Effect of Dentin Conditioning with Intracanal Medicaments on Survival of Stem Cells of Apical Papilla

Introduction

Regenerative endodontics is a valuable treatment modality for immature teeth with pulpal necrosis. A common feature in regenerative cases is the use of intracanal medicaments. Although these medicaments are chosen because of their antibacterial properties, their enduring effect on dentin (conditioning) and the subsequent impact on stem cell survival has never been evaluated. In this study, we hypothesized that triple antibiotic paste (TAP), double antibiotic paste (DAP), or Ca(OH)₂ has an indirect adverse effect on the survival of stem cells of apical papilla (SCAP) by dentin conditioning.

Methods

Human dentin disks were created with a standardized root canal diameter of 3.2 mm. The disks were then exposed to either TAP or DAP (at concentrations of 1 mg/mL or 1000 mg/mL), Ca(OH)₂ (Ultracal), or Hank's balanced salt solution for 7 or 28 days. Next, the medicaments were removed with copious irrigation, followed by placement of SCAP in a Matrigel scaffold in the lumen of the disks. The bioengineered constructs were cultured for 7 days, followed by determination of cellular viability by using the CellTiter-Glo luminescence assay. Data were analyzed using 1-way analysis of variance with Bonferroni post hoc test.

Results

Exposure of dentin to TAP or DAP at 1000 mg/mL resulted in no viable SCAP, whereas the use of these medicaments at 1 mg/mL had no adverse effect on cell viability. In contrast, Ca(OH)₂ treatment significantly increased SCAP survival and proliferation when compared with the control group.

Conclusions

Dentin conditioning with TAP and DAP at commonly used clinical concentration (approximately 1000 mg/mL) alters dentin in such a way as to prevent SCAP survival. This lethal indirect effect of both TAP and DAP can be largely avoided if these medicaments are used at the 1 mg/mL concentration. Conversely, dentin conditioning with Ca(OH)₂ promotes SCAP survival and proliferation.     

Cortical Cells That Migrate Beyond Area Boundaries: Characterization of an Early Neuronal Population in the Lower Intermediate Zone of Prenatal Rats

Studies of the early development of the mammalian cerebral cortex have revealed that the earliest generated neurons that form the primordial plexiform layer (also called preplate or marginal zone) distribute among layer I and layer VII (subplate). By means of bromodeoxyuridine labelling of cells becoming postmitotic, we have found evidence that, in the rat, an additional group of neurons of the primordial plexiform layer remains in the close vicinity of the ventricular zone. This finding, in line with the proposal by Marín-Padilla ( Z Anat. Entwicklungsgesch. , 134 , 117-145, 1971), implies that the primordial plexiform layer suffers a tripartition after the formation of the cortical plate and of the intermediate zone (the latter soon becomes the embryonic white matter). Thus, primordial plexiform layer derivatives are in layer I, layer VII (subplate) and in the lower part of the embryonic white matter. This early generated neuronal population is also revealed with an antibody that recognizes the larger (67 kDa) isoform of glutamic acid decarboxylase (Kaufman et al., Science , 232 , 1138-1140, 1986). This is in accord with the earlier finding of a GABA-containing cell population showing a similar spatiotemporal distribution. The early generated neurons of the embryonic white matter migrate tangentially and, in early postnatal animals, are found as interstitial cells in the medial regions of the subcortical white matter and at the midline in the corpus callosum. At caudal levels, similar cells invade the subpyramidal strata of the developing hippocampus. This tangential migration might explain the tangential dispersion of neural cell clones described in recent studies of cell lineage in the cerebral cortex.     

cis-Platinum and 5-fluorouracil as initial therapy in advanced epidermoid cancers of the head and neck

A total of 44 patients with previously untreated Stage IV squamous cell carcinomas of the head and neck were treated with a combination of cis-platinum (100 mg/sq m) and 96-hour infusion of 5-fluorouracil (5-FU) (1,000 mg/sq m/day) in two courses or with cis-platinum (100 mg/sq m) and 120-hour infusion of 5-FU (1,000 mg/sq m/day) in three courses. In the 26 patients receiving the two course regimen, the tumor response rate was 88.5%. In five of the 26 patients complete disappearance of the tumor was achieved; partial remission was obtained in 18 of 26 patients. The main side effects were nausea and vomiting (70%), leukopenia (27%), and mild-to-moderate renal toxicity (27%). In the 18 patients who received the three course regimen of 5-FU and cis-platinum, there were 11 (61%) complete responses, 6 (33%) partial responses, and 1 (6%) minimal response. The incidence of complete response was increased with each course given. No added toxicity was observed with surgery or radiotherapy.     

Acceptability of the Contraceptive Vaginal Ring by rural and urban population in two Latin American countries

A study of the field acceptability of the Contraceptive Vaginal Ring (CVR) was carried out in rural, small town and urban slum clinics in four locations, two in Brazil and two in the Dominican Republic (D.R.). The CVR was offered as a new method in the clinics and described as similar to the pill but placed in the vagina for three weeks each month with a one-week rest interval. Follow-up surveys were carried out in the four locations at the end of the experimental period. Three, eight, nine and 12.5% of the total acceptors in each of the 4 locations chose the CVR. The acceptance rate fell after the first five months but recovered during the second year. The acceptance rate was much higher in three rural clinics where the nurses themselves used the ring. The follow-up surveys showed that the fact that the ring is placed and kept in the vagina without removal for a prolonged period was the most important attribute of the method and played a large role in women's reactions to it. Anticipated use-related problems were the most prominent reason given by pill users for not choosing the ring, however ease of use was named as the “most liked” characteristic by 55% of ring users. Women tended to remove the ring for intercourse and washed it frequently, often with detergents, thus illustrating their concern with “cleanliness” of an object kept within a body cavity for long periods of time.     

Dual mechanism of mangiferin protection against iron-induced damage to 2-deoxyribose and ascorbate oxidation.

We studied mangiferin effects on the degradation of 2-deoxyribose induced by Fe(III)-EDTA/citrate plus ascorbate, in relation to ascorbate oxidation (measured at 265 nm). Results revealed that mangiferin was equally effective in preventing degradation of both 15 and 1.5 mM 2-deoxyribose. At a fixed Fe(III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of mangiferin. Interestingly, mangiferin strongly stimulated Fe(III)-EDTA ascorbate oxidation, but inhibited it when citrate was used as iron co-chelator. Mangiferin stimulated O2 consumption due to Fe(II) (formed by Fe(III) ascorbate reduction) autoxidation when the metal ligand was EDTA, but inhibited it when citrate was used. These results suggest that mangiferin removes iron from citrate, but not from EDTA, forming an iron-mangiferin complex that cannot induce ascorbate oxidation effectively, thus inhibiting iron-mediated oxyradical formation. Taken together, these results indicate that mangiferin works mainly by a mechanism different from the classical hydroxyl radical scavengers, keeping iron in its ferric form, by complexing Fe(III), or stimulating Fe(II) autoxidation.     

Carcinoma of prostate metastatic to breast

Clinically diagnosed breast metastasis from prostatic carcinoma is rare. Primary breast carcinoma in patients with prostatic primary is also uncommon. Four patients who presented with breast malignancies in the course of their prostatic carcinoma are described. All but one of them had diffuse metastatic disease. Three of them were on estrogens at the time breast malignancy was diagnosed. Difficulties always arise in differentiating primary lesions from metastasis clinically and histopathologically. The development of histochemical methods for acid phosphatase, and the newest indirect immunofluorescent antibody technique, used in one of our patients, helped in making the differentiation between primary lesion and metastatic disease. Diagnosis of prostatic carcinoma metastatic to breast carries a poor prognosis, and may be an indication for aggressive therapy.     

Is the cyclic GMP system underestimated by intensive care and emergency teams?

At present, the clinical management inflammatory vasoplegia associated to sepsis or anaphylaxis is symptomatic. Volume is expanded by means of administration of fluids, and low blood pressure is managed by means of administration of positive inotropes and vasoconstrictors. This therapeutic approach is mainly associated to the cyclic AMP (cAMP) and, many times the circulatory shock is refractory to high amines concentrations. However, beside of cAMP-dependent vasoreactivity mechanisms there are other two known vasoplegia involved mechanisms: cyclic GMP (cGMP) and hyperpolarization that is less clinically considered. Also, it is possible to speculate about 'probable vasopressin deficiency'. Methylene blue (MB) is the most useful and clinically safe cGMP blocker. We propose a decision tree for diagnosis and institution of this therapeutical approach many times underestimate by intensive care and emergency teams.