the patients. Many of these potential interactions are considered as preventable drug- related problems, so screening for potential interactions and monitoring regularly is highly needed.

Association between domestic water hardness, chlorine, and atopic dermatitis risk in early life: A population-based cross-sectional study.

BACKGROUND: Domestic water hardness and chlorine have been suggested as important risk factors for atopic dermatitis (AD). OBJECTIVE: We sought to examine the link between domestic water calcium carbonate (CaCO3) and chlorine concentrations, skin barrier dysfunction (increased transepidermal water loss), and AD in infancy. METHODS: We recruited 1303 three-month-old infants from the general population and gathered data on domestic water CaCO3 (in milligrams per liter) and chlorine (Cl2; in milligrams per liter) concentrations from local water suppliers. At enrollment, infants were examined for AD and screened for filaggrin (FLG) skin barrier gene mutation status. Transepidermal water loss was measured on unaffected forearm skin. RESULTS: CaCO3 and chlorine levels were strongly correlated. A hybrid variable of greater than and less than median levels of CaCO3 and total chlorine was constructed: a baseline group of low CaCO3/low total chlorine (CaL/ClL), high CaCO3/low total chlorine (CaH/ClL), low CaCO3/high total chlorine (CaL/ClH) and high CaCO3/high total chlorine (CaH/ClH). Visible AD was more common in all 3 groups versus the baseline group: adjusted odds ratio (AOR) of 1.87 (95% CI, 1.25-2.80; P = .002) for the CaH/ClL group, AOR of 1.46 (95% CI, 0.97-2.21; P = .07) for the CaL/ClH, and AOR of 1.61 (95% CI, 1.09-2.38; P = .02) for the CaH/ClH group. The effect estimates were greater in children carrying FLG mutations, but formal interaction testing between water quality groups and filaggrin status was not statistically significant. CONCLUSIONS: High domestic water CaCO3 levels are associated with an increased risk of AD in infancy. The influence of increased total chlorine levels remains uncertain. An intervention trial is required to see whether installation of a domestic device to decrease CaCO3 levels around the time of birth can reduce this risk.

Erasmus syndrome in a marble worker.

Erasmus syndrome is defined as the association of silica exposure and subsequent development of systemic sclerosis. The limited number of cases reported in the literature mainly involves miners and only sporadically other professionals. We describe a case of Erasmus syndrome in a marble worker. A 68 year old man came to our observation complaining pelvic and scapular girdle pain, evening fever, intense weakness and emaciation for about 1 month. He also reported to have had Raynaud's phenomenon in his hands for the last 13 years. Also, his occupational history revealed a chronic exposure to silica dust. The patient presented pain in his shoulders and hips, moderate skin thickening and sclerosis in his hands and fingers extending proximally to his wrists. The diagnosis of systemic sclerosis was determined according to his clinical and medical history, the positivity of anti-Scl 70 antibodies, the nailfold capillaroscopy suggestive of an active scleroderma pattern and the detection of a mild restrictive pulmonary syndrome. The evaluation of the organbased complications excluded a gastroenterological and cardiovascular involvement, while the chest computed tomography (CT) detected multiple small nodules with a mantle distribution and enlarged lymph nodes with no signs of interstitial lung disease and fibrosis. Additional tests (positron emission tomography-CT, flexible bronchoscopy and broncho-alveolar lavage) excluded infectious diseases and cancer. However, given the pulmonary involvement, we performed a histological examination of the parenchyma and lymph nodes, which revealed a picture of pneumoconiosis. In the end, the occupational history and the findings from the diagnostic procedures led to the diagnosis of pulmonary silicosis. The precise definition of the pulmonary involvement was essential to the therapeutic approach to this patient.

Biocompatibility of bio based calcium carbonate nanocrystals aragonite polymorph on NIH 3T3 fibroblast cell line.

BACKGROUND: Currently, there has been extensive research interest for inorganic nanocrystals such as calcium phosphate, iron oxide, silicone, carbon nanotube and layered double hydroxide as a drug delivery system especially in cancer therapy. However, toxicological screening of such particles is paramount importance before use as delivery carrier. In this study we examine the biocompatibility of CaCO3 nanocrystal on NIH 3T3 cell line. MATERIAL AND METHODS: Transmission and field emission scanning electron microscopy (TEM and FESEM) were used for the characterisation of CaCO3 nanocrystals. Cytotoxicity and genotoxic effect of calcium carbonate nanocrystals in cultured mouse embryonic fibroblast NIH 3T3 cell line using various bioassays including MTT, and Neutral red/Trypan blue double-staining assays. LDH, BrdU and reactive oxygen species were used for toxicity analysis. Cellular morphology was examined by scanning electron microscopy (SEM) and confocal fluorescence microscope. RESULTS: The outcome of the analyses revealed a clear rod-shaped aragonite polymorph of calcium carbonate nanocrystal. The analysed cytotoxic and genotoxicity of CaCO3 nanocrystal on NIH 3T3 cells using different bioassays revealed no significance differences as compared to control. A slight decrease in cell viability was noticed when the cells were exposed to higher concentrations of 200 to 400 µg/ml, while increase in ROS generation and LDH released at 200 and 400 µg/ml was observed. CONCLUSIONS: The study has shown that CaCO3 nanocrystal is biocompatible and non toxic to NIH 3T3 fibroblast cells. The analysed results offer a promising potential of CaCO3 nanocrystal for the development of intracellular drugs, genes and other macromolecule delivery systems.

Concentração de flúor em dentifrícios comercializados no Estado da Paraíba, Brasil / Fluoride Concentration in Commercial Brands of Dentifrices Available in the State of Paraíba, Brazil

Objetivo: Verificar a concentração de flúor total (FT), flúor solúvel total (FST) e flúor iônico (FI) nos dentifrícios comercializados no Estado da Paraíba e avaliar as concentrações de FST em relação à presença de ar condicionado nos estabelecimentos comerciais e em relação às normas brasileiras vigentes. Método: As amostras foram coletadas de acordo com a disponibilidade e variedade de marcas comerciais (n= 18) em 11 cidades distribuídas em todas as regiões do estado. As análises das amostras (n= 69) foram feitas em triplicata, nas quais se utilizou eletrodo específico após hidrólise do flúor ionizável em HCl, neutralização com NaOH e tamponamento com TISAB II. Os dados foram analisados através da estatística descritiva e foi utilizado o teste paramétrico ANOVA, com nível de significância de 5%. Resultados: A maioria das amostras (83,3%) possuía flúor na forma de monofluorfosfato de sódio. Em relação ao abrasivo, 72,2% apresentavam carbonato de cálcio. As concentrações (ppm) médias de FST encontradas nos dentifrícios nos grupos com e sem ar condicionado em estabelecimentos comerciais não diferiram estatisticamente (p>0,05). Observou-se que, das 18 marcas analisadas, 16 estão de acordo com as normas da ANVISA apresentando valores logo abaixo dos 1500 ppm e apenas duas amostras excederam este limite. Conclusão: Não há diferença nas concentrações de flúor entre os estabelecimentos com e sem ar condicionado, a maioria dos dentifrícios estão de acordo com as normas brasileiras da ANVISA e também conforme as informações em suas embalagens.

Objective: To assess total fluoride (TF), total soluble fluoride (TSF) and ionic fluoride (FI) concentrations in commercial brands of dentifrices available in the State of Paraíba, Brazil and to evaluate TSF concentrations in the dentifrices in air-conditioned retail stores and whether they conform to the Brazilian up-to-date regulations.Method: The samples were collected according to the availability and variety of commercial brands (n=18) in 11 cities scattered in all regions of the state of Paraíba. Sample analyses (n=69) were made in triplicate with a specific electrode after hydrolysis of the ionizable fluoride in HCl, neutralization in NaOH and buffering in TISAB II. The data were analyzed by descriptive statistics and ANOVA at a 5% significance level.Results: Most of the samples (83.3%) contained fluoride in the form of sodium monofluorphosphate. The abrasive agent was calcium carbonate in 72.2% of the samples. The mean TFS concentrations (ppm) detected in the dentifrices purchased from retail stores with and without air conditioning had no statistically significant differences (p>0.05). It was also observed that 16 out of the 18 analyzed commercial brands conformed to the ANVISA regulations, with fluorides concentration just below 1,500 ppm threshold. Only two samples exceeded this value.Conclusion: There was no statistically significant difference in fluoride concentrations in the dentifrices from air-conditioned and non air-conditioned stores; most of the dentifrices were in accordance with the Brazilian regulations and also with the information on their packages.

Calcium carbonate does not affect nilotinib pharmacokinetics in healthy volunteers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Gastric upset is a common side effect of nilotinib therapy, and calcium carbonate is frequently used concomitantly, either as antacid or as calcium supplementation. With the increasing number of oral agents in cancer therapy, oral drug-drug interactions are becoming more relevant. Nilotinib has already been shown to be absorbed to a much lesser extent when co-administered with proton pump inhibitors. Because exposure to sub-therapeutic concentrations of anticancer drugs such as nilotinib may result in selection of resistant clones and ultimately relapse, we studied the effect of a calcium carbonate supplement (Tums Ultra 1000®) on nilotinib pharmacokinetics. WHAT THIS STUDY ADDS: Calcium carbonate may be co-administered with nilotinib without significantly affecting the pharmacokinetics of nilotinib and potentially impacting efficacy. PURPOSE: Nilotinib is a second-generation oral tyrosine kinase inhibitor with superior efficacy compared with imatinib mesylate in the treatment for chronic phase chronic myelogenous leukemia. Calcium carbonate is commonly used as a source of calcium supplementation or as antacid to ameliorate the gastrointestinal side effects associated with nilotinib, which could have unknown effects on nilotinib absorption. The purpose of this study was to provide information on the effect of calcium carbonate on the PK of nilotinib in healthy volunteers. METHODS: Healthy subjects were enrolled in a two-period, open-label, single-institution, randomized, cross-over, fixed-schedule study. In one period, each subject received 400 mg of nilotinib p.o. In the other period, 4,000 mg of calcium carbonate (4 X Tums Ultra 1000®) was administered p.o. 15 min prior to the nilotinib dose. Plasma samples were collected at specified timepoints, concentrations of nilotinib were quantitated by LC-MS, and data were analyzed non-compartmentally. RESULTS: Eleven subjects were evaluable. Calcium supplementation did not significantly affect nilotinib pharmacokinetic parameters including area under the plasma concentration versus time curve (18.4 µg/mL h alone vs. 16.9 µg/mL h with calcium carbonate, p = 0.83; 80 % power); maximum plasma concentration (C(max)) (0.670 µg/mL alone vs. 6.18 µg/mL with calcium carbonate, p = 0.97); or half-life (18.9 h alone vs. 17.2 h with calcium carbonate, p = 0.18). CONCLUSIONS: Our results indicate that the use of calcium carbonate does not significantly affect nilotinib pharmacokinetics.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.

SUMMARY: The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. INTRODUCTION: This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. METHODS: WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). RESULTS: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. CONCLUSION: Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Investigating the effect of using granite and marble as a building material on the radiation exposure of humans.

The aim of this study was to comprehensively study the radiological hazards of granite and marble used as a building material in Egypt. The activity concentrations of (226)Ra, (232)Th and (40)K were determined using high-resolution hyper-pure germanium detectors in 25 samples of different types of commercially available granite and marble. The measured activity concentrations for these natural radionuclides were compared with the reported data for Egypt and other countries. In order to assess the radiological impact, the radiation hazard parameters such as radium equivalent activity (Ra(eq)) and hazard level index (I(γ)) were calculated. The internal and external dose rates due to natural radionuclides in granite and marble were also calculated. The data obtained were considered as helpful  in regulating the use of building materials in Egypt.