Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca2+-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca2+ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy. However, its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM). Here, we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate (CaCO3) biomineralized Salmonella (Sal) as an in-situ cancer vaccine producer and systematical ITM regulator. CaCO3 can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading, and such biomineralization did not affect the bioactivities of the bacteria. Upon intratumoral accumulation, the CaCO3 shell was decomposed at an acidic microenvironment to attenuate tumor acidity, accompanied by the release of Sal and Ca2+/A23187. Specifically, Sal served as a cancer vaccine producer by inducing cancer cells' immunogenic cell death (ICD) and promoting the gap junction formation between tumor cells and dendritic cells (DCs) to promote antigen presentation. Ca2+, on the other hand, was internalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system, including DCs maturation, macrophages polarization, and T cells activation. As a result, such bio-vaccine achieved remarkable efficacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility. This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.

LA DUREZA TOTAL DEL AGUA AFECTA LA MUDA, CALCIFICACIÓN, CRECIMIENTO Y SUPERVIVENCIA DE Cryphiops caementarius (PALAEMONIDAE) / The total water hardness affects molting, calcification, growth and survival of Cryphiops caementarius (Palaemonidae)

RESUMEN El objetivo de este estudio fue evaluar los efectos de diferentes niveles de dureza total del agua en la muda, calcificación del exoesqueleto, crecimiento y supervivencia de Cryphiops caementarius. Los camarones machos fueron colectados del río Pativilca (Lima, Perú) y cultivados en recipientes individuales dentro de acuarios (55 L). Se emplearon cuatro niveles de dureza total del agua (100, 200, 300 y 400 mg CaCO3 L-1), con tres repeticiones, respectivamente. Los camarones cultivados en agua con dureza de 300 mg L-1 tuvieron menor periodo de muda (26,7 días) y mayor frecuencia de mudas (tres mudas). El contenido de calcio del exoesqueleto del camarón incrementó (p < 0,05) de 25 a 31 % en agua con dureza de 100 y 400 mg L-1, respectivamente. El mayor grosor del exoesqueleto (144 -jm en cefalotórax y 131 μm en abdomen) fue obtenido en agua con dureza de 400 mg L-1 y el menor grosor (93 -jm en cefalotórax y abdomen) en 100 mg L-1. El crecimiento en longitud fue mayor (p < 0,05) en agua con durezas de 200 y 300 mg L-1. El crecimiento en peso fue similar (p > 0,05) entre tratamientos. La mayor supervivencia (> 94,4 %) se mantuvo en agua con durezas de hasta 300 mg L-1 y la menor supervivencia (77,8 %) fue con 400 mg L-1. La dureza total del agua de 200 y 300 mg L-1 es conveniente para el cultivo del camarón, pero dureza del agua mayor o menor a este rango afectan la muda, el crecimiento y la supervivencia por deficiencia o exceso de calcio acumulado, respectivamente en el exoesqueleto del camarón.

ABSTRACT The aim of this work was to evaluate the effects of different levels of total hardness on the molting, calcification of exoskeleton, growth and survival of Cryphiops caementarius prawn. Male prawns were collected from Pativilca river (Lima, Peru) and cultivated in individual containers inside aquariums (55 L). Four levels of the total hardness of water (100, 200, 300 and 400 mg CaCO3 L-1) were used, with three repetitions, respectively. Prawns cultured in water with hardness of 300 mg L-1 has a shorter molting period (26.7 days) and a higher frequency of molts (three molts). The calcium content of the prawn exoskeleton increased (p < 0.05) from 25 to 31 % in water with hardness of 100 and 400 mg L-1, respectively. The greatest thickness of the exoskeleton (144 -jm cephalothorax and 131 -jm abdomen) was obtained in water with a hardness of400 mg L-1 and the smallest thickness (93 -jm in the cephalothorax and abdomen) in 100 mg L-1. The growth in length was greater (p < 0.05) in water with hardness of 200 and 300 mg L-1. The weight growth was similar (p > 0.05) between treatments. The highest survival (> 94.4 %) was maintained in water with hardness up to 300 mg L-1 and the lowest survival (77.8 %) was at 400 mg L-1. The total hardness of 200 and 300 mg L-1 is suitable for prawn farming, but hardness high or lower than this range affects the molting, growth and survival due to deficiency or excess of accumulated calcium, respectively, in the prawn exoskeleton.

Advances of enzymes related to microbial cement / 生物工程学报

Microbial induced calcium carbonate precipitation (MICP) refers to the natural biological process of calcium carbonate precipitation induced by microbial metabolism in its surrounding environment. Based on the principles of MICP, microbial cement has been developed and has received widespread attention in the field of biology, civil engineering, and environment owing to the merits of environmental friendliness and economic competence. Urease and carbonic anhydrase are the key enzymes closely related to microbial cement. This review summarizes the genes, protein structures, regulatory mechanisms, engineering strains and mutual synergistic relationship of these two enzymes. The application of bioinformatics and synthetic biology is expected to develop biocement with a wide range of environmental adaptability and high performance, and will bring the MICP research to a new height.

Hipocalcemia posterior a tiroidectomía total: Análisis de dosis para suplemento rutinario profiláctico / Hypocalcemia after total thyroidectomy: Dose analysis for routine prophylactic supplementation

Introducción. La hipocalcemia es la complicación más frecuente de la tiroidectomía. La profilaxis con calcio/calcitriol es una alternativa costo-efectiva, sencilla y expedita para disminuir esta situación, sin alterar la función paratiroidea residual. Lo que no está claro es si hay superioridad de una dosis frente a otra, por lo que el objetivo de este estudio fue evaluar el comportamiento entre diferentes esquemas de profilaxis para hipocalcemia. Métodos. Estudio de cohorte retrospectivo de adultos operados en un hospital de cuarto nivel, entre febrero de 2017 y diciembre de 2020. Se calculó la tasa de síntomas, la hipocalcemia e hipercalcemia bioquímica en el control postquirúrgico durante las siguientes dos semanas. Se hizo análisis bivariado y multivariado entre dosis de calcio/calcitriol, otros factores asociados y los desenlaces mencionados. Resultados. Se incluyeron 967 pacientes. El 10 % presentaron síntomas. No hubo diferencias significativas en el calcio sérico del control posquirúrgico entre los grupos con distintas dosis de calcio. La dosis de carbonato de calcio >3600 mg/día y el calcio en las primeras 24 horas de cirugía se asociaron a la presencia de síntomas. La dosis de calcitriol <1 mcg/día y el bocio aumentaron el riesgo de hipocalcemia bioquímica, mientras que la dosis de 1,5 mcg/día lo disminuyó. Ninguna variable evaluada se asoció a hipercalcemia bioquímica. Conclusiones. Podemos establecer que dosis altas de carbonato de calcio no se asocian con menos hipocalcemia bioquímica, lo cual está a favor de usar dosis intermedias (3600 mg/día). De forma similar, la dosis de calcitriol de 1,5 mcg/día disminuye el riesgo de este desenlace. La identificación de variables que aumentan o disminuyen el riesgo de hipocalcemia posterior a tiroidectomía, como bocio o el nivel de calcio en las primeras 24 horas para este estudio, pueden determinar ajustes individuales en la dosis rutinaria profiláctica de calcio/calcitriol.

Introduction. Hypocalcemia is the most frequent complication of thyroidectomy. Calcium/calcitriol prophylaxis is a cost-effective, simple and expeditious alternative to reduce this situation, without altering residual parathyroid function. It is not clear whether there is superiority of one dose over another, so the objective of this study was to evaluate the behavior between prophylaxis doses for hypocalcemia. Methods. Retrospective cohort study of adults operated in a fourth level hospital, between February 2017 and December 2020. The rate of symptoms, biochemical hypocalcemia and hypercalcemia was calculated in the post-surgical control during the following two weeks. Bivariate and multivariate analyses were performed between calcium/calcitriol dose, other associated factors, and the mentioned outcomes. Results. Out of the 967 patients included, 10% presented symptoms. There were no significant differences in postoperative control serum calcium between the groups with different doses of calcium. The dose of calcium carbonate > 3600 mg/day and calcium in the first 24 hours of surgery were associated with the presence of symptoms. The dose of calcitriol <1 mcg/day and goiter increased the risk of biochemical hypocalcemia, while the dose of 1.5 mcg / day decreased it. No variable evaluated was associated with biochemical hypercalcemia. Conclusion. We can establish that high doses of calcium are not less associated with biochemical hypocalcemia, which is in favor of intermediate doses (i.e. 3600mg/day). In a similar way, the calcitriol dose of 1.5mcg/day decreases the risk of this outcome. The identification of variables that increase or decrease the risk of this complication (goiter or the 24h serum calcium in this study) can decide settings in the rutinary prophylactic dose of calcium/calcitriol.

Fracture resistance of simulated immature teeth reinforced with different mineral aggregate-based materials

Abstract This study assessed the fracture resistance of simulated immature teeth reinforced with calcium aluminate cement (CAC) or mineral trioxide aggregate (MTA) containing calcium carbonate nanoparticles (nano-CaCO3). The microstructural arrangement of the cements and their chemical constitution were also evaluated. Forty-eight canines simulating immature teeth were distributed into 6 groups (n=8): Negative control - no apical plug or root canal filling; CAC - apical plug with CAC; CAC/nano-CaCO3 - apical plug with CAC+5% nano-CaCO3; MTA - apical plug with MTA; MTA/nano-CaCO3 - apical plug with MTA+5% nano-CaCO3; and Positive control - root canal filling with MTA. The fracture resistance was evaluated in a universal testing machine. Samples of the cements were analyzed under Scanning Electron Microscope (SEM) to determine their microstructural arrangement. Chemical analysis of the cements was performed by Energy Dispersive X-ray Spectroscopy (EDS). The fracture resistance of CAC/nano-CaCO3 was significantly higher than the negative control (p<0.05). There was no significant difference among the other groups (p>0.05). Both cements had a more regular microstructure with the addition of nano-CaCO3. MTA samples had more calcium available in soluble forms than CAC. The addition of nano-CaCO3 to CAC increased the fracture resistance of teeth in comparison with the non-reinforced teeth. The microstructure of both cements containing nano-CaCO3 was similar, with a more homogeneous distribution of lamellar- and prismatic-shaped crystals. MTA had more calcium available in soluble forms than CAC.

Resumo Este estudo avaliou a resistência à fratura de dentes imaturos simulados reforçados com cimento de aluminato de cálcio (CAC) ou trióxido agregado mineral (MTA) contendo nanopartículas de carbonato de cálcio (nano-CaCO3). O arranjo microestrutural dos cimentos e sua constituição química também foram avaliados. Quarenta e oito caninos simulando dentes imaturos foram distribuídos em 6 grupos (n=8): Controle negativo - sem plug apical ou obturação do canal radicular; CAC - plug apical com CAC; CAC/nano-CaCO3 - plug apical com CAC + 5% nano-CaCO3; MTA - plug apical com MTA; MTA/nano-CaCO3 - plug apical com MTA + 5% nano-CaCO3; e Controle positivo - obturação dos canais radiculares com MTA. A resistência à fratura foi avaliada em máquina universal de ensaios. Amostras dos cimentos foram analisadas em Microscópio Eletrônico de Varredura (MEV) para determinar seu arranjo microestrutural. A análise química dos cimentos foi realizada por Espectroscopia de Energia Dispersiva de Raio-X (EDS). A resistência à fratura de CAC/nano-CaCO3 foi significativamente maior do que o controle negativo (p<0,05). Não houve diferença significativa entre os outros grupos (p>0,05). Ambos os cimentos apresentaram microestrutura mais regular com a adição de nano-CaCO3. As amostras de MTA apresentaram mais cálcio disponível em formas solúveis do que CAC. A adição de nano-CaCO3 ao CAC aumentou a resistência à fratura dos dentes em comparação aos dentes não reforçados. A microestrutura de ambos os cimentos contendo nano-CaCO3 foi semelhante, com uma distribuição mais homogênea de cristais de formato lamelar e prismático. MTA apresentou mais cálcio disponível nas formas solúveis do que CAC.

Calcium supplementation and cardiovascular disease in postmenopausal women: a study in South Brazil / Suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa: um estudo no Sul do Brasil

Objective: To evaluate the link between calcium supplementa- tion and cardiovascular disease in postmenopausal women (aged 55 years or older). Methods: A standardized questionnaire was employed to collect data about calcium supplements, eart di- sease, and demographic of women attended at Primary Care in the South Region of Brazil. Generalized linear regression models were performed to evaluate the association and adjust for poten- tial confounders. Results: Overall, 1,057 women completed the questionnaire. Information about calcium supplementation was present in 1,035 questionnaires. The mean ± standard deviation of the age of participants was 67.2±7.6 years. The frequency of calcium supplementation was 18.6%. There was no association between heart failure, stroke, and ischemic heart disease and cal- cium supplementation (prevalence ratio; 95% confidence interval of 0.3; -0.9-0.4, -0.2; -0.8-0.4 and -0.5; -1.0-0.02, respectively. Con- clusions: Our study did not find an association of higher risk of cardiovascular disease in women using calcium supplementation at Primary Care in South Brazil.

Objetivo: Avaliar a ligação entre a suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa (com 55 anos ou mais). Métodos: Um questionário padronizado foi em- pregado para coletar dados sobre suplementos de cálcio, doenças cardíacas e demográficos de mulheres que frequentavam a Aten- ção Primária na Região Sul do Brasil. Modelos de regressão linear generalizada foram realizados para avaliar a associação e ajustar os potenciais fatores de confusão. Resultados: No total, 1.057 mulheres responderam ao questionário. As informações sobre su- plementação de cálcio estavam presentes em 1.035 questionários. A média ± desvio-padrão da idade dos participantes foi de 67,2 ± 7,6 anos. A frequência de suplementação de cálcio foi de 18,6%. Não houve associação entre insuficiência cardíaca, acidente vas- cular cerebral e doença cardíaca isquêmica e suplementação de cálcio (razão de prevalência; intervalo de confiança de 95% de -0,3; -0,9-0,4, -0,2; -0,8-0,4 e -0,5; -1,0-0,02, respectivamente). Con- clusão: Nosso estudo não encontrou associação de maior risco de doença cardiovascular em mulheres em uso de suplementação de cálcio na Atenção Primária no Sul do Brasil.

Experimental Studies to Define the Role of Calcium (Ca2+) and Voltage-Gated Calcium Channel Blockers (vCa-CCB) against Neurosteroid Induced Obesity

Introduction:Obesity is closely associated with various types of illness, primarily caused by more calorie intake than body burn. In adipocytes, Calcium (Ca2+) is an important second messenger involved in theregulation of many physiological functions which are essential for survival. In the present research, we have investigated the role of Ca2+ions in obesity by manipulating cytosolic Ca2+ion concentration by selective blocking/advancing the Ca2+ions through the voltage-gated calcium channels. Voltage-gated calcium channel (vCa) plays a key role in regulating intracellular and extracellular Ca2+concentration.Cytoplasmic level of Ca2+was manipulated by supplying calcium carbonateand by using vCa blockers i.e. nifedipine-(N-type-vCa-CCB) and ethosuximide (T-type, vCa-CCB).Methods:Obesity was induced by progesterone in female mice and test drugs were co-administered with progesterone whereas sibutramine was used as standard. The treatment was carried out for 28 days, during and afterthetreatment periodvarious parameters were studied viz food consumption, change in body weight and temperature, the effect on WAT (white adipose tissue, adiposity index, histology of fat pad) and fecal lipid content.Results:Calcium carbonate treated group has shown promising effects in the decrease in body weight by increasing fecal lipid content and lipolysis which was reflected by an increase in body temperature. Ethosuximide also offered significant protection by decreasing the food intake but has not shown any notable effect on fecal fat content, whereas nifedipine has not offered any protection against the obesity induced by neurosteroid.Conclusion:Calcium carbonate has significant anti-obesity activity by including thermogenesis, and increasing fecal lipid content

Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months.MATERIALS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6–12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections).RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D.CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

Comparative analysis of bile components in patients with different types of gallstones / 中华肝胆外科杂志

Objective To study the relationship among bile components and different gallstone types through comparing and analyzing gallbladder bile contents in patients with different types of gallstones.Methods A retrospective study of 542 consecutive patients with gallstones or gallbladder polyps was conducted.The stone composition type and 14 kinds of bile components from these patients were analyzed.The bile parameters consisted of potassium (K +),sodium (Na+),chlorine (Cl-),calcium (Ca2+),bicarbonate (HCO3-),magnesium (Mg2+),aspartate aminotransferase (AST),glutamyltranspeptidase (GGT),alkaline phosphatase (ALP),total bilirubin (TBIL),total bile acid (TBA),cholesterol (CHO),lactate dehydrogenase (LDH) and pH.Finally,the content of these bile components among the different types of stones and gallbladder polyps were compared.According to the composition determined by Fourier transform infrared spectroscopy (FTIR),the gallstone patients were divided into five groups.Results Compared with other groups,the content of K +,GGT,ALP,TBIL,TBA and CHO in the calcium carbonate stone group were lower (P ＜ 0.05),while the levels of C1-,HCO3-and value of PH were higher (P ＜0.05).Furthermore,CHO content in the cholesterol stone group was higher than other groups (P ＜ 0.05)except for the gallbladder polyp group (P ＞ 0.05).In addition,there was no difference in bile contents among the pigment gallstone group,mixed stone group and polyp group (P ＞ 0.05).Conclusions In gallstone patients,the bile components of patients with calcium carbonate stones is significantly different.The high cholesterol content in bile is the main feature of cholesterol stone patients,and there is no significant difference in bile composition between patients with pigment stones and mixed stones.

Hypoparathyroidism: what is the best calcium carbonate supplementation intake form? / Hipoparatireoidismo: qual é a melhor forma de ingestão de suplemento de carbonato de cálcio?

Abstract Introduction: In hypoparathyroidism, calcium supplementation using calcium carbonate is necessary for the hypocalcemia control. The best calcium carbonate intake form is unknown, be it associated with feeding, juice or in fasting. Objective: The objective was to evaluate the calcium, phosphorus and calcium × phosphorus product serum levels of hypoparathyroidism women after total thyroidectomy, following calcium carbonate intake in three different forms. Methods: A crossover study was carried out with patients presenting definitive hypoparathyroidism, assessed in different situations (fasting, with water, orange juice, breakfast with a one-week washout). Through the review of clinical data records of tertiary hospital patients from 1994 to 2010, 12 adult women (18-50 years old) were identified and diagnosed with definitive post-thyroidectomy hypoparathyroidism. The laboratory results of calcium and phosphorus serum levels dosed before and every 30 min were assessed, for 5 h, after calcium carbonate intake (elementary calcium 500 mg). Results: The maximum peak average values for calcium, phosphorus and calcium × phosphorus product were 8.63 mg/dL (water), 8.77 mg/dL (orange juice) and 8.95 mg/dL (breakfast); 4.04 mg/dL (water), 4.03 mg/dL (orange juice) and 4.12 mg/dL (breakfast); 34.3 mg2/dL2 (water), 35.8 mg2/dL2 (orange juice) and 34.5 mg2/dL2 (breakfast), respectively, and the area under the curve 2433 mg/dL min (water), 2577 mg/dL min (orange juice) and 2506 mg/dL min (breakfast), 1203 mg/dL min (water), 1052 mg/dL min (orange juice) and 1128 mg/dL min (breakfast), respectively. There was no significant difference among the three different tests (p > 0.05). Conclusion: The calcium, phosphorus and calcium × phosphorus product serum levels evolved in a similar fashion in the three calcium carbonate intake forms.

Resumo Introdução: No hipoparatireoidismo, a suplementação de cálcio com carbonato de cálcio é necessária para o controle da hipocalcemia. A melhor forma de ingestão de carbonato de cálcio ainda é desconhecida, seja concomitante com alimentação, no suco ou em jejum. Objetivo: Avaliar os níveis séricos de cálcio, fósforo e produto cálcio-fósforo em mulheres pós-tireoidectomia por hipoparatireoidismo, após a ingestão de carbonato de cálcio em três formas diferentes. Método: Foi realizado um estudo cruzado em pacientes com hipoparatireoidismo definitivo, avaliados em diferentes situações (em jejum, com água, suco de laranja, café da manhã, após washout de uma semana). A revisão dos prontuários dos pacientes de um hospital terciário de 1994 a 2010 identificou 12 mulheres adultas (18-50 anos), diagnosticadas com hipoparatireoidismo definitivo pós-tireoidectomia. Os resultados laboratoriais dos níveis séricos de cálcio e fósforo foram mensurados antes e a cada 30 minutos durante 5 horas, após a ingestão de carbonato de cálcio (cálcio elementar 500 mg). Resultados: Os valores de pico máximo médio de cálcio, fósforo e produto cálcio-fósforo foram 8,63 mg/dL (água), 8,77 mg/dL (suco de laranja) e 8,95 mg/dL (café da manhã); 4,04 mg/dL (água), 4,03 mg/dL (suco de laranja) e 4,12 mg/dL (café da manhã); 34,3 mg2/dL2 (água), 35,8 mg2/dL2 (suco de laranja) e 34,5 mg2/dL2 (café da manhã), respectivamente, e a área sob a curva foi 2.433 mg/dL.min. (água), 2.577 mg/dL.min. (suco de laranja) e 2.506 mg/dL.min. (café da manhã), 1.203 mg/dL.min. (água), 1.052 mg/dL.min. (suco de laranja) e 1.128 mg/dL.min. (café da manhã), respectivamente. Não houve diferença significante entre os três diferentes testes (p > 0,05). Conclusão: Os níveis séricos de cálcio, fósforo e produto cálcio-fósforo evoluíram de forma semelhante nas três formas de ingestão de carbonato de cálcio.

Study on efficacy network of Chaihu Guizhi Ganjiang Decoction in treating insomnia / 中草药

Objective: To investigate the mechanisms of effects of Chaihu Guizhi Ganjiang Decoction in the treatment of insomnia by using network pharmacology methods. Methods: TCMSP and TCMID were used to lock the targets of seven herbs in Chaihu Guizhi Ganjiang Decoction. TTD, DrugBank, and PubMed were used to search targets of insomnia and construct a “disease-prescription-target” network. STRING and Cytoscape were used to perform enrichment analysis and clarify the mechanism of core targets in the network. Results: The PPI network of Chaihu Guizhi Ganjiang Decoction contained 640 targets and the PPI network of insomnia included 175 targets. A total of 29 core targets and 80 interactions were found after enrichment analysis between two PPI networks. After GO enrichment analysis and KEGG pathway analysis of 29 key targets, we found that 171 active ingredients in Chaihu Guizhi Ganjiang Decoction such as saikosaponin a, saikosaponin d, quercetin, calcium carbonate, 6-gingerol, kaempferol, and wogonin, which played a role in the treatment of insomnia mainly through 29 core targets such as CACNA1C, GABRA1, GABRA2, GABRB3, GABRA3, with biological processes such as target and synaptic signaling, regulation of membrane potential, G-protein coupled receptor signaling pathway, and molecular functions such as neurotransmitter receptor activity, ion-gated channel activity, GABA-A receptor activity, and functional pathways composed by plasmalemma, synapse, and other cells such as neural active ligand-receptor interaction, retrograde endogenous cannabinoid signal transduction, and serotoninergic synapses. Conclusion: The pharmacological substance basis for the treatment of insomnia was composed of 171 active ingredients such as saikosaponin a and saikosaponin d. The efficacy network of “soothing liver and invigorating spleen, regulating yin and yang” was constituted by several pathways like the neural active ligand-receptor interaction and 29 targets such as CACNA1C. Our results provide network pharmacological evidence for clinical rational use of Chaihu Guizhi Ganjiang Decoction for insomnia.

Acute toxicity of cockle shell-derived calcium carbonate nanoparticles on rats / 吉林大学学报(医学版)

Objective: To observe the toxic effects of cockle shell-derived calcium carbonate nanoparticles (CCNPs) on the SD rats, and to preliminarily explore the safe dose and biological effects of CCNPs. Methods: A total of 40 healthy male SD rats were randomly divided into control group, low, middle and high doses of CCNPs groups (given 0, 30, 60, and 120 mg middot; kg-1 CCNPs). The injection was consecutively given through the lateral tail vein once per day for 14 d. The body weights and daily feed intakes of the rats in various groups were measured. The haematology indexes, serum biochemical indexes, relative weights of organs and histopathology of main organs of the rats in various groups were detected. Results: In the 14-day repeated dose toxicity experiment, two rats died in high dose of CCNPs group, while no rats died in low and middle doses of CCNPs groups. The body weights and daily average intakes of the rats in different doses of CCNPs groups were slightly lower than those in control group, but the differences were not statistically significant (P>0. 05). There were no significant differences in the serum indexes of the rats between different doses of CCNPs groups and control group (P>0. 05). Compared with control group, the relative weights of lung of the rats in different doses of CCNPs groups were increased significant (P0. 05). The histopathological analysis results showed that the mild inflammatory infiltration was found in some organs of the rats in low dose of CCNPs group, while no obviously pathological changes were found. The obviously histopathological changes were observed in the main organs of the rats in middle and high doses of CCNPs groups, including inflammatory cell infiltration, slight disorder of hepatocytes arrangement, increased vacuoles in hepatocytes; thickening of alveolar interstitium and formation of granulomas in the lung tissue; swelling, rupture and even necrosis of cardiac muscle fibers; atrophy and fissures of glomerulus and so on. Conclusion: Intravenous administration of low dose of CCNPs couldn' t cause sever acute toxicity reaction.

Muscle strength training is better than the use of growth hormone (GH) in bone health of Wistar rats / Entrenamiento de la fuerza muscular es mejor que el uso de la hormona del crecimiento (GH) en salud ósea del ratas Wistar

SUMMARY: The objective of this study was to evaluate the effects of growth hormone (GH) and muscle strength training (ST) on the composition of bone tissue of Wistar rats through Raman spectroscopy. In total, 40 male rats were randomly distributed into four groups: (N = 10) control (C), control with the application of GH (GHC), strength training (T), and strength training with the application of GH (GHT). The training consisted of four series of 10 water jumps, performed three times a week, with an overload corresponding to 50 % of body weight and duration of four weeks. GH was applied at a dose of 0.2 IU / kg in each animal three times a week and every other day. After four weeks, the animals were euthanized and the right femurs collected for analysis of the bone structure. Raman spectroscopy (ER) was used to observe the following compounds from their respective bands: Calcium Carbonate-Triglycerides (fatty acids) 1073 cm-1, Collagen type I 509 cm-1, Bone-DNA Phosphate (Protein) 589 cm-1, Phosphate Phospholipids 1078 cm-1. For the statistical analysis, the Shapiro-Wilk and ANOVA One-Way variance analysis normality tests were performed, followed by the Tukey post-test. The results showed an increase in the concentrations of calcium carbonate-triglycerides (fatty acids), type I collagen, bone phosphate-DNA (protein), and phosphate phospholipids in all experimental groups, with or without ST and/or GH , But only the isolated training group differed significantly from the control group (P <0.05). It was concluded that all treatments could promote bone tissue gain, however, only the T group demonstrated a significant difference in the mineral compounds analyzed.

RESUMEN: El objetivo del estudio fue avaluar el efecto de la aplicación de la hormona del crecimiento (GH) y entrenamiento de la fuerza muscular (EF) en la composición del tejido óseo de ratas Wistar a partir de la espectroscopía Raman. Fueron utilizadas 40 ratas machos distribuidas de forma aleatoria en cuatro grupos (n=10): control (C), control y aplicación de GH (GHC), entrenamiento de la fuerza muscular (EF) y entrenamiento de la fuerza muscular y aplicación del GH (GHE). El entrenamiento fue consistió en cuatro series de 10 saltos acuáticos, realizados tres veces en la semana, con sobrecarga correspondiente a 50 % de la masa corporal y durante cuatro semanas. El GH fue aplicado en la dosificación de 0,2 UI/kg en cada animal, tres veces en la semana y en días alternados. Después de cuatro semanas, los animales fueran eutanasiados y retirados los fémures derechos para un análisis de la estructura ósea. La espectroscopía Raman fue utilizada para observar los siguientes compuestos a partir de las respectivas bandas: Carbonato de Calcio-Triglicéridos (ácidos grasos) 1073 cm-1, Colágeno Tipo I 509 cm-1, Fosfato Óseo-DNA (Proteína) 589 cm1, Fosfato Fosfolípidos 1078 cm-1. Para el análisis estadístico, fueron realizadas las pruebas Shapiro-Wilk y el análisis de variancia ANOVA One-Way, seguida de test post hoc de Tukey. Los resultados revelaran aumento de la concentración de Carbonato de Calcio-Triglicéridos (ácidos grasos), Colágeno Tipo I, Fosfato Óseo- DNA (Proteína), Fosfato Fosfolípidos en todos los grupos experimentales, asociados o no a la realización del EF y/o aplicación del GH. Además, solamente el grupo EF mostró diferencia significativa del grupo C (p<0,05). Es posible concluir que todos los tratamientos mostraran aumentos en el tejido óseo, sin embargo, solamente el grupo T demostró una diferencia significativa en los compuestos minerales analizados.

Effect of calcium sources in the diets of adult cats on urinary parameters and acid-base balance / Efeitos das fontes de cálcio na dieta de gatos adultos sobre parâmetros urinários e equilíbrio ácido-básico

Calcium is a macroelement that is part of the mineral composition of the diet of companion animals, and is considered a cation of strong alkalizing power, increasing urinary pH. Calcium salts have different solubilities and depending on the anion to which calcium is associated with, it can be more or less absorbed, modifying the pH of the urine. The aim of this study was to evaluate the efficiency of calcium sources on alkalinization of urinary pH, as well as excretion of urinary electrolytes and acid-base balance of adult cats. An extruded diet for cats was selected, and had 160mEq/kg of calcium from the sources of either calcium carbonate (CaCO3) or calcium gluconate (C12H22CaO14) added. In the control treatment there was no addition of calcium sources, resulting in three treatments. Nine adult cats were used, mixed breed, in two experimental periods, with six replicates per treatment. Animal average age was 4±1.3 years old and average weight was 3.96±0.71kg. The cats remained in metabolic cages for an adaptation period of seven days, followed by six days of urine total collection, with volume, density, pH and calcium concentration (g/d) measurements. The acid-base balance was studied by blood gas analysis of venous blood. The two sources of calcium alkalinized the urine (P<0.001). However, calcium gluconate had less alkalinization power compared to the calcium carbonate (P<0.05). Urinary calcium was not affected by treatments, and represented less than 0.5% of calcium intake. The experiment showed that calcium, although an alkaline cation and considered strong influencer of the EB of the diet, cannot be evaluated individually, because depending on its associated anion it may have greater or lesser influence on cats urine pH.(AU)

O cálcio (Ca) é um macroelemento que faz parte da composição mineral da dieta de animais de companhia. Este macroelemento é considerado um cátion de forte capacidade alcalinizante e, de acordo com a fonte e quantidade inclusa, pode aumentar o pH urinário. Os sais de cálcio têm diferentes solubilidades e dependendo do ânion ao qual o cálcio está associado, pode ser mais ou menos absorvido e assim, alterar o pH da urina. O objetivo deste estudo foi avaliar os efeitos de duas fontes de cálcio na alcalinização do pH urinário, bem como a excreção de eletrólitos urinários e o equilíbrio ácido-básico de felinos. Foi selecionada uma dieta extrusada para gatos e adicionados 160mEq/kg de cálcio das fontes carbonato de cálcio (CaCO3) ou gluconato de cálcio (C12H22CaO14). No tratamento controle, não houve adição de fontes de cálcio. Foram utilizados nove gatos adultos, de raças mistas, em dois períodos experimentais, com seis repetições por tratamento. Os animais apresentavam idade média de 4,0±1,3 anos e peso corporal médio de 3,96±0,71kg. Estes permaneceram em gaiolas metabólicas em período de adaptação durante sete dias, seguido de coleta total de urina durante seis dias. Nestas amostras foram aferidos o volume, densidade, pH e concentração de cálcio (g/d). O equilíbrio ácido-básico foi avaliado por hemogasometria em amostras de sangue venoso. As duas fontes de cálcio alcalinizaram a urina (P<0,001). No entanto, o gluconato de cálcio apresentou menor potencial de alcalinização em comparação ao carbonato de cálcio (P<0,05). O cálcio urinário não foi afetado pelos tratamentos e representou menos de 0,5% da ingestão de Ca. O experimento demonstrou que o cálcio, apesar de ser um cátion alcalinizante e influenciador do EB da dieta, não pode ser avaliado individualmente, porque dependendo do ânion associado, pode apresentar maior ou menor influência no pH da urina de gatos.(AU)

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

Potential of Calcium Carbonate Nanoparticles for Therapeutic Applications

@#The application of nanoparticles (NPs) has attracted considerable attention as targeted delivery systems. CaCO3 has become the focus due to its advantages including affordability, low toxicity, biocompatibility, cytocompatibility, pH sensitivity and sedate biodegradability and environment friendly materials. In this article, we will discuss the potential roles of CaCO3-NPs in three major therapeutic applications; as antimicrobial, for drug delivery, and as gene delivery nanocarrier.

Calcium carbonate supplementation causes memory impairment in mice

Objective:To investigate the influence of calcium carbonate supplementation on cognitive function in mice.Methods:Mice were fed diets containing 1.0% calcium carbonate for 8 weeks, following which they were evaluated for memory function using object recognition, Y-maze, and Barnes maze tests. Next, the expression levels of cAMP response element binding protein (CREB) and phosphorylated CREB, which is involved in the memory process were investigated in both the hippocampus and cerebral cortex using western blotting methods.Results:Mice fed on a diet containing calcium carbonate showed memory impairments in object recognition, Y-maze, and Barnes maze tests with respect to the mice that were on a control diet. Further, mice that were fed a diet containing calcium carbonate and a nimodipine (an L-type calcium channel antagonist), reversed calcium carbonate-induced memory impairments, thus suggesting that excessive entry of calcium in cells may cause memory impairments. A study using western blot revealed that expression of CREB and phosphorylated CREB in hippocampus and cerebral cortex was significantly lower in the calcium carbonate-fed mice than in the control-diet-fed mice.Conclusions:These results suggest that a calcium carbonate diet may cause memory impairment by decreasing CREB expression. This is the first report of calcium carbonate supplementation causing memory impairment. This simple animal model may be useful as a novel cognitive impairment model for drug development.

Calcium carbonate supplementation causes memory impairment in mice

Objective: To investigate the influence of calcium carbonate supplementation on cognitive function in mice. Methods: Mice were fed diets containing 1.0% calcium carbonate for 8 weeks, following which they were evaluated for memory function using object recognition, Y-maze, and Barnes maze tests. Next, the expression levels of cAMP response element binding protein (CREB) and phosphorylated CREB, which is involved in the memory process were investigated in both the hippocampus and cerebral cortex using western blotting methods. Results: Mice fed on a diet containing calcium carbonate showed memory impairments in object recognition, Y-maze, and Barnes maze tests with respect to the mice that were on a control diet. Further, mice that were fed a diet containing calcium carbonate and a nimodipine (an L-type calcium channel antagonist), reversed calcium carbonate-induced memory impairments, thus suggesting that excessive entry of calcium in cells may cause memory impairments. A study using western blot revealed that expression of CREB and phosphorylated CREB in hippocampus and cerebral cortex was significantly lower in the calcium carbonate-fed mice than in the control-diet-fed mice. Conclusions: These results suggest that a calcium carbonate diet may cause memory impairment by decreasing CREB expression. This is the first report of calcium carbonate supplementation causing memory impairment. This simple animal model may be useful as a novel cognitive impairment model for drug development.

Factores asociados a la toma de suplementos de calcio en gestantes en la ciudad de Huancayo, 2018 / Factors associated with taking calcium supplements in pregnant women in Huancayo city, 2018

RESUMEN Introducción: La suplementación durante la gestación es recomendada en países en vías de desarrollo y con un alto índice de mortalidad materna, por ende, se puede medir su adherencia por el grado de comportamiento de una persona. Objetivo: Determinar los factores asociados a la adherencia en la toma de suplemento de calcio en gestantes de la ciudad de Huancayo. Material y Método: Se realizó un estudio transversal analítico, que se basó en la aplicación de una encuesta a las gestantes a partir de los 18 años hasta los 45 años, que radiquen en la provincia de Huancayo, que tengan hasta 20 semanas de embarazo y que acudan por lo menos a un control prenatal. Resultados: El 78,9% (135) tomaba suplementos de calcio. En el análisis multivariado, hubo una mayor frecuencia de toma de calcio a mayor edad gestacional (p=0,001), entre las que percibían que tomarlo trae beneficios (p=0,018) y en las que percibían que consumirlas tenía un alto costo (p<0,001), por el contrario, tomaron menos calcio las que tenían estudios técnicos (p=0,027), las que trabajaban (p=0,002) y las que tenían alguna discapacidad (p<0,001); ajustado por el que les hayan explicado los beneficios de tomarlas. Discusión: La gran mayoría de las encuestadas refirieron consumir calcio, así mismo, hubo muchos factores que influían de forma positiva y negativa para su mayor consumo; por lo que deberían emplearse técnicas para fomentar su ingesta en las gestantes, que consistan en explicar los beneficios de este suplemento.

ABSTRACT Introduction: Supplementation during pregnancy is recommended in developing countries that have a high maternal mortality rate, therefore the adherence can be measured by the behavior of a person Objective: The aim was to determine the factors associated with the adherence of calcium supplements intake in pregnant women from the city of Huancayo. Material and Method: A cross-sectional study was carried out based on the application of a survey to pregnant women from 18 to 45 years old, that live in the province of Huancayo, who also have up to 20 weeks of pregnancy and attended at least one prenatal checkup Results: 78.9% (135) took calcium supplements. In the multivariate analysis, there was a higher frequency of calcium intake at a higher gestational age (p=0.001), among those who perceived that taking it brings benefits (p=0.018) and in those who perceived that consuming it had a high cost (p<0.001), on the contrary, those who had technical education (p=0.027), those who worked (p=0.002) and those who had some disability (p<0.001) took less calcium; adjusted for receiving an explanation of the benefits of taking this supplement Discussion: The vast majority of the respondents reported consuming calcium. Likewise, there were many factors that influenced positively and negatively for its greater consumption; therefore techniques should be used to encourage its use in pregnant women, which consist in explaining the benefits of this supplement.