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Pharmaceuticals (Basel, Switzerland) Sep 2016An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired...
An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix(®) paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20-40 min at a concentration of 40-80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100-200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication.
PubMed: 27618065
DOI: 10.3390/ph9030056 -
Endocrinology, Diabetes & Metabolism... 2015The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case...
UNLABELLED
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case reports describing chronic SIADH and all resolved within 12 months, except for one case complicated by meningo-encephalitis. Persistent symptomatic hyponatremia due to chronic SIADH was present for 4 years following a TBI in a previously well 32-year-old man. Hyponatremia consistent with SIADH initially occurred in the immediate period following a high-speed motorbike accident in 2010. There were associated complications of post-traumatic amnesia and mild cognitive deficits. Normalization of serum sodium was achieved initially with fluid restriction. However, this was not sustained and he subsequently required a permanent 1.2 l restriction to maintain near normal sodium levels. Multiple episodes of acute symptomatic hyponatremia requiring hospitalization occurred over the following years when he repeatedly stopped the fluid restriction. Given the ongoing nature of his hyponatremia and difficulties complying with strict fluid restriction, demeclocycline was commenced in 2014. Normal sodium levels without fluid restriction have been maintained for 6 months since starting demeclocycline. This case illustrates an important long-term effect of TBI, the challenges of complying with permanent fluid restrictions and the potential role of demeclocycline in patients with chronic hyponatremia due to SIADH.
LEARNING POINTS
Hyponatraemia due to SIADH commonly occurs after TBI, but is usually mild and transient.Chronic hyponatraemia due to SIADH following TBI is a rare but important complication.It likely results from damage to the pituitary stalk or posterior pituitary causing inappropriate non-osmotic hypersecretion of ADH.First line management of SIADH is generally fluid restriction, but hypertonic saline may be required in severe cases. Adherence to long-term fluid restriction is challenging. Other options include oral urea, vasopressin receptor antagonists and demeclocycline.While effective, oral urea is poorly tolerated and vasopressin receptor antagonists are currently not licensed for use in Australia or the USA beyond 30 days due to insufficient long-term safety data and specific concerns of hepatotoxicity.Demeclocycline is an effective, well-tolerated and safe option for management of chronic hyponatraemia due to SIADH.
PubMed: 26527077
DOI: 10.1530/EDM-15-0070 -
International Journal of Clinical... Dec 2015Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic... (Review)
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.
Topics: Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome
PubMed: 26289137
DOI: 10.1111/ijcp.12713 -
European Journal of Clinical... Aug 2015Hyponatraemia is a very common medical condition that is associated with multiple poor clinical outcomes and is often managed suboptimally because of inadequate...
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.
Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Hospitalization; Humans; Hyponatremia; Inappropriate ADH Syndrome; Practice Guidelines as Topic; Tolvaptan; Water-Electrolyte Imbalance
PubMed: 25995119
DOI: 10.1111/eci.12465 -
Journal of Biomedical Optics Sep 2014Contrast agents have shown to be useful in the detection of cancers. The goal of this study was to compare enhancement of brain cancer contrast using reflectance and... (Comparative Study)
Comparative Study
Contrast agents have shown to be useful in the detection of cancers. The goal of this study was to compare enhancement of brain cancer contrast using reflectance and fluorescence confocal imaging of two fluorophores, methylene blue (MB) and demeclocycline (DMN). MB absorbs light in the red spectral range and fluoresces in the near-infrared. It is safe for in vivo staining of human skin and breast tissue. However, its safety for staining human brain is questionable. Thus, DMN, which absorbs light in the violet spectral range and fluoresces between 470 and 570 nm, could provide a safer alternative to MB. Fresh human gliomas, obtained from surgeries, were cut in half and stained with aqueous solutions of MB and DMN, respectively. Stained tissues were imaged using multimodal confocal microscopy. Resulting reflectance and fluorescence optical images were compared with hematoxylin and eosin histopathology, processed from each imaged tissue. Results indicate that images of tissues stained with either stain exhibit comparable contrast and resolution of morphological detail. Further studies are required to establish the safety and efficacy of these contrast agents for use in human brain.
Topics: Brain; Brain Chemistry; Brain Neoplasms; Contrast Media; Demeclocycline; Glioma; Humans; Image Processing, Computer-Assisted; Methylene Blue; Optical Imaging
PubMed: 25239672
DOI: 10.1117/1.JBO.19.9.090504 -
Journal of Cardiology Cases Nov 2014Hyponatremia commonly occurs in acute coronary syndrome and has been recognized as a worse prognostic indicator in patients with ST-segment elevation myocardial...
Hyponatremia commonly occurs in acute coronary syndrome and has been recognized as a worse prognostic indicator in patients with ST-segment elevation myocardial infarction (STEMI). However STEMI with preexisting hyponatremia from syndrome of inappropriate antidiuretic hormone secretion (SIADH) has never been described in the literature. We describe a case of 59-year-old woman who presented with STEMI and received emergent percutaneous coronary intervention who also had SIADH with the lowest serum sodium measurement of 113 mmol/L. Initially, she was treated with hypertonic saline to reduce central nervous system complications. Then, vasopressin receptor 2 antagonist and demeclocycline were started as well as fluid restriction and salt tablet. Her sodium level and clinical symptoms improved. Subsequently, we found cavitary right upper lung mass and a biopsy report revealed small cell lung cancer as a cause of SIADH. Severe hyponatremia from SIADH complicated with STEMI could potentially have reduced adverse outcomes by normalizing sodium level through vasopressin receptor 2 antagonist or demeclocycline. < Hyponatremia in STEMI from SIADH, prognosis, and treatment options.>.
PubMed: 30534240
DOI: 10.1016/j.jccase.2014.07.007 -
TheScientificWorldJournal 2014This study examined the extent to which intervisit corticosteroid-based antibiotic pastes (CAP) medicaments contribute to staining of tooth structure after attempted...
AIMS
This study examined the extent to which intervisit corticosteroid-based antibiotic pastes (CAP) medicaments contribute to staining of tooth structure after attempted removal by irrigation techniques.
METHODS
A total of 140 roots were prepared and the canals were filled with Ledermix paste (demeclocycline), Odontopaste (clindamycin), and Doxypaste (doxycycline). The pastes were removed after 2 or 4 weeks of storage in the dark using EDTA and NaOCl with either a 27-gauge-slotted needle or an EndoActivator (Dentsply). The roots were then exposed to an intense light source for 30 minutes each week and photographed after a further 1, 3, or 6 months. Digital images were standardized and data for changes in luminosity were analysed using repeated measures ANOVA and a post hoc test.
RESULTS
Removal of the medicament did not prevent later discolouration. There was no significant difference between the paste removal methods. Ledermix paste caused the greatest darkening compared to the untreated controls, for both application periods and both methods of removal. Doxypaste and Odontopaste caused less darkening than Ledermix.
CONCLUSION
Medicaments that stain teeth may continue to discolour teeth despite best attempts to remove them. This study stresses the importance of material selection and minimising contact of Ledermix within the coronal aspects of teeth.
Topics: Anti-Bacterial Agents; Color; Humans; In Vitro Techniques; Root Canal Irrigants; Tooth Discoloration; Tooth Root
PubMed: 24688386
DOI: 10.1155/2014/404676 -
American Journal of Physiology. Renal... Dec 2013Binding 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...
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.
Topics: Adenylyl Cyclases; Animals; Anti-Bacterial Agents; Aquaporin 2; Cells, Cultured; Cyclic AMP; Deamino Arginine Vasopressin; Demeclocycline; Disease Models, Animal; Hyponatremia; In Vitro Techniques; Inappropriate ADH Syndrome; Kidney Medulla; Male; Mice; Minocycline; Rats; Rats, Wistar; Vasopressins
PubMed: 24154696
DOI: 10.1152/ajprenal.00723.2012 -
Indian Journal of Pharmaceutical... Nov 2012A simple, rapid, specific and sensitive liquid chromatography tandem mass spectrometric method has been developed and validated for the determination of doxycycline from...
A simple, rapid, specific and sensitive liquid chromatography tandem mass spectrometric method has been developed and validated for the determination of doxycycline from the human plasma. Doxycycline is extracted from human plasma by solid phase extraction. Demeclocycline was used as an internal standard. Detection was performed at transitions of 444.800→428.200 for doxycycline and 464.700→448.100 for demeclocycline using mass spectrometry. Chromatographic separation of analyte and internal standard were carried out using a reverse phase C18, column at 0.500 ml/min flow. The assay of doxycycline is linear over the range of 0.055-7.612 μg/ml, with a precision <14.83%, regression coefficient (r(2))=0.9961 and the limit of quantification in plasma for doxycycline was 0.055 μg/ml. Mean extraction recovery obtained was 95.55%. Samples are stable at room temperature for 6 h, processed samples were stable at least for 30.20 h and also stable at three freeze-thaw cycles. The method has been used to perform pharmacokinetic and bioequivalence studies in human plasma.
PubMed: 23798780
DOI: 10.4103/0250-474X.110599 -
Case Reports in Nephrology and Urology Jan 2013Hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) during amiodarone therapy is a rare but potentially lethal adverse effect....
INTRODUCTION
Hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) during amiodarone therapy is a rare but potentially lethal adverse effect. We report a case of severe hyponatremia associated with amiodarone, and discuss its clinical implications.
CASE REPORT
An 84-year-old Caucasian man with a past medical history of hypertension and diabetes was admitted to the hospital with a non-ST elevation myocardial infarction. He underwent coronary artery bypass graft and developed atrial fibrillation on postoperative day 2. A loading dose of amiodarone followed by a maintenance dose was started. The serum sodium level was 136 mmol/l at discharge and subsequently decreased to 105 mmol/l 11 days later, at which time the patient represented with altered mental status. The diagnosis of SIADH was made based on euvolemic hypoosmotic hyponatremia, lack of any other medication known to cause SIADH and urine that was less than maximally dilute. The serum sodium increased gradually to 123 mmol/l after 36 h of treatment with hypertonic saline, demeclocycline and fluid restriction.
CONCLUSION
SIADH-induced hyponatremia associated with amiodarone occurs rarely. Since severe hyponatremia is associated with significant neurological damage and mortality, clinicians should carefully monitor serum sodium during amiodarone therapy.
PubMed: 23687510
DOI: 10.1159/000350910