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Endocrinology Feb 2013Transgenic overexpression of the Notch1 intracellular domain inhibits osteoblast differentiation and causes osteopenia, and inactivation of Notch1 and Notch2 increases...
Transgenic overexpression of the Notch1 intracellular domain inhibits osteoblast differentiation and causes osteopenia, and inactivation of Notch1 and Notch2 increases bone volume transiently and induces osteoblastic differentiation. However, the biology of Notch is cell-context-dependent, and consequences of Notch activation in cells of the osteoblastic lineage at various stages of differentiation and in osteocytes have not been defined. For this purpose, Rosa(Notch) mice, where a loxP-flanked STOP cassette placed between the Rosa26 promoter and the NICD coding sequence, were crossed with transgenics expressing the Cre recombinase under the control of the Osterix (Osx), Osteocalcin (Oc), Collagen 1a1 (Col2.3), or Dentin matrix protein1 (Dmp1) promoters. At 1 month, Osx-Cre;Rosa(Notch) and Oc-Cre;Rosa(Notch) mice exhibited osteopenia due to impaired bone formation. In contrast, Col2.3-Cre;Rosa(Notch) and Dmp1-Cre;Rosa(Notch) exhibited increased femoral trabecular bone volume due to a decrease in osteoclast number and eroded surface. In the four lines studied, cortical bone was either not present, was porous, or had the appearance of trabecular bone. Oc-Cre;Rosa(Notch) and Col2.3-Cre;Rosa(Notch) mice exhibited early lethality so that their adult phenotype was not established. At 3 months, Osx-Cre;Rosa(Notch) and Dmp1-Cre;Rosa(Notch) mice displayed increased bone volume, and increased osteoblasts although calcein-demeclocycline labels were diffuse and fragmented, indicating abnormal bone formation. In conclusion, Notch effects in the skeleton are cell-context-dependent. When expressed in immature osteoblasts, Notch arrests their differentiation, causing osteopenia, and when expressed in osteocytes, it causes an initial suppression of bone resorption and increased bone volume, a phenotype that evolves as the mice mature.
Topics: Animals; Bone Development; Bone Diseases, Metabolic; Bone and Bones; Cell Differentiation; Cell Lineage; Collagen Type II; Female; Femur; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Osteoblasts; Osteocalcin; Osteogenesis; Phenotype; Receptors, Notch; Sp7 Transcription Factor; Transcription Factors
PubMed: 23275471
DOI: 10.1210/en.2012-1732 -
Journal of Bone and Mineral Research :... Jan 2013
Topics: Bone and Bones; Demeclocycline; Humans; Osteogenesis; Staining and Labeling; Teriparatide; Tetracycline
PubMed: 23255455
DOI: 10.1002/jbmr.1818 -
International Endodontic Journal Jun 2013To investigate the chemical interaction of calcium hydroxide with the antibiotics demeclocycline calcium in Ledermix Paste and clindamycin hydrochloride in Odontopaste.
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.
Topics: Anti-Bacterial Agents; Calcium Hydroxide; Chromatography, High Pressure Liquid; Clindamycin; Demeclocycline; Drug Combinations; Drug Interactions; Humans; Hydrogen-Ion Concentration; Materials Testing; Powders; Root Canal Irrigants; Time Factors; Triamcinolone Acetonide
PubMed: 23186004
DOI: 10.1111/iej.12021 -
Therapeutic Advances in Endocrinology... Apr 2012Hyponatremia is the most frequent electrolyte disorder and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately one-third of...
Hyponatremia is the most frequent electrolyte disorder and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately one-third of all cases. In the diagnosis of SIADH it is important to ascertain the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements. SIADH should be treated to cure symptoms. While this is undisputed in the presence of grave or advanced symptoms, the clinical role and the indications for treatment in the presence of mild to moderate symptoms are currently unclear. Therapeutic modalities include nonspecific measures and means (fluid restriction, hypertonic saline, urea, demeclocycline), with fluid restriction and hypertonic saline commonly used. Recently vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH. Although clinical experience with vaptans is limited at this time, they appear advantageous to patients because there is no need for fluid restriction and the correction of hyponatremia can be achieved comfortably and within a short time. Vaptans also appear to be beneficial for physicians and staff because of their efficiency and reliability. The side effects are thirst, polydipsia and frequency of urination. In any therapy of chronic SIADH it is important to limit the daily increase of serum sodium to less than 8-10 mmol/liter because higher correction rates have been associated with osmotic demyelination. In the case of vaptan treatment, the first 24 h are critical for prevention of an overly rapid correction of hyponatremia and the serum sodium should be measured after 0, 6, 24 and 48 h of treatment. Discontinuation of any vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse. It may be necessary to taper the vaptan dose or restrict fluid intake or both.
PubMed: 23148195
DOI: 10.1177/2042018812437561 -
Journal of Separation Science Jun 2012A simple, robust, and rapid reversedphase high-performance liquid chromatographic method for the analysis of demeclocycline and its impurities is described....
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.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Demeclocycline; Drug Contamination
PubMed: 22733511
DOI: 10.1002/jssc.201101071 -
Head & Face Medicine Mar 2012The aim of this clinical trial was to compare the degree of short term post-operative irritation after application of a triamcinolone/demeclocycyline based or a calcium... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
The aim of this clinical trial was to compare the degree of short term post-operative irritation after application of a triamcinolone/demeclocycyline based or a calcium hydroxide based provisional cement.
METHODS
A total of 109 patients (55 female and 54 male; mean age: 51 ± 14 years) with primary or secondary dentinal caries were randomly assigned to the two treatment groups of this biomedical clinical trial (phase III). Selection criteria were good systemic health and treated teeth, which were vital and showed no symptoms of pulpitis. Up to three teeth were prepared for indirect metallic restorations, and the provisional restorations were cemented with a triamcinolone/demeclocycyline (Ledermix) or a calcium hydroxide (Provicol) based material. The intensity of post-operative pain experienced was documented according to the VAS (4, 12, 20, 24, and 82 h) and compared to VAS baseline.
RESULTS
A total of 159 teeth were treated (Ledermix: 83 teeth, Provicol: 76 teeth). The minor irritation of the teeth, experienced prior to treatment, was similar in both groups; however, 4 h after treatment this value was significantly higher in the Provicol group than in the Ledermix group (p < 0.005, t-test). After 12 h, the difference was no longer significant. The number of patients taking analgesics for post-treatment pain was higher in the Provicol group (n = 11/53) than in the Ledermix group (n = 3/56).
CONCLUSIONS
The patients had no long term post-operative pain experience in both groups. However, within the first hours after cementation the sensation of pain was considerably higher in the Provicol group than in the Ledermix group.
Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bone Cements; Calcium Hydroxide; Demeclocycline; Dental Caries; Drug Combinations; Female; Humans; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Prospective Studies; Triamcinolone Acetonide
PubMed: 22414157
DOI: 10.1186/1746-160X-8-9 -
International Endodontic Journal Dec 2011To investigate the chemical interaction of calcium hydroxide with the corticosteroid triamcinolone acetonide in Ledermix Paste and in Odontopaste, a new...
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.
Topics: Alkalies; Anti-Bacterial Agents; Calcium Hydroxide; Chromatography, High Pressure Liquid; Clindamycin; Demeclocycline; Drug Combinations; Drug Interactions; Humans; Hydrogen-Ion Concentration; Materials Testing; Powders; Root Canal Irrigants; Time Factors; Triamcinolone Acetonide
PubMed: 21902701
DOI: 10.1111/j.1365-2591.2011.01940.x -
Turk Psikiyatri Dergisi = Turkish... 2011Psychogenic polydipsia with associated hyponatremia is a potentially fatal condition observed in patients with chronic psychiatric illness, especially schizophrenia....
Psychogenic polydipsia with associated hyponatremia is a potentially fatal condition observed in patients with chronic psychiatric illness, especially schizophrenia. Recognition and management of this condition are difficult, as patients are uncooperative and secretive about their water intake, but are important in terms of the associated complications. Different strategies, including involuntary fluid restriction and use of various pharmacological agents, such as demeclocycline, propranolol, captopril, and naloxone, have been used for the treatment of this condition with inconsistent results. Antipsychotics have also been used in the treatment of polydipsia; however, their role is not clear as there are reports of antipsychotics both improving and causing polydipsia. Typical antipsychotics have been associated with exacerbation of polydipsia, whereas clozapine has been associated with its improvement. The efficacy of risperidone in the treatment of this condition is controversial, as negative results have been reported. Herein we present a schizophrenia case with polydipsia and hyponatremia that was successfully treated with risperidone.
Topics: Adult; Antipsychotic Agents; Female; Humans; Hyponatremia; Obesity; Polydipsia, Psychogenic; Risperidone; Schizophrenia
PubMed: 21638234
DOI: No ID Found -
Endocrine Practice : Official Journal... 2011To report a patient with idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH) who developed profound aquaresis with symptomatic extracellular... (Review)
Review
OBJECTIVE
To report a patient with idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH) who developed profound aquaresis with symptomatic extracellular fluid depletion after initiation of therapy with tolvaptan who was later successfully treated with smaller doses of compounded tolvaptan to prevent rapid correction of serum sodium.
METHODS
Case report and review of the literature.
RESULTS
A 51-year-old woman was diagnosed with SIADH during admission for elective surgery resulting in multiple complications. The patient failed multiple therapies including fluid restriction, salt tablets, and demeclocycline. She was admitted to the hospital for initiation of tolvaptan therapy. After a 15-mg dose of tolvaptan, the patient had rapid increase in urine output and symptomatic hypotension. Sodium levels corrected rapidly overnight from 126 mEq/L to 139 mEq/L. A lower dose of tolvaptan resulted in similar symptoms and sodium correction. Due to continuing symptoms of hyponatremia including headaches, nausea, vomiting, and paresthesias after reinitiation of fluid restriction and salt tablets, tolvaptan was compounded to continue to titrate at lower doses. The patient was then admitted and tolvaptan was initiated at a dose of 1.5 mg with no significant improvement in sodium levels. Tolvaptan was titrated to 3 mg, which resulted in correction of sodium to 129 mEq/L with no associated symptoms of hypovolemia.
CONCLUSIONS
Tolvaptan should be initiated in an inpatient setting with close monitoring of serum sodium levels. In patients who are not able to tolerate recommended dosages, consideration should be given to using a compounded formulation to further titrate to lower doses.
Topics: Benzazepines; Drug Administration Schedule; Female; Humans; Inappropriate ADH Syndrome; Middle Aged; Tolvaptan
PubMed: 21613055
DOI: 10.4158/EP10386.CR -
Australian Dental Journal Sep 2010The aim of this study was to investigate the antimicrobial effect of endodontic medicaments and their bases in the presence of dentine powder.
BACKGROUND
The aim of this study was to investigate the antimicrobial effect of endodontic medicaments and their bases in the presence of dentine powder.
METHODS
The medicaments tested were Ledermix paste, Pulpdent paste, a 50:50 combination of the Pulpdent:Ledermix and their bases. The test organism was Enterococcus faecalis ATCC 29212. The presence or absence of dentine was examined as well as the effect of autoclaving dentine. Serial dilutions of samples at 1 hour, 1 day and 3 days were used for colony counting. The effects of dentine powder on pH for saturated Ca(OH)2 solution and Pulpdent paste at 1 hour and 24 hours were also measured.
RESULTS
Pulpdent and the 50:50 combination of Pulpdent:Ledermix completely inhibited the growth of E. faecalis from 1 hour onwards, and these results were not affected by the presence/absence of dentine powder, pre-incubation period, timing of autoclaving, or exposure time. Saturated solutions of Ca(OH)2 are prone to inactivation by dentine powder unlike Pulpdent paste. Ledermix paste took 3 days to exert a significant effect on the growth of E. faecalis.
CONCLUSIONS
In this laboratory study, both Pulpdent and the 50:50 mixture of Pulpdent with Ledermix were effective medicaments against E. faecalis in the presence of dentine powder.
Topics: Adult; Anti-Infective Agents; Bacterial Load; Calcium Hydroxide; Demeclocycline; Dentin; Disinfection; Drug Combinations; Enterococcus faecalis; Humans; Hydrogen-Ion Concentration; Materials Testing; Methylcellulose; Particle Size; Pharmaceutical Vehicles; Polyethylene Glycols; Root Canal Irrigants; Solubility; Solutions; Time Factors; Triamcinolone Acetonide; Water
PubMed: 20887518
DOI: 10.1111/j.1834-7819.2010.01238.x