ABSTRACT
Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of vinyl pyrrolidone/vinyl acetate copolymer (Kollidon® VA64, VA64) and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm2 (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90% of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODF treatment group had a 100% reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7% higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group showed minimal oral irritation, scoring only 1 point and a 65% preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment product development.
Subject(s)
Borates , Eugenol , Oral Ulcer , Eugenol/administration & dosage , Eugenol/pharmacology , Animals , Rats , Borates/administration & dosage , Oral Ulcer/drug therapy , Male , Administration, Oral , Drug Delivery Systems/methods , Drug Liberation , Hypromellose Derivatives/chemistry , Rats, Wistar , Tensile StrengthABSTRACT
BACKGROUND: Obesity is one of the most popular topic in the field of research. In order to defeat this highly widespread disease, the mechanism of fat accumulation at the molecular level and its elimination are crucial. The use of boron has been showing promising results during the recent years. METHODS: In this study, anti-obesity potential of Sodium Pentaborate Pentahydrate (SPP) used as a dietary supplement on BALB/c mice fed with a high-fat diet was evaluated. Mice were divided into four groups with different diets, consisting of a normal diet, a high-fat diet (HFD) (containing 60 % fat), a HFD-supplemented with 0.5 mg/g body weight (BW) of SPP and a HFD-supplemented with 1.5 mg/g body weight (BW) of SPP. The animals were then observed for 10 weeks and physically monitored, and were sacrificed at the end of the experiment for physical and physicochemical evaluation. RESULTS: According to the physical parameters measured -body weight, food and water intake ratios-, the results indicate that SPP decreased weight gain in a dose dependent manner. Measurement of the hormone levels in the blood and fat accumulation in organs of mice also supported the anti-obesity effects of SPP. Expressions of adipogenesis related genes were also negatively regulated by SPP administration in white adipose tissue (WAT) tissue. CONCLUSION: These findings promise a treatment approach and drug development that can be used against obesity when SPP is used in the right doses. As a future aspect, clinical studies with SPP will reveal the effect of boron derivatives on obesity.
Subject(s)
Anti-Obesity Agents/pharmacology , Borates/pharmacology , Lipids/antagonists & inhibitors , Obesity/drug therapy , Administration, Oral , Animals , Anti-Obesity Agents/administration & dosage , Borates/administration & dosage , Diet, High-Fat/adverse effects , Dose-Response Relationship, Drug , Female , Mice , Mice, Inbred BALB C , Obesity/chemically inducedABSTRACT
INTRODUCTION: Calls to poison control about exposure to household cleaners have increased during the COVID-19 pandemic. This dynamic may reflect increased exposure from public health efforts as well as health misinformation shared on social media. METHODS: We analyzed the dynamics of calls to the Regional Center for Poison Control and Prevention serving Massachusetts and Rhode Island (MARI PCC) and tweets discussing treating COVID-19 with house cleaners from January 20, 2020 to May 5, 2020. We obtained publicly available tweets discussing the use of household cleaners to "cure COVID" from the same time period with geographic co-ordinates indicating that they were emitted from the Greater Boston Area. RESULTS: Our main finding is that public health efforts were followed by a sustained increase in calls after March 15, 2020 (10 ± 2 calls per day before to 15 ± 2.5 after) while misinformation on social media was associated with intermittent spikes in calls. Overall, calls significantly increased during the study period by 34% as compared to the previous 8 years, mostly reporting unintentional ingestions with no serious effects. The daily volume of tweets and retweets was significantly correlated with daily call rates to MARI PCC for the surrounding 7-10 days. CONCLUSIONS: Health misinformation on social media about using household cleaning agents to treat COVID-19 and public health efforts lead to different dynamics in PCC calls. Public health efforts were followed by a sustained increase in calls after March 15, 2020 while misinformation on social media was followed by intermittent spikes in calls. This analysis is the first to link the geospatial dynamics of social media and public health interventions to poison center calls about exposure to household cleaners.
Subject(s)
COVID-19/therapy , Communication , Detergents , Poison Control Centers , Social Media , Ammonia/administration & dosage , Ammonia/adverse effects , Ammonia/poisoning , Borates/administration & dosage , Borates/adverse effects , Borates/poisoning , Boston , COVID-19/psychology , Detergents/administration & dosage , Detergents/adverse effects , Detergents/poisoning , Humans , Massachusetts , Phenol/administration & dosage , Phenol/adverse effects , Phenol/poisoning , Poison Control Centers/statistics & numerical data , Poisson Distribution , Rhode Island , Social Media/statistics & numerical data , Social Media/trends , Sodium Hypochlorite/administration & dosage , Sodium Hypochlorite/adverse effects , Sodium Hypochlorite/poisoningABSTRACT
Boron is an essential trace element in cellular metabolism; however, the molecular mechanism of boron in the heart is unclear. In this study, we examined the effect of sodium tetraborate (as boron source) as a possible protective agent or competitive inhibitor of cardiac hypertrophy in an in vitro murine model. We evaluated different previously reported sodium tetraborate concentrations and it was found that 13⯵M improves viability without affecting the cellular structure. We demonstrated that cardiomyocytes pretreated with sodium tetraborate prevents cellular damage induced by isoproterenol (cardioprotective effect) by increasing proliferation rate and inhibiting apoptosis. In addition, the reduction of the expression of the α1AR and ß1AR adrenergic receptors as well as Erk1/2 was notable. Consequently, the expression of the early response genes c-myc, c-fos and c-jun was delayed. Also, the expression of GATA-4, NFAT, NKx2.5 and myogenin transcription factors involved in sarcomere synthesis declined. In contrast, cardiomyocytes, when treated simultaneously with sodium tetraborate and isoproterenol, did not increase their size (cytoplasmic gain), but an increase in apoptosis levels was observed; therefore, the proliferation rate was reduced. Although the mRNA levels of α1AR and ß1AR as well as Erk1/2 and Akt1 were low at 24â¯h, their expression increased to 48â¯h. Notably, the mRNA of expression levels of c-myc, c-fos and c-jun were lower than those determined in the control, while the transcription factors GATA-4, MEF2c, Nkx2.5, NFAT and CDk9 were determined in most cells. These results suggest that pretreatment with sodium tetraborate in cardiomyocytes inhibits the hypertrophic effect. However, sodium tetraborate attenuates isoproterenol induced hypertrophy damage in cardiomyocytes when these two compounds are added simultaneously.
Subject(s)
Borates/pharmacology , Cardiomegaly/chemically induced , Cardiomegaly/metabolism , Cardiotonic Agents/pharmacology , Myocytes, Cardiac/drug effects , Animals , Apoptosis/drug effects , Borates/administration & dosage , Borates/adverse effects , Cardiotonic Agents/adverse effects , Cell Proliferation/drug effects , Cells, Cultured , Gene Expression Regulation/drug effects , Isoproterenol/administration & dosage , Isoproterenol/adverse effects , MAP Kinase Signaling System/drug effects , Mice, Inbred BALB C , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Adrenergic, alpha-1/genetics , Receptors, Adrenergic, beta-2/genetics , Signal Transduction/drug effects , Transcription Factors/metabolismABSTRACT
Purpose: Natamycin (NTM) ophthalmic suspension is the only FDA-approved formulation commercially available for treating ocular fungal infections. However, precorneal residence times and losses/drainage remain the foremost challenges associated with current ocular antifungal pharmacotherapy. In our previous investigations, NTM loaded polyethylene glycol nanolipid carriers (NTM-PNLCs) showed enhanced corneal permeation, both in vitro and in vivo. To further improve the corneal retention of NTM-PNLCs, this study aimed to develop a gelling system composed of carboxyvinyl polymer, guar gum, and boric acid in which the NTM-PNLCs were loaded. Methods: A 23 factorial design was employed in formulating and optimizing the gelling system for NTM-PNLCs, where the independent factors were the gelling excipients (guar gum, boric acid, and Carbopol® 940) and dependent variables were gelling time, gel depot collapse time, rheology, firmness, and work of adhesion. Optimized gel was evaluated for transcorneal permeation using rabbit cornea, in vitro; and tear pharmacokinetics and ocular biodistribution in male New Zealand White rabbits, in vivo. Results: Optimized NTM-PNLC-GEL was found to exhibit shear thinning rheology, adequate firmness, and spreadability, and formed a depot that did not collapse immediately. In addition, the in vitro transcorneal evaluation studies indicated that the NTM-PNLC-GEL exhibited a lower/slower flux and rate in comparison to Natacyn® suspension. NTM-PNLC-GEL (0.3%), at a 16-fold lower dose, exhibited mean residence time and elimination half-life comparable to Natacyn (5%), and provided similar in vivo concentrations in the innermost tissues of the eye. Conclusion: The data indicate that the NTM-PNLC-GEL formulation could serve as an alternative during ophthalmic antifungal therapy.
Subject(s)
Antifungal Agents/pharmacokinetics , Drug Compounding/methods , Eye Infections, Fungal/drug therapy , Gels/administration & dosage , Nanoparticles/administration & dosage , Natamycin/pharmacokinetics , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Borates/administration & dosage , Borates/chemistry , Cornea/physiology , Cyamopsis/chemistry , Drug Carriers/chemistry , Drug Carriers/metabolism , Gels/chemistry , Male , Nanoparticles/chemistry , Natamycin/administration & dosage , Natamycin/adverse effects , Natamycin/therapeutic use , Ophthalmic Solutions/administration & dosage , Permeability/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Polymers/administration & dosage , Polymers/chemistry , Rabbits , Tissue Distribution/drug effectsABSTRACT
Among emerging biomaterials, bioactive glasses (BGs) are being widely explored for various applications in tissue engineering. However, the effects of BGs (in particular BG ionic dissolution products) on immune cells and specifically on dendritic cells (DCs), which are the most potent antigen-presenting cells of the immune system, have not been previously investigated in detail. Such interactions between BGs and DCs must be assessed as a novel biocompatibility criterion for biomaterials, since, with the increased application possibilities of BGs, the modulation of the immune system may induce potential complications and undesired side effects. Indeed, the effects of BG exposure on specific immune cells are not well understood. Thus, in this study we investigated, for the first time, the effect of borate BGs doped with biologically active ions on specific immune cells, such as DCs and we further investigated the antibacterial properties of these borate BGs. The compositions of the borate BGs (B3) were based on the well-known 13-93 (silicate) composition by replacing silica with boron trioxide and by adding copper (3 wt%) and/or zinc (1 wt%). By performing an agar diffusion test, the antibacterial effect depending on the compositions of the borate BGs could be proved. Furthermore we found a dose-dependent immune modulation of DCs after treatment with borate BGs, especially when the borate BGs contained Zn and/or Cu. Depending on the ion concentration and the rise in pH, the phenotype and function of DCs were modified. While at low doses B3 and Zn-doped B3 BGs had no impact on DC viability, Cu containing BGs strongly affected cell viability. Furthermore, the surface expression of DC-specific activation markers, such as the major histocompatibility complex (MHC)-II, CD86 and CD80, was modulated. In addition, also DC mediated T-cell proliferation was remarkably reduced when treated with high doses of B3-Cu and B3-Cu-Zn BGs. Interestingly, the release of inflammatory cytokines increased after incubation with B3 and B3-Zn BGs compared to mock-treated DCs. Considering the essential role of DCs in the modulation and regulation of immune responses, these findings provide first evidence of phenotypic and functional consequences regarding the exposure of DCs to BGs in vitro.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Borates/administration & dosage , Copper/administration & dosage , Dendritic Cells/drug effects , Glass , Zinc/administration & dosage , Animals , Anti-Bacterial Agents/chemistry , Borates/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Copper/chemistry , Cytokines/metabolism , Dendritic Cells/metabolism , Glass/chemistry , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Zinc/chemistryABSTRACT
One of the most commonly used near infrared (NIR) dyes is indocyanine green (ICG), which has been extensively used for NIR bioimaging, photothermal and photodynamic therapy. However, upon excitation this dye can react with molecular oxygen to form singlet oxygen (SO), which can then cleave ICG to form non-fluorescent debris. In order to reduce the reaction between ICG and oxygen, we used energy transfer (ET) between the former and the NIR dye IR-1061. The two dyes were encapsulated in micelles composed of biocompatible poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG). Micelles were characterized for their size using dynamic light scattering (DLS) and were found to measure about 35 nm in diameter. Fluorescence emission measurements were conducted to show that the stability of ICG against photodecomposition is increased. Moreover, this increased stability allows the encapsulated dye to generate more heat and for a longer time, compared to its free form. Studies with a SO indicator showed that as more IR-1061 is added to the micelles, less SO is produced. These results show how by changing the amount of added IR-1061 it is possible to tune the heat and SO generated by the system. Cell viability studies demonstrated that while particles were nontoxic under physiological conditions, upon 808 nm irradiation they become potent at eradicating MCF7 cancer cells. Moreover, it was demonstrated that both the increase of temperature and the creation of decomposition debris play a role in the cytotoxic efficacy of the micelles. Dye-loaded micelles that were injected to live mice showed bright fluorescence in the over 1000 nm NIR (OTN-NIR) region, allowing for visualization of blood vessels and internal organs. Most importantly, the encapsulated dyes remained stable for over 30 minutes, gradually accumulating in the liver and spleen. The presence of IR-1061 in addition to the heat-generating dye ICG allowed for simultaneous temperature modification and monitoring. We were able to assess the change in temperature by measuring the change in the fluorescence intensity of IR-1061 in the OTN-NIR region, a range with deep penetration of living tissues. These features illustrate the potential use of ICG/IR-1061 in PCL-PEG micelles as promising candidates for cancer treatment and diagnosis.
Subject(s)
Borates/administration & dosage , Coloring Agents/administration & dosage , Indocyanine Green/administration & dosage , Lactones/administration & dosage , Micelles , Neoplasms/drug therapy , Polyethylene Glycols/administration & dosage , Pyrans/administration & dosage , Animals , Borates/chemistry , Coloring Agents/chemistry , Female , Humans , Indocyanine Green/chemistry , Lactones/chemistry , Light , MCF-7 Cells , Mice, Inbred ICR , Optical Imaging , Photochemotherapy , Polyethylene Glycols/chemistry , Pyrans/chemistryABSTRACT
Tumor microenvironment, genetic, and non-genetic factors are responsible for the atypical metabolic feature of cancer cells. Aberrant activity of PI3K/Akt pathway, increased glycolytic flux, and decreased intracellular pH gradient are the leading causes of this feature. Calcium Fructoborate (CaFB), a sugar-borate ester, has major benefits for human health. The aim of this study was to explore the implication of CaFB on experimentally induced skin cancer in vivo. According to the treatment, 92 female Balb-c mice are divided into six groups: control, CaFB (3 mg/kg/day), 7,12-Dimethylbenz(a)anthracene (DMBA)+12-O-tetradecanoylphorbol-13-acetate (TPA) (97.5 nmol DMBA, 6.5 nmol TPA), T1: CaFB+DMBA+TPA (3 mg/kg/day CaFB together with DMBA), T2: DMBA+CaFB+TPA (3 mg/kg/day CaFB together with TPA), T3: DMBA+TPA+CaFB (3 mg/kg/day CaFB after tumor formation). Topical DMBA and TPA application resulted in a significant increase in the protein levels, immunoreactivity, and mRNA expression of HRAS, HIF1α, Akt, and PTEN (p < 0.05). Moreover, an increase in the number of TUNEL-positive cells was observed in DMBA-TPA group compared with the control group (p < 0.05). CaFB application reduced the protein levels, immunoreactivity, and mRNA expressions of HRAS, HIF1α, Akt, and PTEN and also decreased the number of TUNEL-positive cells. Recent evidence obtained from our study validated that CaFB treatment may have skin cancer-preventing effect.
Subject(s)
Borates/pharmacology , Fructose/analogs & derivatives , Skin Neoplasms/prevention & control , Administration, Oral , Animals , Borates/administration & dosage , Female , Fructose/administration & dosage , Fructose/pharmacology , Mice , Mice, Inbred BALB C , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
Heavy metals have harmful effects on health of both ecosystems and organisms to their accumulation ability. Copper (Cu) is an essential element for organism survival, but EPA considers Cu as a priority pollutant. On the other hand, boron has well-defined biological effects in living organisms including cytoprotection and genoprotection, although borax (BX) metabolism is poorly described in fish. Moreover, the effects of boron supplementation against Cu-induced hematotoxicity and DNA damage in aquatic organisms are still undetermined. Therefore, the main aim of this study was to provide an overview of the strategy for therapeutic potential of BX against Cu exposure in rainbow trout, Oncorhynchus mykiss. For this aim, fish were fed with different doses of BX and/or copper (1.25, 2.5, and 5 mg/kg of BX; 500 and 1000 mg/kg of Cu) for 21 days in pretreatment and combined treatment options. At the end of the treatments (pre and combined), the hematological index (total erythrocytes count (RBC), total leucocytes count (WBC), hemoglobin (Hb), hematocrit (Hct), total platelet count (PLT), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean cell volume (MCV)), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), and nuclear abnormalities in blood samples of treated and untreated fish were investigated. The statistically significant (p < 0.05) and dose-dependent increases in hematological indices, 8-OH-dG level, and rates of nuclear abnormalities were observed after exposure to Cu in both treatment group fish as compared to untreated group. On the contrary, treatments with BX doses alone did not alter these hematological and DNA damage endpoints. Moreover, both pretreatment and combined treatments with BX significantly alleviated Cu-induced hematotoxicity and genotoxicity. In a conclusion, the obtained data firstly revealed that borax exhibited hematoprotective and genoprotective effects against copper-induced toxicity in fish.
Subject(s)
Borates/pharmacology , Copper/toxicity , DNA Damage , Oncorhynchus mykiss/genetics , Animals , Borates/administration & dosage , Borates/metabolism , Copper/administration & dosage , Dietary Supplements , Dose-Response Relationship, Drug , Erythrocyte Count , Hemoglobins/metabolism , Leukocyte CountABSTRACT
We aimed to investigate the modulating effects of dietary borax on the pathways in rainbow trout brain exposed to copper. For this aim, a comprehensive assessment was performed including biochemical (acetylcholinesterase (AChE), malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3 levels) and transcriptional parameters (heat shock protein 70 (HSP70) and cytochromes P450 (CYP1A), glutathione peroxidase (gpx), superoxide dismutase (sod), and catalase (cat)) parameters and immunohistochemically staining of 8-OHdG. Special fish feed diets were prepared for the trial. These diets contained different concentrations of borax (1.25, 2.5, and 5 mg/kg) and/or copper (500 and 1000 mg/kg) at the period of pre- and co-treatment strategies for 21 days. At the end of the treatment periods, brain tissue was sampled for each experimental group. As a result, the biochemical parameters were increased and AChE activity decreased in the copper and copper-combined groups in comparison with the control group and also with only borax applications (p < 0.05). We observed an increase or decrease in particular biochemical parameters for the borax group in every application and we established that borax had protective effect against copper toxicity by decreasing and/or increasing the relevant biochemical parameters in brain tissue of fish. The biochemical results of borax and its combinations corresponded to the observations of gene expression data, which similarly concluded that HSP70 and CYP1A genes were strongly induced by copper (p < 0.05). In addition, the expression levels of the sod, cat, and gpx genes in the fish brains exposed to borax and the borax combination groups were significantly higher than the only copper-treated groups. In conclusion, borax supplementation provided significant protection against copper-induced neurotoxicity in trout.
Subject(s)
Borates/pharmacology , Copper/toxicity , Fish Diseases/chemically induced , Neuroprotective Agents/pharmacology , Oncorhynchus mykiss , 8-Hydroxy-2'-Deoxyguanosine , Animals , Borates/administration & dosage , Caspase 3/genetics , Caspase 3/metabolism , Copper/administration & dosage , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Dose-Response Relationship, Drug , Fish Diseases/blood , Fish Diseases/metabolism , Gene Expression Regulation/drug effects , Neuroprotective Agents/administration & dosageABSTRACT
STATEMENT OF PROBLEM: Controlled clinical trials comparing the effectiveness of the walking bleaching (WB) technique and the inside-outside (I-O) technique used in a short daily regimen are lacking. PURPOSE: The purpose of this randomized clinical trial was to investigate the effectiveness of WB with that of the I-O technique conducted over 4 weeks and to compare color changes after 1 year. MATERIAL AND METHODS: Discolored and endodontically treated anterior teeth received a cervical seal and were randomly divided into groups according to the technique. In the WB group (n=9), a mixture of sodium perborate and 20% hydrogen peroxide was applied in the pulp chambers and replaced weekly up to 4 weeks. For the I-O group (n=8), participants applied 10% carbamide peroxide in the pulp chambers and wore custom-fitted trays for 1 hour per day over 4 weeks. CIELab parameters were obtained using a spectrophotometer at baseline, during bleaching (1, 2, 3, and 4 weeks) and after 1 year. Changes in color (ΔE), lightness (ΔL*), green-red axis (Δa*), blue-yellow axis (Δb*), and absolute color parameters (L*, b*, and a*) for each evaluation time were calculated and analyzed by repeated measures analysis of variance (ANOVA) and post hoc Bonferroni test (α=.05). RESULTS: No significant differences between WB and I-O techniques were observed for ΔE, ΔL*, Δa*, Δb*, L*, a*, or b* values (P>.05); however, significant differences were observed among the evaluation times (P<.05). Color changes observed after 2 weeks were stable after 1 year; ΔL* and Δa* values after 1 year were not significantly different from the 1-week evaluation, and significant changes in Δb* after 3 weeks were maintained at the 1-year follow-up. The same trend was observed for the absolute CIELab color parameters. CONCLUSIONS: Both WB and I-O regimens were similarly effective as shown by significant ΔE after 2 weeks and no color regression after 1 year.
Subject(s)
Tooth Bleaching/methods , Tooth, Nonvital , Adult , Borates/administration & dosage , Carbamide Peroxide , Female , Follow-Up Studies , Humans , Hydrogen Peroxide/administration & dosage , Male , Oxidants/administration & dosage , Peroxides/administration & dosage , Time Factors , Tooth Bleaching Agents/administration & dosage , Urea/administration & dosage , Urea/analogs & derivativesABSTRACT
Our objective was to evaluate the short-term effects of calcium fructoborate (CFB) on gait, joint range of motion, serum inflammatory markers, and owner perception of pain in client-owned dogs. We used 59 osteoarthritic dogs with impairment, with dogs being randomly assigned to 4 treatments: placebo (60 mg fructose; = 15), low dose (69 mg CFB; = 14), high dose (127 mg CFB; = 14), or combination (69 mg CFB, 500 mg glucosamine hydrochloride and 200 mg chondroitin sulfate; = 16). Dogs up to 22.9 kg received 1 capsule/d, while dogs weighing 23 to 50 kg received 2 capsules/d. A physical examination, radiographs, goniometry measurements, gait analysis, blood sample collection, and a canine brief pain inventory questionnaire were performed on d 0 and 28. Change from baseline values were statistically analyzed among groups. After 28 d, dogs fed the low and high doses had an improved ( < 0.05) ability to rise from a lying position compared to placebo. Dogs fed the high dose also had a greater ( = 0.05) increase in soluble receptor for advanced glycation end products concentration than dogs fed the placebo. Sub-analysis of only large dogs (> 23 kg) showed that dogs fed the low dose had decreased ( < 0.05) pain severity score and pain at its worst compared to dogs fed the placebo. Large dogs fed the low dose also were shown to improve ( < 0.05) in their ability to rise from a lying position compared to dogs fed the placebo. Overall, CFB supplementation was well-tolerated and may aid in mitigating joint discomfort in dogs.
Subject(s)
Borates/administration & dosage , Dietary Supplements , Dog Diseases/diet therapy , Fructose/analogs & derivatives , Osteoarthritis/veterinary , Pain/veterinary , Animals , Borates/pharmacology , Calcium, Dietary/administration & dosage , Calcium, Dietary/pharmacology , Dog Diseases/pathology , Dogs , Double-Blind Method , Fructose/administration & dosage , Fructose/pharmacology , Gait , Inflammation/blood , Inflammation/veterinary , Joints/drug effects , Joints/pathology , Osteoarthritis/complications , Osteoarthritis/diet therapy , Osteoarthritis/pathology , Pain/drug therapy , Pain/etiology , Pain Measurement/drug effects , Random Allocation , Range of Motion, Articular/drug effectsABSTRACT
Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) and eosinophils produced primarily LTC4 In coincubations of these myeloid cells and epithelial cells, LTD4 became a prominent product. LTC4 released from the myeloid cells was further transformed by the epithelial cells in a transcellular manner. Formation of LTD4 was rapid when catalyzed by γ-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1ß, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation. Serine-borate complex (SBC), an inhibitor of GGT, inhibited conversion of LTC4 to LTD4 Unexpectedly, SBC also upregulated translocation of 5-lipoxygenase (LO) to the nucleus in Mono Mac 6 cells, and 5-LO activity. Our results demonstrate an active role for epithelial cells in biosynthesis of LTD4, which may be of particular relevance in the lung.
Subject(s)
Leukotriene C4/genetics , Leukotriene D4/genetics , Lung Neoplasms/immunology , gamma-Glutamyltransferase/genetics , A549 Cells , Arachidonate 5-Lipoxygenase/genetics , Arachidonate 5-Lipoxygenase/metabolism , Borates/administration & dosage , Eosinophils/immunology , Eosinophils/metabolism , Epithelial Cells/immunology , Epithelial Cells/metabolism , Exosomes/immunology , Exosomes/metabolism , Humans , Immunity, Cellular/genetics , Leukotriene C4/biosynthesis , Leukotriene D4/biosynthesis , Lung/immunology , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Myeloid Cells/metabolism , Myeloid Cells/pathology , Serine/administration & dosage , gamma-Glutamyltransferase/antagonists & inhibitorsABSTRACT
PURPOSE: To evaluate the effect of disinfection with sodium perborate or chlorhexidine (when combined with brushing) on the removal of biofilm in relined dentures. METHODS: Swabs were collected 48 hours after the relining procedure and at the follow-up time intervals of 7, 15, 30, 90, and 180 days. The dentures' surface roughness was measured at the same times. 45 subjects were randomly divided into three groups of 15 subjects each. The control group brushed with coconut soap and a soft toothbrush. The sodium perborate group followed the same procedure and also disinfected with sodium perborate solution for 5 minutes per day. The chlorhexidine group followed the control group procedure and disinfected with 2% chlorhexidine digluconate solution for 5 minutes per day. The number of colony forming units and the surface roughness were evaluated statistically by 2-way repeated-measure ANOVA (α = 0.05). RESULTS: The control group dentures exhibited similar levels of microbial cells throughout the experiment. However, after 15 days, no microbial growth was observed on the dentures for which either disinfection agent was used. There were no statistically significant differences in superficial roughness between the groups (P = 0.298). The disinfection agents used, combined with brushing, were able to remove the relined dentures' biofilm after 15 days of disinfection. Roughness was not a predominant factor in CFU reduction.
Subject(s)
Biofilms/drug effects , Dental Disinfectants/therapeutic use , Denture Bases/microbiology , Denture Rebasing , Aged , Borates/administration & dosage , Borates/therapeutic use , Chlorhexidine/administration & dosage , Chlorhexidine/analogs & derivatives , Chlorhexidine/therapeutic use , Cocos , Colony Count, Microbial , Dental Disinfectants/administration & dosage , Denture Cleansers/therapeutic use , Female , Follow-Up Studies , Humans , Male , Middle Aged , Phytotherapy/methods , Plant Preparations/therapeutic use , Surface Properties , Toothbrushing/instrumentation , Treatment OutcomeABSTRACT
Chemical mediators of inflammation (CMI) are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS)-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1ß and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS) in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1ß, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases.
Subject(s)
Borates/pharmacology , Boron/pharmacology , Cell Proliferation/drug effects , Immunologic Factors/pharmacology , Lipopolysaccharides/immunology , Lymphocytes/drug effects , Macrophages/drug effects , Animals , Borates/administration & dosage , Boron/administration & dosage , Cells, Cultured , Immunologic Factors/administration & dosage , Inflammation Mediators/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Lymphocytes/cytology , Lymphocytes/immunology , Macrophages/cytology , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/immunology , Tumor Necrosis Factor-alpha/immunologyABSTRACT
Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex "protective" effect against inflammatory response. CF is commercially available in the USA as a "nature-identical" complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C-reactive protein (CRP).
Subject(s)
Bone and Bones/drug effects , Borates/pharmacology , Cardiovascular Diseases/drug therapy , Fructose/analogs & derivatives , Bone and Bones/metabolism , Borates/administration & dosage , Borates/metabolism , Cardiovascular Diseases/metabolism , Fructose/administration & dosage , Fructose/metabolism , Fructose/pharmacology , Healthcare Disparities , HumansABSTRACT
Boron is an essential metalloid, which plays a key role in plant and animal metabolisms. It has been reported that boron is involved in bone mineralization, has some uses in synthetic chemistry, and its potential has been only recently exploited in medicinal chemistry. However, in the area of tissue engineering, the use of boron is limited to works involving certain bioactive glasses. In this study, we engineer poly(l-lactic acid) (PLLA) substrates with sustained release of boron. Then, we analyze for the first time the uniqueness effects of boron in cell differentiation using murine C2C12 myoblasts and discuss a potential mechanism of action in cooperation with Ca(2+). Our results demonstrate that borax-loaded materials strongly enhance myotube formation at initial steps of myogenesis. Furthermore, we demonstrate that Ca(2+) plays an essential role in combination with borax as chelating or blocking Ca(2+) entry into the cell leads to a detrimental effect on myoblast differentiation observed on borax-loaded materials. This research identifies borax-loaded materials to trigger differentiation mechanisms and it establishes a new tool to engineer microenvironments with applications in regenerative medicine for muscular diseases.
Subject(s)
Borates/administration & dosage , Calcium/metabolism , Delayed-Action Preparations/administration & dosage , Lactic Acid/chemistry , Myoblasts/cytology , Myoblasts/physiology , Polymers/chemistry , Animals , Borates/chemistry , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Line , Delayed-Action Preparations/chemical synthesis , Materials Testing , Mice , Muscle Development/drug effects , Muscle Development/physiology , Myoblasts/drug effects , PolyestersABSTRACT
OBJECTIVES: To investigate the whitening effects of different bleaching agents on teeth discoloured by different antibiotic combinations of ciprofloxacin and metronidazole with minocycline, doxycycline, amoxicillin or cefaclor. MATERIALS AND METHODS: Forty extracted bovine incisors were collected and discoloured with triple antibiotic pastes (TAP) with minocycline, doxycycline, amoxicillin and cefaclor throughout 30 days. The specimens were then randomly divided into two subgroups and each group received different bleaching materials: 35% hydrogen peroxide and sodium perborate. Spectrophotometric measurements were obtained on the buccal surfaces of the crown, firstly in the beginning, then on the 4th, 8th and 12th days after the placement of the bleaching materials. The acceptability threshold was set to 3.5. The ∆E values were calculated and the data was analysed using the repeated measures analysis of variance (P = .05). RESULTS: All the test groups induced colour changes exceeding the acceptability threshold 30 days after the antibiotic pastes were placed. The 35% hydrogen peroxide was more effective than sodium perborate in the whitening of discoloured teeth by antibiotic pastes (P = .001). The whitening effect after the 8th and 12th days was significantly more than after 4 days of treatment (P <.001). The discolouration caused by the TAP with minocycline and cefaclor showed greater whitening compared to the TAP with doxycycline and amoxicillin groups (P <.05). CONCLUSIONS: The whitening treatment effect of 35% hydrogen peroxide on teeth discoloured by antibiotic pastes seems to have significantly outperformed the sodium perborate treatment. Both bleaching agents were allowed to bleach the teeth gradually each day and the effects on the 8th and 12th days were superior to the one on the 4th day. CLINICAL RELEVANCE: The use of 35% hydrogen peroxide could be advantageous to bleach the teeth discoloured with antibiotic pastes compared to sodium perborate.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bleaching Agents/administration & dosage , Hydrogen Peroxide/administration & dosage , Tooth Bleaching/methods , Tooth Discoloration/chemically induced , Tooth Discoloration/drug therapy , Animals , Borates/administration & dosage , Cattle , Composite Resins , In Vitro Techniques , IridescenceABSTRACT
Calcium fructoborate (CFB) has been reported as supporting healthy inflammatory response. In this study, we assess the effects of CFB on blood parameters and proinflammatory cytokines in healthy subjects. This was a randomized, double-blinded, placebo-controlled trial. Participants received placebo or CFB at a dose of 112 mg/day (CFB-1) or 56 mg/day (CFB-2) for 30 days. Glucose, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), homocysteine, interleukin 1 beta (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1) were determined before and after supplementation. CFB-1 showed a reduction in blood levels of CRP by 31.3 % compared to baseline. CFB-1 and CFB-2 reduced LDL levels by 9.8 and 9.4 %, respectively. CFB-1 decreased blood homocysteine by 5.5 % compared with baseline, whereas CFB-2 did not have a significant effect. Blood levels of TG were reduced by 9.1 and 8.8 % for CFB-1 and CFB-2, respectively. Use of both CFB-1 and CFB-2 resulted in significantly reduced IL-6 levels, when compared within and between groups. IL-1ß was reduced by 29.2 % in the CFB-1 group. Finally, CFB-1 and CFB-2 reduced MCP-1 by 31 and 26 %, respectively. Our data indicate that 30-day supplementation with 112 mg/day CFB (CFB-1) resulted in a significant reduction of LDL, TG, TC, IL-1ß, IL-6, MCP-1, and CRP. HDL levels were increased, when compared to baseline and placebo. These results suggest that CFB might provide beneficial support to healthy cardiovascular systems by positively affecting these blood markers (ClinicalTrials.gov, ISRCTN90543844; May 24, 2012 ( http://www.controlled-trials.com/ISRCTN90543844 )).
Subject(s)
Borates/administration & dosage , C-Reactive Protein/metabolism , Chemokine CCL2/blood , Cholesterol/blood , Fructose/analogs & derivatives , Interleukin-1beta/blood , Interleukin-6/blood , Lipoproteins, LDL/blood , Triglycerides/blood , Adult , Double-Blind Method , Female , Fructose/administration & dosage , Humans , Male , Middle Aged , Time FactorsABSTRACT
UNLABELLED: Everyone wants whiter teeth to make them feel younger and to provide beautiful smiles with the accompanying increase in self-esteem. Bleaching is an established, simple, cost-effective and conservative method for improving the color of the discolored teeth. AIM: The aim of this in vitro study was to compare the bleaching efficacy of 10% carbamide peroxide, 10% hydrogen peroxide and 2g sodium perborate as bleaching agents on the artificially discolored human primary maxillary central incisors. MATERIALS AND METHODS: Forty extracted human primary central incisors with intact crowns were selected for the study. Pulpectomy was performed and each tooth was artificially stained with 2 ml of fresh human blood and centrifuged. --The teeth were randomly divided into four experimental groups of 10 teeth each and the baseline color evaluation was performed. 0.04 ml of the bleaching agent is syringed into the access cavity of the tooth and, in the control group, 0.04 ml of distilled water was syringed into the access cavity and it was sealed with IRM and placed at 37°C in an incubator throughout the experiment. The color of the bleached teeth was determined at 0, 7 and 14 days. The data obtained were analyzed using ANOVA and Turkey's test. RESULTS: There was statistical significance (P = 0.00) among the carbamide peroxide, sodium perborate, hydrogen peroxide and control groups after 7 and 14 days and a significance of P = 0.013 among the carbamide peroxide, sodium perborate and hydrogen peroxide after two bleaching sessions (day 14) was seen. CONCLUSIONS: The bleaching efficacy of 10% hydrogen peroxide gel was more effective than 10% carbamide peroxide and sodium perborate in bleaching the artificially discolored primary teeth.