Magnetic hyperthermia treatment (MHT) using magnetic nanoparticles (MNPs) has emerged as a novel strategy for cancer therapy. However, one concern of traditional hyperthermia is that it may affect both normal and tumor tissues. The current study therefore aimed to examine the antitumor effects of locally injecting magnetic nanoparticles encapsulated in super carbonate apatite (sCA), an efficient drug delivery system in combination with MHT. This study also investigated the effects of this combination on magnetic particle imaging (MPI).
First, the amount of iron encapsulated into the sCA was determined, after which a phantom experiment was performed to examine the pH sensitivity of MNPs encapsulated in the sCA (sCA-MNPs) or MNPs (pH 6.4–7.4) using an MPI scanner. Thereafter, an in vitro experiment involving the quantification of iron uptake in sCA-MNP-, MNP-, and sCA-treated Colon-26 cells and an in vivo experiment involving an MPI study after MNP or sCA-MNP injection were conducted. The antitumor effects of the following five groups were compared: Control, MNPs, MNPs + MHT, sCA-MNPs, and sCA-MNPs + MHT.
Our findings showed that the maximum encapsulation efficiency of iron into the sCA was 29.5% ± 1.59%. The phantom experiment in the sCA-MNP group revealed that the MPI signal was highest during the low-pH condition and decreased during the high-pH condition. However, the MPI signal in the MNP group remained unaffected. Our results showed that sCA-MNPs were better incorporated into the cells compared to MNPs and sCA alone. The in vivo experiment showed that MPI values increased immediately after to 4 h after injection in the sCA-MNP group but did not increase in the MNPs group. The sCA-MNP + MHT group showed stronger antitumor effects compared to the MNP + MHT group 1 to 5 days after MHT.
Combination therapy with sCA-MNPs and MHT may be useful for cancer treatment, with sCA-MNPs being successfully imaged through MPI.
Oral dyskinesia is a condition in which oral organs exhibit involuntary movements. The aim of this study was to determine the contribution of oral sensation to the control of oral dyskinesia using an animal model that exhibits vacuous tongue movements after systemic administration of dopamine (DA) agonists.
Adult male Sprague-Dawley rats were used in all experiments. Tongue movement was elicited in a freely moving rat model by systemic administration of a mixture of the D1 receptor agonist SKF38393 and the D2 receptor agonist quinpirole. The number of tongue protrusions was calculated from electrical myographic data obtained from the genioglossal muscle. Extracellular concentrations of DA and serotonin (5-HT) in the nucleus accumbens were determined using in vivo microdialysis. To investigate the effects of oral sensation on vacuous tongue movement, deafferentation of the palatal mucosa was performed, and the above experiments were repeated.
The hyperactivity of tongue protrusion induced by administration of SKF38393 and quinpirole was significantly inhibited by palatal deafferentation. Palatal deafferentation also significantly reduced the increase in extracellular 5-HT concentration in the nucleus accumbens produced by administration of DA agonists.
These results support the important contribution of oral sensation to vacuous tongue protrusion in a rat model of oral dyskinesia.
Inward rectification is a common membrane property that controls subthreshold and firing behavior such as resonance, repetitive firing and intrinsic bursting activities in mesencephalic trigeminal (Mes V) neurons, which regulate oral-motor activities. Endogenously released neurotransmitters and extracellular ionic environment and homeostasis modulate the fast (IKIR) and slow (Ih) inward rectifying currents underlying this membrane property. The present study evaluates the influence of zinc deficiency, which causes alteration in feeding behavioral characteristics, on this membrane property including IKIR and Ih in neonatal rat Mes V neurons.
Sprague–Dawley rats (postnatal days 10–12) were fed either a normal diet (CT) or a zinc-deficient diet (ZD). Whole-cell patch-clamp recordings were obtained from Mes V neurons in coronal brain slices and inward currents in response to hyperpolarizing voltage steps were recorded under modified ACSF solution to specifically isolate IKIR and Ih.
Depolarizing voltage sag in response to hyperpolarizing current pulses were suppressed in the ZD group under current-clamp recording. Also, there were no differences in amplitude and current density of IKIR between the two groups, while the current density in Ih of the ZD group was substantially lower under voltage-clamp recording. The activation curve for Ih including half-maximal activation voltage was shifted to more hyperpolarized potential and both fast and slow time constants for Ih activation were higher in the ZD group than those in the CT group.
Zinc deprivation modulates slow inward rectifying current, Ih by decreasing the maximum conductance and shifting the gating properties of activation in Mes V neurons.
The purpose of this study was to assess the activation of stem cells in bone marrow after administering insulin to rats. The prompt proliferation of stem cells and differentiation into osteoblasts or odontoblasts are necessary and desirable processes for bone or tooth regeneration. There may be factors that promote these processes effectively and insulin was hypothesized as one such factor. Calcified nodule formation by bone marrow cells was quantified. Six 5-week-old male Fischer 344/N Slc rats were used. The insulin solution for injection was prepared at a concentration of 1 U/mL in PBS (-) from the formulation dry with potency at 27.5 units/mg or more. The solution (0.5 U) was injected into the dorsal subcutaneous tissue of rats in 2-day intervals for 11 days. The other rats that were not administered insulin subcutaneously were used as a control group. After an 11- day injection period, bone marrow cells were removed from the femur. The cells collected from rats injected with insulin subcutaneously were cultured in medium containing β-glycerophosphate with or without dexamethasone and ascorbic acid. Conspicuously formed calcified nodules were decalcified in 10% formic acid. Two-way unrepeated ANOVA followed by post hoc analysis with Tukey-Kramer's test was performed. Differences of p < 0.01 were considered significant. A significant amount of Ca2+ was found in culture of bone marrow cells from the rats injected with insulin. With rBMCs from insulin-injected rats, 196.34 ± 15.49 μg/mL of Ca2+ was produced when Dex was added to the medium. Without insulin injection, the cells cultured with Dex produced 126.34 ± 1.87 μg/mL. It is concluded that bone marrow cells obtained from rats with systemic insulin administration exhibited a high ability to form calcified nodules.
The intense photoirradiation-induced influence of a photosensitizer, camphorquinone (CQ), contained in light-cured composite resin applied on intraoral tissue is of concern. The difference in cell viability between groups treated with and without light-irradiated culture medium containing CQ was investigated using 3T3 cells, which were used according to the OECD phototoxicity guidelines. A large difference in cell viability was noted between the photoirradiation and non-photoirradiation groups within a concentration range of 0.3125∼2.5 mg/mL. The influence of phototoxicity was previously not considered in the dental field, but as restoration methods applying intense photoirradiation in the oral cavity, such as light-cured composite resin, are now widely used clinically, the biological influence of intense photoirradiation, even though applied only for a short time, on intraoral tissue must be considered.
The viability of cells exposed to chemicals may differ depending on the degree of differentiation. In the present study, we used a murine embryonic stem (ES) cell line, ES-D3, which does not require feeder cells in culture, to compare the viability of undifferentiated and differentiated cells following exposure to a chemical. Differentiated cells were maintained at the first (P1) and second passages (P2), and cells were exposed to nano-sized titanium dioxide (nano-TiO2). There were no significant differences in the viability of cells among the three differentiation stages; however, undifferentiated cells had slightly lower viability than differentiated cells. There was no significant difference in cell viability between differentiated cells at P1 and P2. Our findings were based on the response of cells to nano-TiO2; thus, it should be noted that other chemicals may have different effects. Our study also suggests that undifferentiated ES cells are more sensitive to chemicals; therefore, they may be useful to evaluate the cytotoxicity of nano- and sub-micron-sized chemicals.
Surface-assisted laser desorption / ionization mass spectroscopy (SALDI-MS) in negative mode of various amino acids with commercial TiO2 nanoparticles as the DI assisting material is reported. SALDI-MS gives clear spectra of these low molecular weight negative ions, such as drugs and bio-related organic compounds. With commercially available TiO2 nanoparticles, 20 common amino acids used could be clearly detected as [M-H]- molecular ions. The ion intensity of [M-H]- molecular ions is well linear correlated with the gas-phase acidity but less correlation with the hydrophobicity. But the concentration of the amino acids on the TiO2 nanoparticle surface also affected the ion intensity.
C60 (fullerene) nanomaterials have raised health concerns. In our experiment, insoluble C60 fullerene was adsorbed with cells on the surface of glass fibers without a solvent. Cell viability was examined in conventional two- and glass fiber-based three-dimensional cultures. As a result, C60 fullerene had no significant effect on the cell viability in both two- and three-dimensional cultures. No significant difference was noted between these cultures. Biosafety assays for materials, such as C60 fullerene, insoluble in culture medium, should be further investigated.
We report an unusual case of tophaceous pseudogout that appeared in the right temporomandibular joint (TMJ) accompanied with painless swelling at periauricular region of a Japanese elderly man. Radiographic examination including computed tomographic images revealed an exophytic radiopaque lesion with clear boundaries in the right peri-condylar region. Surgical resection was employed, and a microscopic examination of the surgical specimen showed the deposition of basophilic rhomboidal crystals around which foreign body reactions including multinucleated giant cells and chondrogenicity were localized. Aggregates of rhomboid crystalline deposits were exposed under polarized light. Further elemental analysis confirmed the involvements of Ca and P and positive birefringence under a polarizing microscope, which helped in the histopathological diagnosis of tophaceous pseudogout.
Nanomaterials may be combined in many dental component materials in the future. Moreover, products prepared with nanomaterials alone are rarely developed, and nanomaterials are likely to be added to conventional chemical substances. However, there are no data on changes in the toxicity caused by interaction between nanomaterials and dissolved chemical substances. Thus, a trace amount of nano-zinc oxide, which has no effect on cell viability, was mixed with culture medium to examine the cytotoxicity level of Bis-GMA, which is routinely used as a dental monomer. As a result, the interaction between nano-zinc oxide and Bis-GMA slightly increased the cytotoxicity of Bis-GMA. Furthermore, we were clarified that the cytotoxicity levels slightly changed in the presence of a very small amount of nano titanium dioxide or nano zinc oxide compared with those in the absence of nanomaterials, but the changes were not marked. Those finding may contribute to future studies on the cytotoxicity of nanomaterials. Some of these discoveries may contribute to future research on the combined toxicity of nanomaterials.