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Life Sciences Sep 2020The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted...
The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (M). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 M crystal structure. Molecular docking simulation predicted the docking score >-7 kcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 M. The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 M which can used in combinational therapy against SARS-CoV-2 infection.
Topics: Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Binding Sites; COVID-19; Computational Biology; Coronavirus Infections; Databases, Genetic; Humans; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Peptide Hydrolases; Pneumonia, Viral; Protease Inhibitors; Protein Binding; SARS-CoV-2; Tetracyclines; Viral Nonstructural Proteins
PubMed: 32653520
DOI: 10.1016/j.lfs.2020.118080 -
European Endodontic Journal Oct 2022To explore the long-term effects on discolouration by demeclocycline HCl (Ledermix, LED) or doxycycline hyclate (Doxymix, DOX) pastes placed in extracted human teeth...
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.
Topics: Demeclocycline; Doxycycline; Drug Combinations; Humans; Polyethylene Glycols; Root Canal Irrigants; Tetracyclines; Triamcinolone Acetonide
PubMed: 36217644
DOI: 10.14744/eej.2022.07108 -
The Cochrane Database of Systematic... Feb 2019Traumatic 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Bone Development; Calcium Hydroxide; Demeclocycline; Drug Combinations; Humans; Hyperbaric Oxygenation; Incisor; Periodontal Ligament; Preoperative Care; Randomized Controlled Trials as Topic; Root Canal Irrigants; Tooth Avulsion; Tooth Discoloration; Tooth Replantation; Triamcinolone Acetonide
PubMed: 30720860
DOI: 10.1002/14651858.CD006542.pub3 -
Cureus Apr 2022Hyponatraemia is the most common electrolyte abnormality encountered in the inpatient setting and is associated with increased morbidity, mortality, and length of...
Hyponatraemia is the most common electrolyte abnormality encountered in the inpatient setting and is associated with increased morbidity, mortality, and length of hospital stay. Syndrome of inappropriate anti-diuresis (SIAD) remains the most common cause. Hyponatraemia due to SIAD presents various challenges in treatment approaches, including poor concordance (e.g., to fluid restriction), medication intolerance (e.g., demeclocycline), and risk of rapid sodium shifts (e.g., with vaptan therapy). The use of oral sodium chloride (NaCl) tablets is a recognised treatment approach. However, it is not commonly advocated. We present the cases of two elderly patients in whom the temporary use of NaCl tablets, as an adjunct to fluid restriction, led to safe and effective correction of SIAD-related hyponatraemia with resultant reduced length of hospital admission.
PubMed: 35475246
DOI: 10.7759/cureus.24367 -
Frontiers in Pediatrics 2021Suprasellar arachnoid cysts represent a rare occurrence in the pediatric population and usually cause symptoms related to mass effect and can occasionally cause...
Suprasellar arachnoid cysts represent a rare occurrence in the pediatric population and usually cause symptoms related to mass effect and can occasionally cause endocrine dysfunctions. The association between SAC and the syndrome of inappropriate antidiuretic hormone (SIADH) in the pediatric population has rarely been described previously. In most cases, SIADH is temporary and resolves by treating the underlying cause. The first-line treatment consists of fluid restriction in asymptomatic children. Oral urea and demeclocycline are other effective treatment options. Vaptans are a new class of medication for the management of SIADH. These agents are a nonpeptide vasopressin V2 receptor antagonist that selectively antagonizes the antidiuretic effect of AVP, resulting in excretion of diluted urine or "aquaresis." Their efficacy has been shown in adult patients with euvolemic or hypervolemic hyponatremia. However, evidence is lacking in pediatric patients with SIADH. We report the case of a 9-year-old female child with a SAC, who underwent endoscopic fenestration at the age of 2 years. After surgery she developed chronic hyponatremia due to SIADH. Hyponatremia was refractory to treatment with fluid restriction, oral sodium, and urea. In order to normalize serum sodium levels, tolvaptan treatment was started on a compassionate-use basis; 24-48 h later serum sodium levels returned to normal. To date, tolvaptan has been used regularly for 6 years with no side effects occurring during the treatment period. This is the first case of a child with chronic SIADH secondary to SAC successfully treated with tolvaptan. Further studies are needed to demonstrate its usefulness on a broader case series.
PubMed: 34336740
DOI: 10.3389/fped.2021.684131 -
Food Frontiers Jun 2020Angiotensin converting enzyme 2 (ACE2) and main protease (M) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in...
Angiotensin converting enzyme 2 (ACE2) and main protease (M) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome-coronaviruses or SARS-CoV genome. In the present study, we identified 11 potent bioactive compounds from ethanolic leaf extract of (L.) by using GC-MS analysis. These potential bioactive compounds were considered for molecular docking studies against ACE2 and M target proteins to determine the antiviral effects against SARS-COV. Results exhibits that among 11 compounds from (L.), urso-deoxycholic acid, demeclocycline, tetracycline, chlorotetracycline, and ethyl iso-allocholate had potential viral inhibitory activity. Hence, the present findings suggested that chemical constitution present in (L.) will address inhibition of corona viral replication in host cells.
PubMed: 32838301
DOI: 10.1002/fft2.29 -
Acta Biochimica Et Biophysica Sinica Dec 20176-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of...
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%.
Topics: Anti-Bacterial Agents; Demeclocycline; Multigene Family; Recombination, Genetic; Streptomyces aureofaciens
PubMed: 29087452
DOI: 10.1093/abbs/gmx110 -
Oncotarget Dec 2016Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular... (Comparative Study)
Comparative Study
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.
Topics: Animals; Anthraquinones; Connective Tissue; Demeclocycline; Disease Progression; Fluoresceins; Fluorescent Dyes; Genetic Predisposition to Disease; Heterozygote; Homozygote; Mice, Inbred BALB C; Mice, Mutant Strains; Microscopy, Fluorescence; Mutation; Phenotype; Phosphoric Diester Hydrolases; Pyrophosphatases; Time Factors; Vascular Calcification
PubMed: 27863377
DOI: 10.18632/oncotarget.13335 -
ADMET & DMPK 2020The bioavailability of tetracyclines is markedly decreased when co-administered with antacids, milk, or food containing Ca. Previously, it was suggested that the...
The bioavailability of tetracyclines is markedly decreased when co-administered with antacids, milk, or food containing Ca. Previously, it was suggested that the effective intestinal permeation of tetracycline (TC) was decreased due to Ca linked mucin binding in the mucosal side. In the present study, we investigated the effect of Ca, Mg, and mucin on the membrane permeation of six tetracyclines (TC, oxytetracycline (OTC), minocycline (MINO), doxycycline (DOXY), demeclocycline (DMCTC), and chlortetracycline (CTC)). The membrane permeability values (P) of tetracyclines were measured by the parallel artificial membrane permeation assay (PAMPA) using soybean lecithin - decane (SL-PAMPA) and octanol (OCT-PAMPA) membranes. In SL-PAMPA, Ca markedly decreased the P values of all tetracyclines. In OCT-PAMPA, Ca increased the P values of TC, CTC, and DMCTC, but not DOXY, OTC, and MINO. Mg decreased the P values of all tetracyclines in both SL-PAMPA and OCT-PAMPA (except for CTC in OCT-PAMPA). The addition of mucin had little or no effect in all cases. In contrast to the previously suggested mechanism, the results of the present study suggested that Ca chelate formation decreased the membrane permeation of tetracyclines, irrespective of Ca linked mucin binding. Molecular speciation analysis suggested that the permeation of TC - metal chelates was negligibly small in SL-PAMPA.
PubMed: 35300369
DOI: 10.5599/admet.797 -
Cureus May 2018We present the case of a 55-year-old Caucasian male with a history of schizophrenia presenting with severe hyponatremia attributed to long-acting injectable risperidone...
We present the case of a 55-year-old Caucasian male with a history of schizophrenia presenting with severe hyponatremia attributed to long-acting injectable risperidone treatment. Antipsychotic-induced hyponatremia is an uncommon but serious side effect that should be considered when assessing individuals on chronic psychiatric regimens. In this report, we will discuss our treatment plan for the patient when water deprivation and hypertonic saline failed to correct his serum sodium levels. The goal of this case report is to raise awareness of severe hyponatremia as a side effect of long-acting risperidone, and to encourage further studies to create guidelines for its management when current protocols fail to correct sodium levels.
PubMed: 30042908
DOI: 10.7759/cureus.2657