Transforaminal and systemic diffusion of an active agent from a zinc oxide eugenol-based endodontic sealer containing hydrocortisone-in an in vivo model.

OBJECTIVES: This study aimed to quantify in vivo the release of hydrocortisone acetate (HCA) contained in a zinc oxide eugenol-based endodontic sealer, in various tissues. MATERIALS AND METHODS: Roots of human teeth, shaped with One Shape single file and sealed with Endomethasone N, previously radiolabelled with tritium (3H-HCA), were implanted in the back of 24 mice. Mice were sacrificed at 2, 8, 24, and 48 h to evaluate and quantify the amount of radioactivity in subcutaneous tissues surrounding the apex (periapical-like) of the implanted teeth, blood, spleen, kidneys, liver, and urine. RESULTS: Radioactivity was released from the apex of the tooth into the periapical-like tissues with a peak measured at 2 h post-implantation (2.25% of the initial radioactivity/g). This quantity decreased significantly over time between 2 h and each time points. Radioactivity was still measured up to 48 h in the periapical-like tissues (0.42% of the initial radioactivity). The same pattern of kinetic was observed for all organs. The total quantity of radioactivity significantly decreased over time from 4.36% measured 2 h post-implantation to 0.74% at 48 h. Finally, about 10% of the initial radioactivity from Endomethasone N used to fill the root canal was retrieved after 48 h in the urine. CONCLUSIONS: This study demonstrated that radioactive-HCA from Endomethasone N can diffuse through the apex of the root canal and follow a classical pharmacokinetics. CLINICAL RELEVANCE: This mouse model shows that radioactive-HCA can diffuse through the apex and do not accumulate in periapical-like tissues and organs.

The comparative cytotoxic effects of different local anesthetics on a human neuroblastoma cell line.

BACKGROUND: Although local anesthetics (LAs) are generally accepted as being safe, incidental neuronal damage has been reported for all LAs in humans. Therefore, in this study, we compared the dose corresponding to 50% cell lethality (LD50) of articaine, lidocaine, mepivacaine, bupivacaine, prilocaine, and ropivacaine in human neuroblastoma cells. METHODS: Undifferentiated SH-SY5Y cells were exposed for 20 minutes to different concentrations of each LA. Metabolic activity of viable cells was assessed by a cell viability test with a tetrazolium dye (WST-1) followed by optical density quantification. LD50 was determined by extrapolation of curve response. RESULTS: As expected, all LAs induced cell death in a concentration-dependent manner. The bupivacaine, lidocaine, prilocaine, mepivacaine, articaine, and ropivacaine LD50 were 0.95 ± 0.08, 3.35 ± 0.33, 4.32 ± 0.39, 4.84 ± 1.28, 8.98 ± 2.07, and 13.43 ± 0.61 mM, respectively, after 20 minutes of incubation on SH-SY5Y cells. Ropivacaine LD50 was significantly different from the bupivacaine, lidocaine, mepivacaine, and prilocaine LD50 (all P ≤ 0.009). No significant difference was obtained between ropivacaine and articaine LD50 and between prilocaine, lidocaine, and mepivacaine LD50. Articaine LD50 was significantly different from lidocaine LD50 (P = 0.03). Bupivacaine LD50 was significantly lower compared with all LAs (all P ≤ 0.003). CONCLUSIONS: LA neurotoxicity was tested in a validated in vitro model SH-SY5Y, a human neuroblastoma cell line. Three groups of LAs were identified in terms of toxicity: (1) the less (ropivacaine, articaine); (2) medium (mepivacaine, prilocaine, lidocaine); and (3) the high (bupivacaine). Among dental anesthetics, articaine is the least neurotoxic in SH-SY5Y cells.

Increased glucose excursion in cystic fibrosis and its association with a worse clinical status.

BACKGROUND: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. METHODS: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. RESULTS: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV(1)). CONCLUSION: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.

Bovine lactoferrin improves bone status of ovariectomized mice via immune function modulation.

We have previously shown that bovine lactoferrin (bLF) supplementation can have a beneficial effect on postmenopausal bone loss by modulating bone formation and resorption. A direct effect of bLF on bone metabolism is support by its presence in mice blood. Moreover we know that LF plays a key role in innate immunity and recent studies have shown its ability to modulate adaptive immunity. In particular bLF ingestion prevents recruitment and activation of immune cells at inflammatory sites. We propose that LF through its ability to modulate maturation and differentiation of leucocytes can participate to abolish the deregulation induced by estrogen deficiency on T cells. This study evaluated the effects of bovine lactoferrin on immune function in ovariectomized mice. We investigated whether bLF ingestion could prevent bone loss via modulation of immune function. Three-month-old female C3H mice were either ovariectomized or sham-operated and fed for 1, 2 or 4 months with a control diet (AIN-93M) or the same diet including 10g bLF/kg diet. Bone mineral density was determined using a Lunar Piximus densitometer. The immune parameters were assessed by flow cytometry. In addition, Real-Time PCR was performed to quantify TNFα expression and plasma cytokines were measured at 4 months with Luminex. Ovariectomy induced significant changes on bone parameters and increased recruitment of macrophages, dendritic cells, and B and T cells associated with T lymphocyte activation in bone marrow. Compared to the control diet, ingestion of bLF-enriched diet for 2 months prevented T cell activation and restored dendritic and B cell populations in the bone micro-environment in ovariectomized mice. Furthermore, TNFα expression in bone was decreased by bLF supplementation after 2 and 4 months. Similarly, a decreased plasma level of TNFα was observed concomitantly to an increase of IL-10 level. In conclusion, these experiments suggest that bLF can mediate the prevention of lymphocyte activation and cytokine release in the bone micro-environment. Dietary bLF supplementation could have a beneficial effect on postmenopausal bone loss by modulating immune function.

Oral bovine lactoferrin improves bone status of ovariectomized mice.

The aim of the present study was to evaluate the effect of dietary lactoferrin on bone metabolism in vivo using a postmenopausal animal model. We investigated whether bovine lactoferrin (bLF) ingestion could prevent bone loss in ovariectomized mice. Twelve-week-old female C3H mice either ovariectomized or sham operated were fed for 27 wk with the control diet (AIN-93M with 140 g of total milk protein as a protein source per kg of diet). Four groups of ovariectomized mice received diets including different concentrations of bLF (1, 5, 10, or 20 g of total milk protein were replaced by bLF). Ovariectomy induced a decreased uterine weight and a smaller gain of bone mineral density. Immunoreactive bLF was detected in the peripheral blood, and its concentration was related to the amount of bLF ingestion. bLF supplementation to the diet improved bone mineral density (BMD) and femoral failure load in a dose-dependent manner. We confirmed the direct effects of bLF in vitro using established and primary cultures of murine bone cells. Addition of bLF to the culture medium at a concentration of between 1 and 1,000 microg/ml stimulated both cell growth and differentiation of osteoblastic MC3T3 cells while inhibiting the growth of preosteoclastic RAW 267.4 cells. In primary culture of mixed bone cells, an enhanced osteoblast differentiation was associated with an inhibition of osteoclast differentiation at lower bLF concentrations (1-10 microg/ml). In conclusion, these findings suggest that dietary lactoferrin supplementation can have a beneficial effect on postmenopausal bone loss by modulating bone formation and resorption.