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NDT Plus Nov 2009The syndrome of inappropriate antidiuretic hormone secretion (SIADH) remains a challenging disorder to diagnose and treat. Three cases are presented to illustrate these...
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) remains a challenging disorder to diagnose and treat. Three cases are presented to illustrate these challenges. The first two cases had drug-induced SIADH secondary to a selective serotonin reuptake inhibitor (for depression) or carbamazepine (for trigeminal neuralgia). The third case had SIADH possibly secondary to bronchiectasis. The lowest serum sodium concentrations ranged between 118 and 124 mmol/L in the three cases. Hyponatraemia was not acute and severe symptoms were absent. However, several mild neurological symptoms were present. In the first case, hyponatraemia likely contributed to a fall, which resulted in a fracture of the odontoid process of the axis. The other two cases also had gait disturbances, in addition to nausea, headache, impaired memory, difficulty concentrating and confusion. In at least two of the cases, the underlying cause of SIADH was impossible to reverse. Traditional treatment for SIADH with fluid restriction and demeclocycline failed, caused side effects or increased duration of hospital stay. These examples suggest a need for better treatment options. The introduction of the vasopressin-receptor antagonists for SIADH may be a welcome new therapy to overcome some of these challenges.
PubMed: 19881933
DOI: 10.1093/ndtplus/sfp155 -
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 -
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 -
PloS One 2022Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer...
OBJECTIVE
Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer (EC). Our study aims to detect shared gene signatures and biological mechanism between PCOS and EC by bioinformatics analysis.
METHODS
Bioinformatics analysis based on GEO database consisted of data integration, network construction and functional enrichment analysis was applied. In addition, the pharmacological methodology and molecular docking was also performed.
RESULTS
Totally 10 hub common genes, MRPL16, MRPL22, MRPS11, RPL26L1, ESR1, JUN, UBE2I, MRPL17, RPL37A, GTF2H3, were considered as shared gene signatures for EC and PCOS. The GO and KEGG pathway analysis of these hub genes showed that "mitochondrial translational elongation", "ribosomal subunit", "structural constituent of ribosome" and "ribosome" were highly correlated. Besides, associated transcription factors (TFs) and miRNAs network were constructed. We identified candidate drug molecules including fenofibrate, cinnarizine, propanil, fenthion, clindamycin, chloramphenicol, demeclocycline, hydrochloride, azacitidine, chrysene and artenimol according to these hub genes. Molecular docking analysis verified a good binding interaction of fenofibrate against available targets (JUN, ESR1, UBE2I).
CONCLUSION
Gene signatures and regulatory biological pathways were identified through bioinformatics analysis. Moreover, the molecular mechanisms of these signatures were explored and potential drug molecules associated with PCOS and EC were screened out.
Topics: Computational Biology; Endometrial Neoplasms; Female; Fenofibrate; Gene Regulatory Networks; Humans; Molecular Docking Simulation; Polycystic Ovary Syndrome
PubMed: 35830453
DOI: 10.1371/journal.pone.0271380 -
Pharmaceuticals (Basel, Switzerland) Apr 2023Type 2 diabetes mellitus is a chronic health problem that can be controlled by slowing one's carbohydrate metabolism by inhibiting α-glucosidase, an enzyme responsible...
Type 2 diabetes mellitus is a chronic health problem that can be controlled by slowing one's carbohydrate metabolism by inhibiting α-glucosidase, an enzyme responsible for carbohydrate degradation. Currently, drugs for type 2 diabetes have limitations in terms of safety, efficiency, and potency, while cases are rapidly increasing. For this reason, the study planned and moved towards drug repurposing by utilizing food and drug administration (FDA)-approved drugs against α-glucosidase, and investigated the molecular mechanisms. The target protein was refined and optimized by introducing missing residues, and minimized to remove clashes to find the potential inhibitor against α-glucosidase. The most active compounds were selected after the docking study to generate a pharmacophore query for the virtual screening of FDA-approved drug molecules based on shape similarity. The analysis was performed using (ADV)-based on binding affinities (-8.8 kcal/mol and -8.6 kcal/mol) and root-mean-square-deviation (RMSD) values (0.4 Å and 0.6 Å). Two of the most potent lead compounds were selected for a molecular dynamics (MD) simulation to determine the stability and specific interactions between receptor and ligand. The docking score, RMSD values, pharmacophore studies, and MD simulations revealed that two compounds, namely Trabectedin (ZINC000150338708) and Demeclocycline (ZINC000100036924), are potential inhibitors for α-glucosidase compared to standard inhibitors. These predictions showed that the FDA-approved molecules Trabectedin and Demeclocycline are potential suitable candidates for repurposing against type 2 diabetes. The in vitro studies showed that trabectedin was significantly effective with an IC of 1.263 ± 0.7 μM. Further investigation in the laboratory is needed to justify the safety of the drug to be used in vivo.
PubMed: 37111312
DOI: 10.3390/ph16040555 -
British Medical Journal Jun 1968
Topics: Chloramphenicol; Chlortetracycline; Demeclocycline; Drug Resistance, Microbial; Haemophilus Infections; Humans; Methacycline; Oxytetracycline; Rolitetracycline; Salmonella Infections; Tetracycline
PubMed: 4968330
DOI: No ID Found -
Australian Dental Journal Jun 2018Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy... (Comparative Study)
Comparative Study
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) , Odontopaste, 0.2% chlorhexidine and 50:50 combinations of Ledermix/Ca(OH) and Odontopaste/Ca(OH) ) 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) and 50:50 combinations of Ca(OH) /Ledermix or Ca(OH) /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) in isolation and combined with Ledermix, and Odontopaste was highly effective in reducing bacterial viability.
Topics: Biofilms; Calcium Hydroxide; Chlorhexidine; Demeclocycline; Dental Pulp Cavity; Dentin; Drug Combinations; Enterococcus faecalis; Humans; Microbial Viability; Microscopy, Electron, Scanning; Root Canal Irrigants; Sodium Hypochlorite; Triamcinolone Acetonide
PubMed: 29181844
DOI: 10.1111/adj.12580 -
Frontiers in Cellular and Infection... 2021Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most...
Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against and the zoonotic . In contrast to tetracyclines, boromycin rapidly killed asexual stages of both species already at low concentrations (~ 1 nM) including multidrug resistant strains (Dd2, K1, 7G8). In addition, boromycin was active against stage V gametocytes at a low nanomolar range (IC: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.
Topics: Animals; Anti-Bacterial Agents; Antimalarials; Borates; Malaria, Falciparum; Plasmodium falciparum
PubMed: 35096650
DOI: 10.3389/fcimb.2021.802294 -
ACS Chemical Neuroscience Feb 2023H,N-Heteronuclear Single Quantum Coherence (HSQC) NMR is a powerful technique that has been employed to characterize small-molecule interactions with intrinsically...
H,N-Heteronuclear Single Quantum Coherence (HSQC) NMR is a powerful technique that has been employed to characterize small-molecule interactions with intrinsically disordered monomeric α-Synuclein (aSyn). We report how solution pH can impact the interpretation of aSyn HSQC NMR spectra and demonstrate that small-molecule formulations (e.g., complexation with acidic salts) can lower sample pH and confound interpretation of drug binding and concomitant protein structural changes. Through stringent pH control, we confirm that several previously identified compounds (EGCG, Baicalin, and Dopamine (DOPA)) as well as a series of potent small-molecule inhibitors of aSyn pathology (Demeclocycline, Ro90-7501, and (±)-Bay K 8644) are capable of direct target engagement of aSyn. Previously, DOPA-aSyn interactions have been shown to elicit a dramatic chemical shift perturbation (CSP) localized to aSyn's H50 at low DOPA concentrations then expanding to aSyn's acidic C-terminal residues at increasing DOPA levels. Interestingly, this CSP profile mirrors our pH titration, where a small reduction in pH affects H50 CSP, and large pH changes induce robust C-terminal CSP. In contrast, under tightly controlled pH 5.0, DOPA induces significant CSPs observed at both ionizable and nonionizable residues. These results suggest that previous interpretations of DOPA-aSyn interactions were conflated with pH-induced CSP, highlighting the need for stringent pH control to minimize potential false-positive interpretations of ligand interactions in HSQC NMR experiments. Furthermore, DOPA's preferential interaction with aSyn under acidic pH represents a novel understanding of DOPA-aSyn interactions that may provide insight into the potential gain of toxic function of aSyn misfolding in α-synucleinopathies.
Topics: alpha-Synuclein; Dihydroxyphenylalanine; Hydrogen-Ion Concentration; Nuclear Magnetic Resonance, Biomolecular; Small Molecule Libraries
PubMed: 36749138
DOI: 10.1021/acschemneuro.2c00782 -
British Medical Journal (Clinical... Sep 1982
Clinical Trial
Topics: Adult; Aged; Celiac Disease; Demeclocycline; Feces; Female; Humans; Male; Middle Aged; Tetracycline
PubMed: 6810999
DOI: 10.1136/bmj.285.6344.780