Comparative efficacy of endodontic medicaments and sodium hypochlorite against Enterococcus faecalis biofilms.

BACKGROUND: Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy of commonly used medicaments against E. faecalis cultured as a biofilm on dentine substrate. METHODS: An E. faecalis biofilm was established on human dentine slices using a continuous flow cell. Each test medicament (Ledermix, Ca(OH)2 , Odontopaste, 0.2% chlorhexidine and 50:50 combinations of Ledermix/Ca(OH)2 and Odontopaste/Ca(OH)2 ) was introduced into the flow cell and biofilms were harvested and quantitated by determining cellular protein. Cellular viability was determined using serial plating and the number of colony-forming units was normalized against cellular protein to allow treatment protocols to be compared. Qualitative scanning electron microscopy analyses of the biofilm were performed after a 48-h exposure to each test agent. RESULTS: Sodium hypochlorite achieved total bacterial elimination. Ledermix and Odontopaste had no significant effect on the E. faecalis biofilm. Ca(OH)2 and 50:50 combinations of Ca(OH)2 /Ledermix or Ca(OH)2 /Odontopaste reduced the viability by more than 99% while 0.2% chlorhexidine reduced bacterial numbers by 97%. CONCLUSIONS: Sodium hypochlorite remains the gold standard for bacterial elimination in root canal therapy. However, Ca(OH)2 in isolation and combined with Ledermix, and Odontopaste was highly effective in reducing bacterial viability.

Variable patterns of ectopic mineralization in Enpp1asj-2J mice, a model for generalized arterial calcification of infancy.

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular system. The classical forms of GACI are caused by mutations in the ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a spontaneous mutation in the Enpp1 gene has been characterized as a model for GACI. These mutant mice develop ectopic mineralization in skin and vascular connective tissues as well as in cartilage and collagen-rich tendons and ligaments. This study examined in detail the temporal ectopic mineralization phenotype of connective tissues in this mouse model, utilizing a novel cryo-histological method that does not require decalcification of bones. The wild type, heterozygous, and homozygous mice were administered fluorescent mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and 11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and examined for progression of mineralization. The results revealed differential timeline for disease initiation and progression in various tissues of this mouse model. It also highlights the advantages of cryo-histological fluorescent imaging technique to study mineral deposition in mouse models of ectopic mineralization disorders.

Systemic and local applications of steroids in endodontics: an update review.

Up to 80% of endodontic patients who report with preoperative pain continue to experience some level of pain following the endodontic procedure. Various classes of drugs have been studied for the management of post-treatment endodontic pain. Since endodontic pain is often associated with chronic inflammation, the presence of bacterial by-products, influx of primed immune cells and activation of the cytokine network and other inflammatory mediators, pain may be reduced by administration of glucocorticoid steroids. The aim of this paper is to review the pharmacology and mechanisms of actions of steroids as well as their indications for endodontics, contraindications, dosages and side-effects.

On the local applications of antibiotics and antibiotic-based agents in endodontics and dental traumatology.

Antibiotics are a valuable adjunctive to the armamentarium available to health professionals for the management of bacterial infections. During endodontic treatment and when managing trauma to the teeth, antibiotics may be applied systemically (orally and/or parenterally) or locally (i.e. intra-dentally via irrigants and medicaments). Due to the potential risk of adverse effects following systemic application, and the ineffectiveness of systemic antibiotics in necrotic pulpless teeth and the periradicular tissues, the local application of antibiotics may be a more effective mode for delivery in endodontics. The aim of this article was to review the history, rationale and applications of antibiotic-containing irrigants and medicaments in endodontics and dental traumatology. The search was performed from 1981 to 2008 and was limited to English-language papers. The keywords searched on Medline were 'Antibiotics AND endodontics', 'Antibiotics AND root canal irrigation', 'Antibiotics AND intra-canal medicament', 'Antibiotics AND Dental trauma' and 'Antibiotics AND root resorption'. The reference section of each article was manually searched to find other suitable sources of information. It seems that local routes of antibiotic administration are a more effective mode than systemic applications. Various antibiotics have been tested in numerous studies and each has some advantages. Tetracyclines are a group of bacteriostatic antibiotics with antibacterial substantivity for up to 12 weeks. They are typically used in conjunction with corticosteroids and these combinations have anti-inflammatory, anti-bacterial and anti-resorptive properties, all of which help to reduce the periapical inflammatory reaction including clastic-cell mediated resorption. Tetracyclines have also been used as part of irrigating solutions but the substantivity is only for 4 weeks. Clindamycin and a combination of three antibiotics (metronidazole, ciprofloxacin and minocycline) have also been reported to be effective at reducing bacterial numbers in the root canal systems of infected teeth.

The effects of Ledermix paste on discolouration of mature teeth.

AIM: The aims of this study were to: (i) investigate the effects of Ledermix paste as an intracanal medicament on discolouration of mature teeth, (ii) examine whether the discolouring effects were related to the method of application, and (iii) examine the effects of sunlight upon discolouration of mature teeth. METHODOLOGY: The root canals of 45 mature extracted human teeth were prepared and filled with either Ledermix paste, calcium hydroxide [Ca(OH)2], or saline. In group 1, Ledermix paste was placed apical to the cemento-enamel junction (CEJ), whilst in groups 2 and 3 the paste filled the entire pulp chamber and root canals. In group 4, a Ca(OH)2 and methyl cellulose paste and, in group 5, saline (control) were allowed to fill the pulp chamber and the root canals. Group 3 teeth were kept in the dark and the other groups were exposed to indirect sunlight for 12 weeks. RESULTS: After 12 weeks, sunlight exposure had caused dark grey-brown staining of the teeth in the Ledermix groups, but this did not occur when the teeth were kept in the dark. More severe staining was noted when Ledermix paste filled the pulp chamber than when the paste was restricted to below the CEJ. CONCLUSIONS: It was concluded that Ledermix paste may cause discolouration of teeth. Such effects can be minimized if placement of the paste is restricted to below the gingival margin. Clinicians should ensure that Ledermix paste is not left on the walls of access cavities.

The effects of Ledermix paste on discolouration of immature teeth.

AIM: The aims of this study were to: (i) investigate the effects of Ledermix paste as an intracanal medicament on discolouration of immature teeth, (ii) examine whether the discolouring effects were related to the method of application, (iii) examine the effects of sunlight upon discolouration of immature teeth and (iv) compare the degree of discolouration between mature and immature teeth. METHODOLOGY: The root canals of 45 immature extracted human teeth were prepared and filled with either Ledermix paste, calcium hydroxide [Ca(OH)2], or saline. In group 1, Ledermix paste was only placed apical to the cemento-enamel junction (CEJ) whilst in groups 2 and 3, the paste filled the entire pulp chamber and the root canals. In group 4, Ca(OH)2 paste and in group 5, saline (control) were allowed to fill the pulp chamber and the root canals. Group 3 teeth were kept in the dark and the other groups were exposed to daylight for 12 weeks. RESULTS: After 12 weeks, sunlight exposure had caused dark grey-brown staining in the Ledermix groups but this did not occur when the teeth were kept in the dark. More severe staining was noted when Ledermix paste filled the pulp chamber than when the paste was restricted to below the CEJ and when teeth were exposed to sunlight. When compared to the results of a similar study using mature teeth, the results were similar but the immature teeth were more severely stained than the mature teeth. The Ca(OH)2 paste caused an increase in lightness and yellowness in immature teeth. CONCLUSION: It was concluded that Ledermix paste may cause discolouration of immature teeth. Such effects can be minimized if placement of the paste is restricted to below the gingival margin. Clinicians should ensure that Ledermix paste is not left on the walls of access cavities, especially in immature teeth.

Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment.

To study the anti-resorptive effects of zoledronate and pamidronate on growing long bones we have performed a histomorphometric analysis of the three regions of the proximal tibial cancellous bone of bone formed before, during, and after drug treatment. Male rats (190-220 g) were treated subcutaneously for 10 days with zoledronate (0.028-2.8 microg/kg) or pamidronate (3.7-370 microg/kg) and sacrificed 5 days later. To delineate the three regions of cancellous bone, and for dynamic bone histomorphometry, calcein and demeclocycline were injected at various times. Both bisphosphonates caused a dose-dependent suppression of cancellous bone turnover and resorption to produce an increase in cancellous bone, but zoledronate was 100 times more potent than pamidronate. The increase in the bone amount and connectivity was more pronounced in the bone formed during treatment where transient bone resorption and normal bone formation led to a positive bone balance. In the bone formed before treatment, inhibition of bone resorption associated with reduced bone formation produced a net gain in amount of bone. Although both bone regions showed a positive bone balance, more bone accumulated in the bone formed during treatment probably because its trabecular bone surface was three times greater. In the primary spongiosa formed after treatment, a moderate increase in the bone amount and connectivity was observed only at the highest dose of both bisphosphonates. The bone formed before, during, and after treatment with bisphosphonates responds differently due to differences in bone architecture, rates of modeling and remodeling, and period of drug exposure.

Atrial natriuretic peptide in patients with the syndrome of inappropriate antidiuretic hormone secretion and with diabetes insipidus.

To examine a possible role for atrial natriuretic peptide (ANP) in water and sodium metabolism disturbances associated with abnormal vasopressin (AVP) secretion, we measured plasma ANP concentrations in 15 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in 17 patients with central diabetes insipidus (DI). The mean plasma ANP concentration (30.2 +/- 10.4 pmol/L) in SIADH patients who had hyponatremia, plasma hypoosmolality, hyperosmolar urinary compared to plasma sodium levels, and increased plasma AVP levels relative to plasma osmolality was significantly higher than that in normal subjects (12.6 +/- 4.9 pmol/L), although there was a considerable individual variation in plasma ANP ranging from normal to clearly elevated levels (15.1-47.0 pmol/L). When hyponatremia was corrected by water restriction or demeclocycline administration, plasma ANP levels decreased significantly and fell into the normal range (12.5 +/- 4.3 pmol/L). DI patients who complained of polyuria and polydipsia and had hypoosmolar urine, normal or elevated plasma sodium concentrations, and decreased plasma AVP levels relative to plasma osmolality, on the other hand, had a significantly lower mean plasma ANP level (7.6 +/- 2.9 pmol/L) than normal subjects. There was, again, a considerable overlap between plasma ANP levels in individual DI patients (4.2-13.9 pmol/L) and those in normal subjects. Treatment with 1-desamino-8-D-arginine vasopressin resulted in a significant increase in the mean plasma ANP level (18.6 +/- 8.0 pmol/L). There were no significant correlations between plasma ANP and AVP levels in either group of patients. The results indicate that ANP secretion is modulated by changes in plasma volume consequent to abnormal AVP secretion, which may have a pathophysiological significance in maintaining volume homeostasis.

Single-dose tetracycline labeling for bone histomorphometry.

A single oral dose of tetracycline deposits in bone and is readily identified with fluorescence microscopy. Two such time-spaced labels can be used to determine bone dynamic features. This is as accurate as conventional three-day labeling periods. The simplicity, improved compliance, and substantial reduction in time it takes to prepare a patient for bone biopsy all appear to be advantageous when compared with current recommendations.

The effect of an antibiotic/corticosteroid paste on inflammatory root resorption in vivo.

Progressive external inflammatory root resorption, a result of persistent inflammation within the periodontal membrane, will cause eventual destruction of the tooth root if the inflammation is not eradicated. This study examined the effects of an antibiotic/corticosteroid paste on experimental inflammatory resorption induced in monkeys in vivo. Histologic evaluation of results with the use of a morphometric technique revealed that the paste eliminated inflammatory root resorption and had no damaging effects upon the periodontal membrane. It was concluded that this antibiotic/corticosteroid combination is an effective medication for use in the treatment of progressive root resorption in traumatically injured teeth.

Demeclocycline-induced natriuresis and renal insufficiency: in vivo and in vitro studies.

We examined renal function and Na+ balance in a patient with congestive heart failure who was treated with demeclocycline (DMC) on three separate occasions under strict metabolic balance conditions. Natriuresis and reversible renal insufficiency, which could not be explained solely on the basis of negative Na+ balance, developed on each occasion. In contrast to reports of an association between elevated serum DMC levels and renal insufficiency in patients with cirrhotic edema, the renal insufficiency in this patient with cardiac edema occurred in the absence of high DMC levels. Consequently, markedly elevated serum DMC levels do not appear to be a prerequisite for the development of natriuresis or renal insufficiency in edematous patients receiving this drug. In an attempt to clarify the mechanism of the natriuresis, we also examined the effects of DMC on Na+ transport in an in-vitro model system, the toad urinary bladder. DMC inhibited aldosterone-stimulated Na+ transport, but had no effect on Na+ transport when the latter was jointly stimulated by ADH and theophylline. Despite this selective inhibition of the natriferic effect of aldosterone in vitro, it is unlikely that such a mechanism completely accounts for the natriuresis observed in-vivo since the natriuresis is generally of large magnitude and is usually accompanied by some degree of kaliuresis, and DMC had no consistent effect on urinary aldosterone excretion. Consequently, other mechanisms must be sought to explain the natriuretic effect of DMC in edematous patients. Likewise, mechanisms other than negative Na+ balance (perhaps primary alterations in renal hemodynamics) must underly the development of renal insufficiency in such individuals.

The effect of protracted tetracycline treatment on bone growth and maturation.

Mature female rhesus monkeys were used to evaluate the effects of a one-year course of tetracycline (50 mg/kg/day, intramuscularly) on the formation, maturation, and mineralization of mandibular bone. The bones from the treated group contained normal concentrations of calcium (Ca), inorganic phosphorus (Pi), and hydroxyproline (HO-Pr), and the treatment schedule did not alter the distribution (percentage) of total osteons into slightly, moderately, and highly mineralization classes. Tetracycline impairs bone mineralization and the subsequent maturation of the mineral and matrix moieties. The percentage of highly mineralized osteons labeled with tetracycline is subnormal. Density gradient fractionation studies indicate the presence of abnormally high Ca/Pi ratios in the temporally young newly formed bone mineral and somewhat higher ratios in the most mature bone fraction. Protracted tetracycline treatment at high dosages impairs bone growth and maturation in adult rhesus monkeys.

Effect of antacids on the dissolution of minocycline and demethylchlortetracycline from capsules.

The effect of certain antacids on the dissolution of minocycline and demethylchlortetracycline from capsules was studied. It was found that antacids such as aluminium silicate and magnesium trisilicate decreased the dissolution of minocycline and demethyl-chlortetracycline.

Double-blind comparison of two regimens in the treatment of nongonococcal urethritis. Seven-day vs 21-day course of triple tetracyclinc (Deteclo).

In a double-blind comparison of two regimens of triple tetracycline (Deteclo, Lederle) in the treatment of nongonococcal urethritis, 68 (88.6%) of 70 patients treated with one tablet twice for 21 days and seen four weeks after starting therapy had satisfactory results. This was significantly better than the findings among the 73 patients treated with one tablet twice daily for seven days and followed for four weeks, among whom only 47 (64.4%) had satisfactory results. Results were also better for the group treated with the 21-day regimen at three months afer the start of treatment. When analysed individually at four and 12 weeks, urethral discharge, urethral Gram-stained smears, and first-glass urine test all gave similar results, which were markedly better than those before treatment. It appears that the longer course of treatment it indicated where any regular partner may not be treated. Slightly fewer patients had satisfactory results among those who admitted consuming alcohol than among those who did not. Chlamydiae-negative patients, treated for seven days, had fewer clinically satisfactory results than other sub-groups.

[Treatment of inappropriate ADH secretion syndrome with demethylchlortetracycline]. / Traitement du syndrome de sécrétion inappropriée d'hormone antidiurétique par la déméthylchlortetracycline.

A sixteen month girl with inappropriate ADH secretion was treated with demethylchlortetracycline. On a dose of 20 mgs/kg/day the disorder resolved completely. Treatment was continued with a maintenance dose of 15 mgs/kg/day. No side effects were observed.