Interventions for treating traumatised permanent front teeth: avulsed (knocked out) and replanted.

BACKGROUND: Traumatic dental injuries are common. One of the most severe injuries is when a permanent tooth is knocked completely out of the mouth (avulsed). In most circumstances the tooth should be replanted as quickly as possible. There is uncertainty on which interventions will maximise the survival and repair of the replanted tooth. This is an update of a Cochrane Review first published in 2010. OBJECTIVES: To compare the effects of a range of interventions for managing traumatised permanent front teeth with avulsion injuries. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 March 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2) in the Cochrane Library (searched 8 March 2018), MEDLINE Ovid (1946 to 8 March 2018), and Embase Ovid (1980 to 8 March 2018). The US National Institutes of Health Ongoing Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We considered randomised and quasi-randomised controlled trials that included a minimum follow-up period of 12 months, for interventions for avulsed and replanted permanent front teeth. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias. Authors were contacted where further information about their study was required. MAIN RESULTS: Four studies, involving a total of 183 participants and 257 teeth were identified. Each of the interventions aimed to reduce infection or alter the inflammatory response or both at the time of or shortly after the tooth or teeth were replanted. Each study assessed a different intervention and therefore it was not appropriate or possible to numerically synthesise the data. All evidence was rated as being of very low quality due to problems with risk of bias and imprecision of results. This means that we are very uncertain about all of the results presented in this review.One study at high risk of bias with 69 participants (138 teeth) compared a 20-minute soak with gentamycin sulphate for both groups prior to replantation with the experimental group receiving daily hyperbaric oxygen for 80 minutes for the first 10 days. There was some evidence of a benefit for the hyperbaric oxygen group in respect of periodontal healing, tooth survival, and pulpal healing.One study at unclear risk of bias with 22 participants (27 teeth) compared the use of two root canal medicaments, Ledermix and Ultracal. There was insufficient evidence of a difference for periodontal healing or tooth survival. This was the only study to formally report adverse events with none identified. Study authors reported that Ledermix caused a greater level of patient dissatisfaction with the colour of avulsed and replanted teeth.A third study at high risk of bias with 19 participants compared extra- or intra-oral endodontics for avulsed teeth which were stored dry for longer than 60 minutes before replantation. There was insufficient evidence of a difference in periodontal healing.The fourth study at high risk of bias with 73 participants compared a 10-minute soak in either thymosin alpha 1 or saline before replantation followed by daily gingival injections with these same medicaments for the first 7 days. There was some evidence of a benefit for thymosin alpha 1 with respect to periodontal healing and tooth survival. AUTHORS' CONCLUSIONS: Based on the results of the included studies, there is insufficient evidence to support or refute the effectiveness of different interventions for avulsed and replanted permanent front teeth. The overall quality of existing evidence was very low, and therefore great caution should be exercised when generalising the results of the included trials. There is urgent need for further well-designed randomised controlled trials.

TAR cloning and integrated overexpression of 6-demethylchlortetracycline biosynthetic gene cluster in Streptomyces aureofaciens.

6-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of tigecycline, minocycline, and amadacyclin (PTK 0796). In this study, the 6-DCT biosynthetic gene cluster (BGC) was cloned from genomic DNA of a high 6-DCT-producing strain, S. aureofaciens DM-1, using the transformation-associated recombination method. An extra copy of the 6-DCT BGC was introduced and integrated into the chromosome of S. aureofaciens DM-1. Duplication of the 6-DCT BGC resulted in a maximum increase of the 6-DCT titer by 34%.

Influence of the bleaching interval on the luminosity of long-term discolored enamel-dentin discs.

OBJECTIVES: The aim of this study is to investigate the influence of changing the sodium perborate-tetrahydrate (PBS-4) at a 4-day interval versus no change after 16 days of internal bleaching. MATERIALS AND METHODS: Two hundred and ten bovine enamel-dentin discs were discolored for 3.5 years with 14 different endodontic materials. All groups with a discoloring index of ∆E (mean) ≥ 5.5 were included in the present investigation: ApexCal (APCA), MTA white + blood (WMTA+BL), Portland cement + blood (PC+BL), blood (BL), MTA gray (GMTA), MTA gray + blood (GMTA+BL), Ledermix (LED), and triple antibiotic paste containing minocycline (3Mix). Fourteen specimens of each group were randomly assigned into two treatment groups: (1) no change of the PBS-4 (n = 7); (2) change of the PBS-4 every 4 days (n = 7). Color measurements were taken at 10 different time intervals and the L*a*b* values were recorded with a spectrophotometer (VITA Easyshade® compact). RESULTS: In the group 3Mix, significantly better results were achieved by changing the bleaching agent every 4 days (P = 0.0049; q = 0.04), while the group WMTA+BL indicated better results by no change of the bleaching agent (P = 0.0222, q = 0.09). All remaining groups showed no statistical difference between the two treatment procedures. CONCLUSIONS: Moderate discolorations can be successfully treated without changing the bleaching agent over a period of 16 days. Changing the sodium perborate-tetrahydrate every 4 days is preferred in case of severe discolored enamel-dentin discs only. CLINICAL RELEVANCE: This approach may offer a reduced number of clinical appointments and a secondary cost reduction to the patient.

The diagnosis and management of inpatient hyponatraemia and SIADH.

BACKGROUND: Hyponatraemia is a very common medical condition that is associated with multiple poor clinical outcomes and is often managed suboptimally because of inadequate assessment and investigation. Previously published guidelines for its management are often complex and impractical to follow in a hospital environment, where patients may present to divergent specialists, as well as to generalists. DESIGN: A group of senior, experienced UK clinicians, met to develop a practical algorithm for the assessment and management of hyponatraemia in a hospital setting. The latest evidence was discussed and reviewed in the light of current clinical practicalities to ensure an up-to-date perspective. An algorithm was largely developed following consensus opinion, followed up with subsequent additions and amendments that were agreed by all authors during several rounds of review. RESULTS: We present a practical algorithm which includes a breakdown of the best methods to evaluate volume status, simple assessments for the diagnosis of the various causes and a straightforward approach to treatment to minimise complexity and maximise patient safety. CONCLUSION: The algorithm we have developed reflects the best available evidence and extensive clinical experience and provides practical, useable guidance to improve patient care.

Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review.

AIMS: Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). The precise mechanism of action of demeclocycline is unclear, but has been linked to the induction of nephrogenic diabetes insipidus. Furthermore, the safety profile of demeclocycline is variable with an inconsistent time to onset, and a potential for complications. There has been no systematic evaluation of the use of demeclocycline for the treatment of HN secondary to SIADH to date. A systematic literature review was performed to obtain an insight into the clinical safety and efficacy of demeclocycline for this condition. METHODS: Embase(™) , MEDLINE(®) , MEDLINE(®) In-Process, and The Cochrane Library were searched on two occasions using MeSH terms combined with free-text terms. References were screened by two independent reviewers. Relevant publications were then extracted by two independent reviewers, with a third reviewer collating and finalising extractions. RESULTS: The searches returned a total of 705 hits. 632 abstracts were screened after the removal of duplicates. Following screening, 35 full-length publications were reviewed. Of these, 17 were excluded, resulting in 18 studies deemed relevant for data extraction. Two were randomised controlled trials (RCTs), 16 were non-RCTs, and 10 were case reports. DISCUSSION: Although most reports suggest that demeclocycline can address serum sodium levels in specific patients with HN, efficacy is variable, and may depend upon the underlying aetiology. Demeclocycline dose adjustments can be complex, and as its use in clinical practice is not well defined, it can differ between healthcare professionals. CONCLUSION: There is a lack of clinical and economic evidence supporting the use of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline for HN secondary to SIADH must be closely monitored.

Management of euvolemic hyponatremia attributed to SIADH in the hospital setting.

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients. Acute and severe hyponatremia can be a life-threatening condition, but recent evidence indicates that also mild and chronic hyponatremia is associated with neurological and extra-neurological signs, such as gait disturbances, attention deficits, falls and fracture occurrence, and bone loss. The syndrome of inappropriate ADH secretion (SIADH) is the most frequent cause of hyponatremia. Hyponatremia secondary to SIADH may result for instance from ectopic release of ADH in lung cancer, from diseases affecting the central nervous system, from pneumonia or other pneumopathies or as a side-effect of various drugs In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external sodium balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest oedema are usually seen. Neurological impairment may range from subclinical to life-threatening, depending on the degree and mostly on the rate of serum sodium reduction. The management of hyponatremia secondary to SIADH is largely dependent on the symptomatology of the patient. This review briefly summarizes the main aspects related to hyponatremia and then discusses the available treatment options for the management of SIADH, including vaptans, which are vasopressin receptor antagonists targeted for the correction of euvolemic hyponatremia, such as that observed in SIADH.

Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla.

Binding of vasopressin to its type 2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin (AQP)2 water channels to the plasma membrane, and water reabsorption from the prourine. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline's mechanism of action, which is poorly understood, is studied here. In mouse cortical collecting duct (mpkCCD) cells, which exhibit deamino-8-D-arginine vasopressin (dDAVP)-dependent expression of endogenous AQP2, demeclocycline decreased AQP2 abundance and gene transcription but not its protein stability. Demeclocycline did not affect vasopressin type 2 receptor localization but decreased dDAVP-induced cAMP generation and the abundance of adenylate cyclase 3 and 5/6. The addition of exogenous cAMP partially corrected the demeclocycline effect. As in patients, demeclocycline increased urine volume, decreased urine osmolality, and reverted hyponatremia in an SIADH rat model. AQP2 and adenylate cyclase 5/6 abundances were reduced in the inner medulla but increased in the cortex and outer medulla, in the absence of any sign of toxicity. In conclusion, our in vitro and in vivo data indicate that demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments.

The effect of calcium hydroxide on the antibiotic component of Odontopaste and Ledermix paste.

AIM: To investigate the chemical interaction of calcium hydroxide with the antibiotics demeclocycline calcium in Ledermix Paste and clindamycin hydrochloride in Odontopaste. METHODOLOGY: Validated methods were developed to analyse the interaction of calcium hydroxide in two forms, Pulpdent and calcium hydroxide powder, with the two antibiotics. High-performance liquid chromatography (HPLC) was used to analyse the mixed samples of the pastes and calcium hydroxide. The concentration of demeclocycline calcium over 0-, 1-, 18-, 24-, 72-h and 7-day time-points was determined. The concentration of clindamycin hydrochloride over 1-, 6-, 24-, 72-h and 7-day time-points was determined. All tests with HPLC involved testing of the standard in duplicate alongside the samples. Linearity, precision and specificity of the testing procedures and apparatus were validated. Descriptive statistics are provided. RESULTS: The antibiotics in both Odontopaste and Ledermix Paste were affected by the addition of calcium hydroxide. When mixed with calcium hydroxide powder, Odontopaste had a 2% loss of clindamycin hydrochloride over 7 days, but when mixed with Pulpdent, there was a 36% loss over 7 days. Ledermix Paste showed an 80% loss of demeclocycline calcium over 7 days when mixed with calcium hydroxide powder and a 19% loss when mixed with Pulpdent over the 7-day period. CONCLUSION: The addition of calcium hydroxide to Odontopaste or Ledermix Paste results in reductions of the respective antibiotic over a 7-day time period.

The diagnosis and conservative treatment of a complex type 3 dens invaginatus using cone beam computed tomography (CBCT) and 3D plastic models.

AIM: To investigate the use of 3D plastic models, printed from cone beam computed tomography (CBCT) data, for accurate diagnosis and conservative treatment of a complex case of dens invaginatus. SUMMARY: A chronic apical abscess with a draining sinus tract was diagnosed during the treatment planning stage of orthodontic therapy. Radiographic examination revealed a large radiolucent area associated with an invaginated right maxillary central incisor, which was found to contain a vital pulp. The affected tooth was strategic in the dental arch. Conventional periapical radiographs provided only partial information about the invagination and its relationship with the main root canal and with the periapical tissues. A limited-volume CBCT scan of the maxilla did not show evidence of communication between the infected invagination and the pulp in the main root canal, which could explain the pulp vitality. A novel method was adopted to allow for instrumentation, disinfection and filling of the invagination, without compromising the vitality of the pulp in the complex root canal system. The CBCT data were used to produce precise 3D plastic models of the tooth. These models facilitated the treatment planning process and the trial of treatment approaches. This approach allowed the vitality of the pulp to be maintained in the complex root canal space of the main root canal whilst enabling the healing of the periapical tissues. KEY LEARNING POINTS: Even when extensive periapical pathosis is associated with a tooth with type III dens invaginatus, pulp sensibility tests should be performed. CBCT is a diagnostic tool that may allow for the management of such teeth with complex anatomy. 3D printed plastic models may be a valuable aid in the process of assessing and planning effective treatment modalities and practicing them ex vivo before actually performing the clinical procedure. Unconventional technological approaches may be required for detailed treatment planning of complex cases of dens invaginatus.

A randomized phase 2 study on demeclocycline in patients with mild-to-moderate COVID-19.

Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of demeclocycline in patients hospitalized with mild-to-moderate COVID-19 via an open-label, multicenter, parallel-group, randomized controlled phase 2 trial. Primary and secondary outcomes included changes from baseline (day 1, before the study treatment) in lymphocytes, cytokines, and SARS-CoV-2 RNA on day 8. Seven, seven, and six patients in the control, demeclocycline 150 mg daily, and demeclocycline 300 mg daily groups, respectively, were included in the modified intention-to-treat population that was followed until day 29. A significant change of 191.3/µL in the number of CD4+ T cells from day 1 to day 8 was observed in the demeclocycline 150 mg group (95% CI 5.1/µL-377.6/µL) (p = 0.023), whereas that in the control group was 47.8/µL (95% CI - 151.2/µL to 246.8/µL), which was not significant (p = 0.271). The change rates of CD4+ T cells negatively correlated with those of IL-6 in the demeclocycline-treated groups (R = - 0.807, p = 0.009). All treatment-emergent adverse events were of mild-to-moderate severity. The present results indicate that the treatment of mild-to-moderate COVID-19 patients with demeclocycline elicits immune responses conducive to recovery from COVID-19 with good tolerability.Trial registration: This study was registered with the Japan Registry of Clinical Trials (Trial registration number: jRCTs051200049; Date of the first registration: 26/08/2020).

Development and validation of a reversed-phase liquid chromatographic method for analysis of demeclocycline and related impurities.

A simple, robust, and rapid reversedphase high-performance liquid chromatographic method for the analysis of demeclocycline and its impurities is described. Chromatographic separations were achieved on a Symmetry Shield RP8 (75 mm × 4.6 mm, 3.5 µm) column kept at 40°C. The mobile phase was a gradient mixture of acetonitrile, 0.06 M sodium edetate (pH 7.5), 0.06 M tetrapropylammonium hydrogen sulphate (pH 7.5) and water, A (2:35:35:28 v/v/v/v) and B (30:35:35:0 v/v/v/v) pumped at a flow rate of 1 mL/min. UV detection was performed at 280 nm. The developed method was validated according to the ICH guidelines for specificity, limit of detection, limit of quantification, linearity, precision, and robustness. An experimental design was applied for robustness study. Results show that the peak shape, chromatographic resolution between the impurities, and the total analysis time are satisfactory and better than previous methods. The method has been applied for the analysis of commercial demeclocycline bulk samples available on the market.

Tooth discoloration induced by endodontic materials: a laboratory study.

AIM: To investigate the discoloration potential of endodontic materials using a bovine tooth model. METHODOLOGY: Two hundred and 10 dentine-enamel cuboid blocks (10 × 10 × 3.5 mm) were prepared out of the middle thirds of bovine tooth crowns. Standardized cavities were prepared in the walls of the pulp chamber leaving 2 mm of enamel and dentine on the labial wall of the crown. The specimens were randomly assigned to 14 groups (n = 15). Endodontic materials were placed into the cavities as follows: group A: empty, group B: blood, group C: calcium hydroxide, group D: ApexCal, group E: Ultracal XS, group F: Ledermix, group G: triple antibiotic paste (3Mix), group H: grey MTA(GMTA), group I: GMTA + blood, group J: white MTA (WMTA), group K: WMTA + blood, group L: Portland cement (PC), group M: PC + blood and group N: AH Plus. The cavities were sealed with composite and stored in water. Standardized colour measurement (VITA Easyshade compact) was performed at the following intervals: prior to (T0) and after placement of the filling (T1), 1 week (T2), 1 month (T3), 3 months (T4), 6 months (T5) and after 1 year (T6). Colour change (ΔE) values were calculated. A two-way analysis of variance was used to assess significant differences between the endodontic materials. The mean values of all groups were compared using the Tukey multiple comparison test (α = 0.05). RESULTS: Significant differences were detected amongst the experimental groups after 12 months (P < 0.0001). The lowest colour change values were observed in the groups N (AH Plus, 3.2 ± 1.5), A (empty, 3.8 ± 1.4), L (PC, 4.1 ± 1.7), C (calcium hydroxide, 4.7 ± 1.5), E (Ultracal XS, 5.1 ± 1.9) and J (WMTA, 7.9 ± 6.7). The most discoloration was measured in groups G (3Mix, 66.2 ± 9.9) and F (Ledermix, 46.2 ± 11.6). PC showed the best colour stability amongst the Portland cement-based materials; however, when contaminated with blood (group M), a significantly higher ΔE value (13.6 ± 4.2) was detected (P = 0.032). CONCLUSION: Materials used in endodontics may stain teeth. Therefore, the choice of material should not rely solely on biological and functional criteria, but also take aesthetic considerations into account.

Intracanal dressing and root canal filling materials in tooth replantation: a literature review.

The prognosis of tooth replantation is usually related to the need of endodontic treatment, which has a direct relationship with the occurrence of root resorptions. Several studies have been undertaken in an attempt to prevent, delay, or treat these complications, which are the main causes of loss of replanted teeth. This literature review examines research evidence on intracanal dressings and root canal filling materials used in cases of tooth replantation. A comprehensive search was performed in the Medline/Pubmed, Bireme and Scielo full-text electronic journal databases to retrieve English-language articles referring to these topics that had been published between 1964 and 2010. Calcium hydroxide (CH) remains the usually recommended choice as an intracanal medicament in replanted teeth; however, there is evidence to support the initial use of a corticosteroid-antibiotic combination such as Ledermix paste to control potential early resorption, prior to the introduction of CH where the beneficial effect in the treatment of progressive root resorption has been well proven. Regarding root filling materials, CH-containing sealers are a good option because of their biological properties. Accurate diagnosis and adequate treatment plan may constitute very complex tasks, particularly in tooth avulsion because several variables are involved. In addition to the technical knowledge and clinical experience directed toward the quality of treatment, patient education may favorably influence the survival of replanted teeth.

Periodontal healing following avulsion and replantation of teeth: a multi-centre randomized controlled trial to compare two root canal medicaments.

BACKGROUND: Non-setting calcium hydroxide (Ultracal XS(®) ) is recommended by the International Association of Dental Traumatology as the initial medicament following avulsion and replantation for mature teeth. There is experimental evidence to suggest Ledermix(®) , placed as an alternative inter-visit dressing may improve periodontal healing. AIM: This study investigated, using a multi-centre randomized controlled trial, the effect of two root canal medicaments, Ledermix(®) and Ultracal XS(®) , on periodontal healing of avulsed and replanted teeth. MATERIAL AND METHODS: Children were recruited if they fulfilled all inclusion criteria. Treatment followed a standardized protocol. Assessment of periodontal healing or ankylosis was made clinically and radiographically by an experienced, 'blinded', clinician at 12months. RESULTS: Over 200 patients were assessed for eligibility at five centres. Twenty-nine patients were eligible for inclusion. Final analysis involved 22 patients with 27 teeth. Ankylosis was detected in four of the 12 teeth in the Ledermix(®) group and nine of 15 in the Ultracal XS(®) group. No significant difference between medicaments was found in the proportion of teeth or patients showing periodontal healing. DISCUSSION: There was no significant difference in periodontal healing between the two medicaments at either a tooth or patient level. The numbers recruited fell short of an estimated power calculation. For patients meeting the inclusion criteria and completing the trial, periodontal healing was seen in 52% of teeth at the 12-month assessment between both groups. The only factor found to significantly influence the periodontal outcome was dry time.

Endodontic 'solutions' part 1: a literature review on the use of endodontic lubricants, irrigants and medicaments.

Endodontic lubricants, irrigants and medicaments help prepare and disinfect root canal systems (RCS) but primary and secondary cases involve different microbes and therefore it is unlikely that one protocol will be effective for both case types. Each individual 'solution' or sequence of'solutions' could play a significant role in each case type, but there are no detailed published guidelines in existence. To help inform clinical practice it was decided to undertake a literature review followed by a UK and Republic of Ireland wide audit on current endodontic'solution' usage within dental schools. The literature review was undertaken under the following headings: pre-op oral rinse; file lubricants; root canal irrigants and intracanal medicaments and provides an evidence base for protocol development for both primary and retreatment cases.The audit project and the protocols developed from the findings of both the literature review and audit will be presented in Part 2.

Development and Reversal of Discolouration in Roots Filled with Ledermix or Doxymix Pastes Stored in the Dark for Three Months then Daylight for Twenty Four Months.

OBJECTIVE: To explore the long-term effects on discolouration by demeclocycline HCl (Ledermix, LED) or doxycycline hyclate (Doxymix, DOX) pastes placed in extracted human teeth over a 27-month period under different storage conditions. METHODS: The canals in 38 teeth were prepared carefully, to minimize exposure to contamination from irrigants, then either LED (Lederle Pharmaceuticals, Germany) or DOX (Ozdent, Australia) were placed. Samples were stored in the dark for 3 months followed by daylight for 24 months. The storage conditions varied as follows: Group 1: Open access, dry storage (OD); Group 2: Closed access, dry storage (CD); Group 3: Open access, wet storage (OW); Group 4: Closed access, wet storage (n=4 for each material). Additional teeth were used as controls: Polyethylene glycol only in a closed canal; and saline only irrigation with LED paste in a closed canal. Standardised digital photographs were taken over 27 months and evaluated for changes in luminosity. RESULTS: Darkening of tooth structure occurred in all LED groups and in the two DOX groups that were stored wet, during exposure to light, with a faster rate with LED. The most rapid staining occurred with LED in moist conditions with an open access cavity. The least staining occurred with DOX in samples stored dry. With prolonged exposure to light, a reversal in staining occurred with DOX at 3 months and LED at 9 months. CONCLUSION: Staining of tooth structure is influenced by the choice of medicament, and by exposure to moisture and air. Light has a bimodal effect, first driving staining, but later reversing it. This can be explained by different wavelengths of light causing photodegradation and photo-oxidation of tetracyclines and their complexes with tooth mineral.

Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects. The molecule was obtained by removal the dimethylamino substituent at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF) in biophysical assays and in a SH-SY5Y-α-Syn-tRFP cell model. In addition, DDMC rendered α-SynPFF less inflammogenic. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in Parkinson's disease and other synucleinopathies.

The effect of calcium hydroxide on the steroid component of Ledermix and Odontopaste.

AIM: To investigate the chemical interaction of calcium hydroxide with the corticosteroid triamcinolone acetonide in Ledermix Paste and in Odontopaste, a new steroid/antibiotic paste. METHODOLOGY: Validated methods were developed to analyse the interaction of calcium hydroxide in two forms, Pulpdent Paste and calcium hydroxide powder, with triamcinolone acetonide within Odontopaste and Ledermix Paste. High-performance liquid chromatography (HPLC) was used to analyse the mixed samples of the pastes and calcium hydroxide. The concentration of triamcinolone acetonide within the pastes was determined over 0, 2, 6, 24 and 72-h time-points. All tests with the HPLC involved the testing of the standard with triplicate injections alongside the samples. All samples were tested in duplicate with each injected twice; therefore, four tests were performed for each investigation. Linearity, precision and specificity of the testing procedures and apparatus were validated. Descriptive statistics are provided. RESULTS: In both pastes, there was a marked rapid destruction of the triamcinolone acetonide steroid upon mixing with calcium hydroxide. Odontopaste suffered a lower rate of destruction of the triamcinolone acetonide component than Ledermix Paste, but both pastes showed very similar degrees of steroid destruction after 72 h. When using calcium hydroxide powder with Ledermix Paste, the triamcinolone was destroyed entirely and immediately. CONCLUSION: The addition of calcium hydroxide to Odontopaste or Ledermix Paste results in the rapid destruction of the steroid.

Comparison of ultrasonic irrigation and RinsEndo for the removal of calcium hydroxide and Ledermix paste from root canals.

AIM: To compare the efficacy of ultrasonic irrigation and RinsEndo in removing calcium hydroxide and Ledermix paste from simulated root canal irregularities. METHODOLOGY: The root canals of sixty extracted single-rooted teeth were prepared using FlexMaster rotary instruments to size 60, 0.02 taper. The roots were split longitudinally, and a standardized groove was prepared in the apical part of one segment. The teeth were randomly allocated into two groups (n = 30), according to the intracanal dressing. In the first group, grooves were filled with calcium hydroxide paste (Calxyl), whereas the grooves in the second group were filled with Ledermix paste. After reassembly, the root canals were completely filled with the respective medicament using a lentulo. The removal of medicament dressing was performed after 7 days with either passive ultrasonic irrigation or RinsEndo and 1% sodium hypochlorite for 3 min. The amount of remaining medicament was evaluated under a microscope with 30 × magnification using a four-grade scoring system. A regression analysis with P ≤ 0.05 was performed. RESULTS: Ledermix paste removal was significantly more effective than the removal of calcium hydroxide (P < 0.0001), whereas irrigation technique was not a significant factor (P = 0.3712). The percentages of complete removal of calcium hydroxide and Ledermix paste were 11.7% and 51.7%, respectively. CONCLUSIONS: None of the irrigation techniques was able to completely remove the intracanal medicaments from the apical part of the root canal. Irrespective of the irrigation technique, significantly less Ledermix paste was detected compared with calcium hydroxide.

Electrooxidation of tetracycline antibiotic demeclocycline at unmodified boron-doped diamond electrode and its enhancement determination in surfactant-containing media.

In this paper, for the first time, the study of voltammetric determination of tetracycline antibiotic demeclocycline was conducted. The oxidation of compound was investigated using a commercially available boron-doped diamond electrode pretreated electrochemically (anodic and subsequent cathodic). Addition of anionic surfactant, sodium dodecylsulfate (SDS) and cationic surfactant, cetyltrimethylammonium bromide (CTAB) to the demeclocycline-containing electrolyte solution at pH 2.0 and 9.0, respectively, was found to improve the sensitivity of the stripping voltammetric measurements. Employing square-wave stripping mode (after 30 s accumulation at open-circuit condition) in Britton-Robinson buffer, the limits of detection were found to be 1.17 µg mL-1 (2.3 × 10-6 M) for 4 × 10-4 SDS-containing buffer solution at pH 2, and 0.24 µg mL-1 (4.8 × 10-7 M) for 1 × 10-4 CTAB-containing buffer solution at pH 9.0. The feasibility of the developed approach for the quantification of demeclocycline was tested in urine samples.