RESUMO
In this study, we investigated the effectiveness of regional citrate anticoagulation continuous renal replacement therapy (RCA-CRRT) in reducing blood calcium levels in three patients with hypercalcemia crisis caused by different etiologies. The sodium citrate chelation of calcium ions was utilized as an anticoagulant for treating severely affected patients. By adjusting the citrate anticoagulant dose and monitoring treatment indicators, RCA-CRRT parameters were actively modified to alleviate the hypercalcemia crisis and provide time for surgery or specialized treatment. Two patients experienced rapid and effective reductions in blood calcium levels, allowing for further treatment, while the third patient exhibited a repeated increase in blood calcium, which eventually decreased after parathyroid adenoma resection, leading to clinical discharge. Our findings suggest that RCA-CRRT can help alleviate hypercalcemia crisis, stabilize the patient's internal environment, and provide valuable time for clinical treatment in cases of various medical conditions causing abnormal blood calcium elevations.
Assuntos
Anticoagulantes , Terapia de Substituição Renal Contínua , Hipercalcemia , Humanos , Hipercalcemia/sangue , Hipercalcemia/etiologia , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Terapia de Substituição Renal Contínua/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Cálcio/sangue , Resultado do Tratamento , Ácido Cítrico , Citrato de SódioRESUMO
In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.
Assuntos
Células Intersticiais do Testículo , Nanopartículas Magnéticas de Óxido de Ferro , Espermatogênese , Espermatozoides , Testículo , Testosterona , Animais , Masculino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro/toxicidade , Testículo/efeitos dos fármacos , Testículo/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Camundongos , Citrato de Sódio/toxicidadeRESUMO
BACKGROUND: Pseudothrombocytopenia (PTCP) is a relatively rare phenomenon in vitro, the mechanism is not completely clear, and there is no unified solution for it. How to identify and solve PTCP accurately is a challenge for laboratory personnel. METHODS: According to the patient's clinical manifestations, thrombocytopenia caused by hypersplenism was excluded. PTCP was confirmed by platelet volume histograms, scattergrams and platelet clumps on the blood smears. Commonly used alternative anticoagulants such as sodium citrate or heparin were used for platelet counting. The corrective effect of the platelet count was not good, so non-anticoagulant blood was collected and tested immediately, and blood smears were used to count platelets manually. RESULTS: The PTCP of the patient could not be solved using sodium citrate and heparin anticoagulation. By collecting non-anticoagulant blood and testing immediately, the platelet count returned to normal (180 x 109/L), which is consistent with the results of manual counting on the patient's blood smears (175 x 109/L). CONCLUSIONS: When PTCP is confirmed, commonly used alternative anticoagulants can be used. If these do not work, non-anticoagulant blood can be collected and tested immediately, and blood smears can be used to count platelets manually.
Assuntos
Carcinoma , Hiperesplenismo , Trombocitopenia , Humanos , Citrato de Sódio/farmacologia , Ácido Edético/farmacologia , Hiperesplenismo/diagnóstico , Agregação Plaquetária , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Anticoagulantes/uso terapêutico , Anticoagulantes/farmacologia , Heparina/uso terapêutico , Heparina/farmacologia , FígadoRESUMO
Gold nanoparticles (GNPs) are usually formed via a wet chemical method using gold (III) chloride trihydrate (GC), which is treated with stable reducing agents such as sodium citrate (SC). This study determines the effect of coloured light on the formation of GNPs by irradiation of SC after the addition of GC (SCGC) and the effect of the SCGC photolytic procedure on the suppression of WiDr colon cancer cells by forming reactive oxygen species. The absorbance of surface plasmon resonance peaks at 523 nm are 0.069 and 0.219 for SCGC when treated with blue light illumination (BLI) and violet light irradiation (VLI), respectively, whereas green and red light treatments have little or no effect. Most GNPs have diameters ranging from 3 to 15 nm, with a mean of 6 nm, when SCGC is exposed to VLI for 1.5 h. Anionic superoxide radicals (O2â¢-) are formed in a charge-transfer process after SCGC under VLI treatment; however, BLI treatment produces no significant reaction. Moreover, SCGC under VLI treatment proves to be considerably more effective at inhibiting WiDr cells than BLI treatment, as firstly reported in this study. The reduction rates for WiDr cells treated with SCGC under BLI and VLI at an intensity of 2.0 mW/cm2 for 1.5 h (energy dose, 10.8 J/cm2) are 4.1% and 57.7%, respectively. The suppression rates for WiDr cells treated with SCGC are inhibited in an irradiance-dependent manner, the inhibition percentages being 57.7%, 63.3%, and 80.2% achieved at VLI intensities of 2.0, 4.0, and 6.0 mW/cm2 for 1.5 h, respectively. Propidium iodide is a fluorescent dye that detects DNA changes after cell death. The number of propidium iodide-positive nuclei significantly increases in WiDr cells treated with SCGC under VLI, suggesting that SCGC photolysis under VLI is a potential treatment option for the photodynamic therapy process.
Assuntos
Neoplasias do Colo , Compostos de Ouro , Nanopartículas Metálicas , Humanos , Citrato de Sódio , Nanopartículas Metálicas/toxicidade , Ouro/farmacologia , Fotólise , Propídio , Neoplasias do Colo/tratamento farmacológicoRESUMO
BACKGROUND: Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is a rare phenomenon characterized by pseudo low platelet counts when using EDTA as anticoagulant and can result in false decision making of platelet transfusion. METHODS: An application for platelet transfusion from a patient who planned to undergo spinal surgery was received by the Department of Transfusion service. The preoperative laboratory test results showed thrombocytopenia (platelet counts: 27 x 109/L). The surgeon planned to transfuse platelets before the operation to avoid bleeding in operation due to thrombocytopenia. However, the lab technologist found that there was aggregation of platelets under the microscope. Samples used with sodium citrate and heparin as anticoagulants were rechecked. RESULTS: The platelet count of the patient was normal in sodium citrate and heparin anticoagulant tubes. The patient had no history and clinical symptoms of thrombocytopenia. Therefore, the doctor canceled the platelet order. We also reviewed the relevant literature of EDTA-PTCP. CONCLUSIONS: EDTA-PTCP is rare and may result of a wrong decision of platelet transfusion. Correct understanding and treatment of this situation can avoid unnecessary platelet transfusion.
Assuntos
Ácido Edético , Transfusão de Plaquetas , Trombocitopenia , Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Tomada de Decisão Clínica , Ácido Edético/efeitos adversos , Heparina/uso terapêutico , Citrato de Sódio/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/terapiaRESUMO
Nanomaterials are increasingly being employed for biomedical applications, necessitating a comprehensive understanding of their degradation behavior and potential toxicity in the biological environment. This study utilizes a continuous flow system to simulate the biologically relevant degradation conditions and investigate the effects of pH, protein, redox species, and chelation ligand on the degradation of iron oxide nanoparticles. The morphology, aggregation state, and relaxivity of iron oxide nanoparticles after degradation are systematically characterized. The results reveal that the iron oxide nanoparticles degrade at a significantly higher rate under the acidic environment. Moreover, incubation with bovine serum albumin enhances the stability and decreases the dissolution rate of iron oxide nanoparticles. In contrast, glutathione accelerates the degradation of iron oxide nanoparticles, while the presence of sodium citrate leads to the fastest degradation. This study reveals that iron oxide nanoparticles undergo degradation through various mechanisms in different biological microenvironments. Furthermore, the dissolution and aggregation of iron oxide nanoparticles during degradation significantly impact their relaxivity, which has implications for their efficacy as magnetic resonance imaging contrast agents in vivo. The results provide valuable insights for assessing biosafety and bridge the gap between fundamental research and clinical applications of iron oxide nanoparticles.
Assuntos
Meios de Contraste , Compostos Férricos , Compostos Férricos/química , Meios de Contraste/química , Citrato de Sódio , Nanopartículas Magnéticas de Óxido de FerroRESUMO
Metabolic reprogramming, as one of the characteristics of cancer, is associated with tumorigenesis, growth, or migration, and the modulation of metabolic pathways has emerged as a novel approach for cancer therapy. However, the conventional metabolism-mediated apoptosis process in tumor cells exhibits limited immunogenicity and inadequate activation of antitumor immunity. Herein, phospholipid-coated sodium citrate nanoparticles (PSCT NPs) are successfully prepared, which dissolve in tumor cells and then release significant amounts of citrate ions and Na+ ions. Massive quantities of ions lead to increased intracellular osmotic pressure, which activates the caspase-1/gasdermin D (GSDMD) mediated pyroptosis pathway. Simultaneously, citrate induces activation of the caspase-8/gasdermin C (GSDMC) pathway. The combined action of these two pathways synergistically causes intense pyroptosis, exhibiting remarkable antitumor immune responses and tumor growth inhibition. This discovery provides new insight into the potential of nanomaterials in modulating metabolism and altering cell death patterns to enhance antitumor immunotherapy.
Assuntos
Nanopartículas , Neoplasias , Humanos , Piroptose , Citrato de Sódio , Gasderminas , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias/tratamento farmacológico , Imunoterapia , Nanopartículas/uso terapêutico , Íons , Biomarcadores Tumorais , Proteínas Citotóxicas Formadoras de PorosRESUMO
Currently, the production of xylo-oligosaccharides (XOS) from lignocelluloses by chelating system hydrolysis has not been investigated. Herein, iron (III) chloride/sodium citrate (IC/SC) chelating system hydrolysis and xylanase hydrolysis were used to produce XOS from poplar. Then, the delignification of IC/SC-hydrolyzed poplar was performed by p-toluenesulfonic acid (p-TsOH) pretreatment to increase the accessibility of cellulase. The results demonstrated that 42.3% of XOS with an extremely low by-product (xylose/XOS = 0.11) was produced from poplar by 50 mM IC/SC hydrolysis (molar ratio of 1:1, 170 °C, 60 min) and xylanase hydrolysis. The second step IC/SC hydrolysis and xylanase hydrolysis of poplar increased the yield of XOS to 51.3%. Finally, the glucose yield of p-TsOH-pretreated poplar (60% p-TsOH, 70 °C, 30 min) was greatly increased from 37.5% to 83.8% by cellulase hydrolysis with Tween 80 addition. The novel strategy proposed in this work was feasible for XOS and monosaccharides production from poplar.
Assuntos
Celulases , Monossacarídeos , Cloretos , Citrato de Sódio , Ácido Cítrico , Hidrólise , Oligossacarídeos , Cloreto de Sódio , CitratosRESUMO
Pre-analytical factors have a significant influence on circulating microRNA (miRNA) profiling. The aim of this study was a comprehensive assessment of the impact of the anticoagulant type in blood collection tubes on circulating plasma miRNA profiles using small RNA sequencing. Blood from ten healthy participants (five males and five females from 25 to 40 years old) was taken in collection tubes with four different anticoagulants: acid citrate dextrose (ACD-B), sodium citrate, citrate-theophylline-adenosine-dipyridamole (CTAD) and dipotassium-ethylenediaminetetraacetic acid (K2 EDTA). Platelet-free plasma samples were obtained by double centrifugation. EDTA plasma samples had elevated levels of hemolysis compared to samples obtained using other anticoagulants. Small RNA was extracted from plasma samples and small RNA sequencing was performed on the Illumina NextSeq 500 system. A total of 30 samples had been successfully sequenced starting from ~1 M reads mapped to miRNAs, allowing us to analyze their diversity and isoform content. The principal component analysis showed that the EDTA samples have distinct circulating plasma miRNA profiles compared to samples obtained using other anticoagulants. We selected 50 miRNA species that were differentially expressed between the sample groups based on the type of anticoagulant. We found that the EDTA samples had elevated levels of miRNAs which are abundant in red blood cells (RBC) and associated with hemolysis, while the levels of some platelet-specific miRNAs in these samples were lowered. The ratio between RBC-derived and platelet-derived miRNAs differed between the EDTA samples and other sample groups, which was validated by quantitative PCR. This study provides full plasma miRNA profiles of 10 healthy adults, compares them with previous studies and shows that the profile of circulating miRNAs in the EDTA plasma samples is altered primarily due to an increased level of hemolysis.
Assuntos
MicroRNA Circulante , MicroRNAs , Adenosina , Adulto , Anticoagulantes/farmacologia , Coleta de Amostras Sanguíneas , Citratos , Dipiridamol , Ácido Edético/farmacologia , Feminino , Hemólise , Humanos , Masculino , MicroRNAs/genética , Análise de Sequência de RNA , Citrato de Sódio , TeofilinaRESUMO
Achromobacter spp. are increasingly recognized as emerging pathogens in immunocompromised patients or suffering cystic fibrosis, but unusual in immunocompetent hosts or individuals that underwent surgery. In this study we describe two simultaneous events attributable to two different Achromobacter spp. contaminated sources. One event was related to an episode of pseudo-bacteremia due to sodium citrate blood collection tubes contaminated with Achromobacter insuavis and the other to Achromobacter genogroup 20 infection and colonization caused by an intrinsically contaminated chlorhexidine soap solution. Both threatened the appropriate use of antimicrobials. Molecular approaches were critical to achieving the accurate species identification and to assess the clonal relationship, strengthening the need for dedicated, multidisciplinary and collaborative work of microbiologists, specialists in infectious diseases, epidemiologists and nurses in the control of infections to clarify these epidemiological situations.
Assuntos
Achromobacter , Infecção Hospitalar , Infecções por Bactérias Gram-Negativas , Achromobacter/genética , Clorexidina , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Sabões , Citrato de SódioRESUMO
Buffering agents have not been comprehensively profiled in terms of their capacity to influence water retention prior to exercise. The purpose of this investigation was to profile the fluid retention characteristics of sodium bicarbonate (BIC) and sodium citrate (CIT) to determine the efficacy of these buffering mediums as hyperhydrating agents. Nineteen volunteers (13 males and six females; age = 28.3 ± 4.9 years) completed three trials (randomized and cross-over design). For each trial, a baseline measurement of body mass, capillary blood, and urine was collected prior to ingestion of their respective condition (control condition [CON] = 25 ml/kg artificially sweetened water; BIC condition = CON + 7.5 g/L of sodium in the form of BIC; CIT condition = CON + 7.5 g/L of sodium in the form of CIT). The fluid loads were consumed in four equal aliquots (0, 20, 40 and 60 min; fluid intake was 1.972 ± 361 ml [CON]; 1.977 ± 360 ml [BIC]; 1.953 ± 352 ml [CIT]). Samples were recorded at 20 (body mass and urine) and 60 min (blood) intervals for 180 min. Blood buffering capacity (HCO3-) was elevated (p < .001) in both BIC (32.1 ± 2.2 mmol/L) and CIT (28.9 ± 3.8 mmol/L) at 180 min compared with CON (25.1 ± 1.8 mmol/L). Plasma volume expansion was greater (p < .001) in both BIC (8.1 ± 1.3%) and CIT (5.9 ± 1.8%) compared with CON (-1.1 ± 1.4%); whereas, total urine production was lower in BIC and CIT at 180 min (BIC vs. CON, mean difference of 370 ± 85 ml; p < .001; CIT vs. CON, mean difference of 239 ± 102 ml; p = .05). There were no increases observed in body mass (p = .9). Under resting conditions, these data suggest BIC and CIT induce a greater plasma hypervolemic response as compared with water alone.
Assuntos
Bicarbonato de Sódio , Edulcorantes , Adulto , Bicarbonatos , Feminino , Humanos , Masculino , Sódio , Bicarbonato de Sódio/farmacologia , Citrato de Sódio , Água , Adulto JovemRESUMO
Sodium citrate (SC) is a widely-used food and industrial additive with the properties of complexation and microbial degradation. In the present study, nano-zero-valent iron reaction system (SC-nZVI@BC) was successfully established by modifying nanoscale zero-valent iron (nZVI) with SC and biochar (BC), and was employed to remove Cr(â ¥) from aqueous solutions. The nZVI, SC-nZVI and SC-nZVI@BC were characterized and compared using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analyses (TGA), vibrating sample magnetometer (VSM), scanning electron microscope (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results showed that nZVI was successfully loaded on the biochar, and both the agglomeration and surface passivation problems of nanoparticles were well resolved. The dosage of SC, C:Fe, initial pH and Cr(â ¥) concentration demonstrated direct effects on the removal efficiency. The maximum Cr(â ¥) removal rate and the removal capacity within 60 min were 99.7% and 199.46 mg/g, respectively (C:Fe was 1:1, SC dosage was 1.12 mol.%, temperature was 25°C, pH = 7, and the original concentration of Cr(â ¥) was 20 mg/L). The reaction confirmed to follow the pseudo-second-order reaction kinetics, and the order of the reaction rate constant k was as follows: SC-nZVI@BC > nZVI@BC > SC-nZVI > nZVI. In addition, the mechanism of Cr(â ¥) removal by SC-nZVI@BC mainly involved adsorption, reduction and co-precipitation, and the reduction of Cr(â ¥) to Cr(â ¢) by nano Fe0 played a vital role. Findings from the present study demonstrated that the SC-nZVI@BC exhibited excellent removal efficiency toward Cr(â ¥) with an improved synergistic characteristic by SC and BC.
Assuntos
Ferro , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Cromo , Citrato de Sódio , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: New strategies are needed to combat multidrug-resistant bacteria. The restriction of iron uptake by bacteria is a promising way to inhibit their growth. We aimed to suppress the growth of Vibrio bacterial species by inhibiting their ferric ion-binding protein (FbpA) using food components. METHODS: Twenty spices were selected for the screening of FbpA inhibitors. The candidate was applied to antibacterial tests, and the mechanism was further studied. RESULTS: An active compound, rosmarinic acid (RA), was screened out. RA binds competitively and more tightly than Fe3+ to VmFbpA, the FbpA from V. metschnikovii, with apparent KD values of 8 µM vs. 17 µM. Moreover, RA can inhibit the growth of V. metschnikovii to one-third of the control at 1000 µM. Interestingly, sodium citrate (SC) enhances the growth inhibition effect of RA, although SC only does not inhibit the growth. The combination of RA/SC completely inhibits the growth of not only V. metschnikovii at 100/100 µM but also the vibriosis-causative pathogens V. vulnificus and V. parahaemolyticus, at 100/100 and 1000/100 µM, respectively. However, RA/SC does not affect the growth of Escherichia coli. CONCLUSIONS: RA/SC is a potential bacteriostatic agent against Vibrio species while causing little damage to indigenous gastrointestinal bacteria.
Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Ferro/metabolismo , Citrato de Sódio/farmacologia , Vibrio parahaemolyticus/efeitos dos fármacos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Cinamatos/química , Cinamatos/metabolismo , Depsídeos/química , Depsídeos/metabolismo , Sinergismo Farmacológico , Proteínas de Ligação ao Ferro/química , Proteínas de Ligação ao Ferro/metabolismo , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Ligação Proteica , Vibrio parahaemolyticus/metabolismo , Ácido RosmarínicoRESUMO
The conjugation of biomolecules to magnetic nanoparticles has emerged as promising approach in biomedicine as the treatment of several diseases, such as cancer. In this study, conjugation of bioactive peptide fractions from germinated soybeans to magnetite nanoparticles was achieved. Different fractions of germinated soybean peptides (>10 kDa and 5-10 kDa) were for the first time conjugated to previously coated magnetite nanoparticles (with 3-aminopropyltriethoxysilane (APTES) and sodium citrate) by the Ugi four-component reaction. The crystallinity of the nanoparticles was corroborated by X-ray diffraction, while the particle size was determined by scanning transmission electron microscopy. The analyses were carried out using infrared and ultraviolet-visible spectroscopy, dynamic light scattering, and thermogravimetry, which confirmed the coating and functionalization of the magnetite nanoparticles and conjugation of different peptide fractions on their surfaces. The antioxidant activity of the conjugates was determined by the reducing power and hydroxyl radical scavenging activity. The nanoparticles synthesized represent promising materials, as they have found applications in bionanotechnology for enhanced treatment of diseases, such as cancer, due to a higher antioxidant capacity than that of fractions without conjugation. The highest antioxidant capacity was observed for a >10 kDa peptide fraction conjugated to the magnetite nanoparticles coated with APTES.
Assuntos
Antioxidantes/farmacologia , Glycine max/química , Nanopartículas de Magnetita/química , Peptídeos/farmacologia , Antioxidantes/química , Sequestradores de Radicais Livres/química , Germinação , Tamanho da Partícula , Peptídeos/química , Propilaminas/química , Silanos/química , Citrato de Sódio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios XRESUMO
Nanomedicine is seen as a potential central player in the delivery of personalized medicine. Biocompatibility issues of nanoparticles have largely been resolved over the past decade. Despite their tremendous progress, less than 1% of applied nanosystems can hit their intended target location, such as a solid tumor, and this remains an obstacle to their full ability and potential with a high translational value. Therefore, achieving immune-tolerable, blood-compatible, and biofriendly nanoparticles remains an unmet need. The translational success of nanoformulations from bench to bedside involves a thorough assessment of their design, compatibility beyond cytotoxicity such as immune toxicity, blood compatibility, and immune-mediated destruction/rejection/clearance profile. Here, we report a one-pot process-engineered synthesis of ultrasmall gold nanoparticles (uGNPs) suitable for better body and renal clearance delivery of their payloads. We have obtained uGNP sizes of as low as 3 nm and have engineered the synthesis to allow them to be accurately sized (almost nanometer by nanometer). The synthesized uGNPs are biocompatible and can easily be functionalized to carry drugs, peptides, antibodies, and other therapeutic molecules. We have performed in vitro cell viability assays, immunotoxicity assays, inflammatory cytokine analysis, a complement activation study, and blood coagulation studies with the uGNPs to confirm their safety. These can help to set up a long-term safety-benefit framework of experimentation to reveal whether any designed nanoparticles are immune-tolerable and can be used as payload carriers for next-generation vaccines, chemotherapeutic drugs, and theranostic agents with better body clearance ability and deep tissue penetration.
Assuntos
Materiais Biocompatíveis , Ouro , Imunidade Inata , Nanopartículas Metálicas , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Coagulação Sanguínea/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ouro/química , Ouro/toxicidade , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/fisiologia , Teste de Materiais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Modelos Imunológicos , Citrato de Sódio , Células THP-1 , TaninosRESUMO
Extracellular pH (pHe) of tumor cells is characteristic of tumor microenvironment (TME). Acidic TME impairs the responses of tumors to some anti-cancer chemotherapies. In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO3- concentrations, corresponding to increase of HCO3- concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3-, an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1®, an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of anticancer agents for pancreatic cancer in the end stage.
Assuntos
Antiácidos/administração & dosagem , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Ácido Oxônico/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Administração Oral , Animais , Antiácidos/farmacocinética , Linhagem Celular Tumoral , Combinação de Medicamentos , Sinergismo Farmacológico , Espaço Extracelular/química , Espaço Extracelular/efeitos dos fármacos , Feminino , Humanos , Camundongos , Ácido Oxônico/farmacocinética , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/patologia , Citrato de Potássio/administração & dosagem , Citrato de Potássio/farmacocinética , Citrato de Sódio/administração & dosagem , Citrato de Sódio/farmacocinética , Tegafur/farmacocinética , Tegafur/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Acute graft-versus-host disease (aGvHD) remains lethal as a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Inflammatory responses play an important role in aGvHD. 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) has been widely reported to have a major effect on the anti-inflammatory response; however, these effects in aGvHD models have never been reported. In this study, a murine aGvHD model was developed by transferring spleen cells from donor B6/N (H-2kb) mice into recipient B6D2F1 (H-2kb/d) mice. In addition to evaluating manifestations in aGvHD mice, we analyzed the serum ALT/AST levels, liver pathological changes, infiltrating cells and mRNA expression of inflammation-related cytokines and chemokines. 5-ALA/SFC treatment significantly ameliorated liver injury due to aGvHD and decreased the population of liver-infiltrating T cells, resulting in a reduced expression of pro-inflammatory cytokines and chemokines. Furthermore, the mRNA expression proliferator-activated receptor-γcoactivator (PGC-1α) was enhanced, which might explain why 5-ALA/SFC treatment downregulates inflammatory signaling pathways. Our results indicated that 5-ALA/SFC can ameliorate liver injury induced by aGvHD through the activation of PGC-1α and modulation of the liver mRNA expression of inflammatory-related cytokines and chemokines. This may be a novel strategy for treating this disease.
Assuntos
Citocinas/genética , Compostos Ferrosos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Ácidos Levulínicos/administração & dosagem , Fígado/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Regulação para Cima , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Ácido Cítrico , Modelos Animais de Doenças , Quimioterapia Combinada , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Ácidos Levulínicos/farmacologia , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Citrato de Sódio/química , Linfócitos T/metabolismo , Resultado do Tratamento , Ácido AminolevulínicoRESUMO
OBJECTIVES: We have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. We also aimed to determine whether sodium citrate is beneficial in treating qualitative olfactory dysfunction. METHODS: We performed a prospective, controlled study. Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The left nasal cavity was untreated and, therefore, acted as an internal control. Monorhinal olfactory function was assessed using the "Sniffin' Sticks" composite 'TDI' score, before and after treatment. The presence of parosmia and phantosmia was also assessed. RESULTS: Overall, there was a significant increase in TDI after treatment (using the best of right and left sides). Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. The proportion of patients reporting parosmia did not change significantly after treatment. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. CONCLUSIONS: Treatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. It may, however, be beneficial in treating phantosmia, which should be further addressed in future work.
Assuntos
Transtornos do Olfato , Administração Intranasal , Humanos , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/etiologia , Estudos Prospectivos , Olfato , Citrato de Sódio/uso terapêuticoRESUMO
The apigenin is a bioactive flavonoid mostly found in fruits and vegetables that possess various biological activities. The current study was performed to compare the biological potentials of sodium citrate-based (SC-SNPs) and apigenin-based (AP-SNPs) synthesized silver nanoparticles under the in vitro and in vivo conditions. The synthesized silver nanoparticles were physically and chemically characterized. The anticancer, pro-apoptotic, and their anti-bacterial activities were determined. Further, the mice trial was conducted to determine the possible toxic effects of the synthesized silver nanoparticles. The result of particle size analysis revealed the nanometer sizes of the SC-SNPs and AP-SNPs were about 95.5 and 93.94 nm, respectively. Both nanoparticles indicated pseudo-spherical shape, homogenous dispersion with an appropriate good degree of stability. However, the anticancer potential, pro-apoptotic effects and antibacterial activity of AP-SNPs were higher than that of SC-SNPs. Moreover, the mice trial indicated that AP-SNPs improved the liver function through modulation of liver enzymes, lipid peroxidation, and increase in the expression of antioxidant enzymes (SOD and GPx) as compared to the mice received AP-SNPs during 30 day experiment. Consequently the synthesis of silver nanoparticles using apigenin as reducing bioactive compound may result in production of silver nanoparticles with enhanced anticancer, antibacterial and antioxidant activities.