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The Journal of Clinical Endocrinology... Oct 2021In patients with cancer, hyponatremia is associated with increased morbidity and mortality and can delay systemic therapy.
CONTEXT
In patients with cancer, hyponatremia is associated with increased morbidity and mortality and can delay systemic therapy.
OBJECTIVE
To assess the safety and efficacy of low-dose tolvaptan (7.5 mg) for hospitalized, adult patients with hyponatremia due to syndrome of inappropriate antidiuresis (SIAD), and coexisting malignancy.
METHODS
Retrospective evaluation in a tertiary cancer center.
RESULTS
Fifty-five patients with mean baseline serum sodium (sNa) 117.9 ± 4.6 mmol/L were included. In total, 90.9% had severe hyponatremia (sNa < 125 mmol/L). Mean age was 65.1 ± 9.3 years. Following an initial dose of tolvaptan 7.5 mg, median (range) increase in sNa observed at 24 hours was 9 (1-19) mmol/L. Within 1 week, 39 patients (70.9%) reached sNa ≥ 130 mmol/L and 48 (87.3%) had sNa rise of ≥5 mmol/L within 48 hours. No severe adverse events were reported. Thirty-three (60%) and 17 (30.9%) patients experienced sNa rise of ≥8 and ≥12 mmol/L/24 hours, respectively. The rate of sNa correction in the first 24 hours was significantly higher among participants that continued fluid restriction after tolvaptan administration (median [quantiles]: 14 [9-16] versus 8 [5-11] mmol/L, P = .036). Moreover, in the over-rapid correction cohort (≥12 mmol/L/24 hours) demeclocycline was appropriately discontinued only in 60% compared with 91.7% of the remaining participants (P = .047). Lower creatinine was predictive of higher sNa correction rate within 24 hours (P = .01).
CONCLUSION
In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatremia due to SIAD in cancer patients, a significant proportion experienced over-rapid correction. Concurrent administration of demeclocycline and/or fluid restriction must be avoided due to the increased risk of over-rapid correction.
Topics: Aged; Antidiuretic Hormone Receptor Antagonists; Female; Follow-Up Studies; Humans; Hyponatremia; Male; Neoplasms; Prognosis; Retrospective Studies; Tolvaptan
PubMed: 33693944
DOI: 10.1210/clinem/dgab131 -
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 -
Journal of Experimental Orthopaedics Jul 2024Establishing zonal tendon-to-bone attachment could accelerate the anterior cruciate ligament reconstruction (ACLR) rehabilitation schedule and facilitate an earlier...
PURPOSE
Establishing zonal tendon-to-bone attachment could accelerate the anterior cruciate ligament reconstruction (ACLR) rehabilitation schedule and facilitate an earlier return to sports. KI24RGDS is a self-assembling peptide hydrogel scaffold (SAPS) with the RGDS amino acid sequence. This study aimed to elucidate the therapeutic potential of KI24RGDS in facilitating zonal tendon-to-bone attachment after ACLR.
METHODS
Sixty-four C57BL/6 mice were divided into the ACLR + SAPS and ACLR groups. ACLR was performed using the tail tendon. To assess the maturation of tendon-to-bone attachment, we quantified the area of mineralized fibrocartilage (MFC) in the tendon graft with demeclocycline. Immunofluorescence staining of α-smooth muscle actin (α-SMA) was performed to evaluate progenitor cell proliferation. The strength of tendon-to-bone attachment was evaluated using a pull-out test.
RESULTS
The MFC and maximum failure load in the ACLR + SAPS group were remarkably higher than in the ACLR group on Day 14. However, no significant difference was observed between the two groups on Day 28. The number of α-SMA-positive cells in the tendon graft was highest on Day 7 after ACLR in both the groups and was significantly higher in the ACLR + SAPS group than in the ACLR group.
CONCLUSION
This study highlighted the latent healing potential of KI24RGDS in facilitating early-stage zonal attachment of tendon grafts and bone tunnels post-ACLR. These findings may expedite rehabilitation protocols and shorten the timeline for returning to sports.
LEVEL OF EVIDENCE
Not applicable.
PubMed: 38899049
DOI: 10.1002/jeo2.12061 -
Journal of Clinical Research in... Sep 2017Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus... (Review)
Review
Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus indicated, even in asymptomatic patients. The conventional treatment consists of fluid restriction in presence of euvolemia or hypervolemia; loop diuretics are used in some hypervolemic conditions such as cardiac heart failure, liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic solutions are administered in hypovolemic conditions. The utilization of demeclocycline and urea is not indicated in pediatric ages due to lack of data on their toxicity and poor tolerance. Recently, a new therapeutic option has been developed, a class of non-peptide arginine vasopressin receptor antagonists called vaptans. Tolvaptan is the only such agent approved in Europe for the treatment of hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are so far available in paediatric patients, since only one trial has been registered in Europe which includes children and adolescents, but this trial is still ongoing. Here, we report three children with chronic hyponatremia due to SIADH in which tolvaptan has been used successfully.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Child; Child, Preschool; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Tolvaptan
PubMed: 28515029
DOI: 10.4274/jcrpe.4531 -
Talanta Feb 2021In this paper, for the first time, the study of voltammetric determination of tetracycline antibiotic demeclocycline was conducted. The oxidation of compound was...
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 (2.3 × 10 M) for 4 × 10 SDS-containing buffer solution at pH 2, and 0.24 μg mL (4.8 × 10 M) for 1 × 10 CTAB-containing buffer solution at pH 9.0. The feasibility of the developed approach for the quantification of demeclocycline was tested in urine samples.
Topics: Anti-Bacterial Agents; Boron; Demeclocycline; Diamond; Electrodes; Surface-Active Agents
PubMed: 33303147
DOI: 10.1016/j.talanta.2020.121695 -
Food Additives & Contaminants. Part A,... 2015Antibacterials are widely used in veterinary medicine. Residues of these drugs can remain in food of animal origin, including bovine liver. This paper describes a fast...
Antibacterials are widely used in veterinary medicine. Residues of these drugs can remain in food of animal origin, including bovine liver. This paper describes a fast and simple analytical method for the determination of quinolones and fluoroquinolones, tetracyclines and sulfonamides in bovine liver samples. Deuterated enrofloxacin, sulfapyridine and demeclocycline were used as internal standards. The homogenised liver samples were extracted with acidified acetonitrile. Steps of non-solid-phase extraction (SPE) clean-up and concentration were used in the presented method. The final extracts were analysed by sensitive and selective detection of all components in a single run using LC-MS/MS. Acceptable recoveries between 66% and 110% were obtained. Good linearity (r(2)) above 0.96, considering three different days, for all drugs was achieved in concentrations ranging from 0.0 to 2.0 × the maximum residue limit (MRL). Intraday precision with coefficient of variation (CV%) (n = 6) lower than 14.7% and inter-day precision lower than 18.8% in agreement with European Commission Decision 2002/657/EC were obtained in concentrations ranging from 0.5 to 1.5 MRL. Accuracy was between 86% and 110%. Limits of detection and quantitation, as well as decision limit (CCα) and detection capability (CCβ), were also evaluated.
Topics: Animals; Anti-Bacterial Agents; Cattle; Chromatography, Liquid; Drug Residues; Fluoroquinolones; Liver; Poultry; Quinolones; Sulfonamides; Swine; Tandem Mass Spectrometry; Tetracyclines; Veterinary Drugs
PubMed: 25686359
DOI: 10.1080/19440049.2015.1007091 -
JBMR Plus Jul 2019Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced...
Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced bone turnover, which can limit the ability of bone to release or store calcium, potentially leading to low, normal, or high serum calcium levels. We describe a 51-year-old dialysis-dependent female with hypercalcemia after parathyroidectomy. A demeclocycline-labeled bone biopsy confirmed adynamic bone disease. Teriparatide, a recombinant form of parathyroid hormone (PTH) used to treat postmenopausal osteoporosis, was prescribed for 12 months and normalized serum calcium levels. Although previous case reports and series have described favorable changes in spine bone mineral density when teriparatide was prescribed for ABD, ours is the first documented case in which teriparatide resolved hypercalcemia due to ABD. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
PubMed: 31372586
DOI: 10.1002/jbm4.10176 -
Journal of the Science of Food and... Sep 2018Antibiotic drugs are excreted to a large proportion by livestock. Thus, antibiotics are distributed on fields with slurry and can be taken up by plants. In the present...
BACKGROUND
Antibiotic drugs are excreted to a large proportion by livestock. Thus, antibiotics are distributed on fields with slurry and can be taken up by plants. In the present study, hydroponic experiments were performed to reveal whether the widely administered chlortetracycline is taken up into wheat grain in a concentration-dependent manner. A further goal was to determine (chlor)tetracyclines in wheat and rye grain from agricultural practice.
RESULTS
Increasing chlortetracycline deposition in wheat grain was observed with a rising chlortetracycline spiking level in the hydroponic solution. In 371 selected wheat and rye samples from three growing years of agricultural practice, the overall detection frequency was 21% for tetracyclines. In the most highly contaminated sample, tetracyclines occurred at 18.2 μg kg . Tetracycline residues were also found in rye grain. Conversion and degradation products of (chlor)tetracycline such as tetracycline, doxycycline and demeclocycline were detected in grains from hydroponic experiments and from agricultural practice.
CONCLUSION
Concentrations of tetracyclines found in wheat and rye grains were of no concern with respect to toxicity regarding human consumption. However, antibiotic concentrations below the minimum inhibitory concentration can select for antibiotic resistance in bacteria. Thus, low levels of different tetracycline residues contained in food should be taken into account regarding risk assessment. © 2018 Society of Chemical Industry.
Topics: Anti-Bacterial Agents; Chlortetracycline; Consumer Product Safety; Drug Residues; Food Contamination; Humans; Secale; Seeds; Tetracyclines; Triticum
PubMed: 29484666
DOI: 10.1002/jsfa.8982 -
Drug Testing and Analysis Jul 2022Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and...
Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and wound infections in cattle and swine. The present work proposes a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for oxytetracycline quantification in bull plasma, seminal plasma and urine, requiring limited sample treatment before analysis. Extraction with trichloroacetic acid followed by dilution of the supernatant in mobile phase proved to be effective in all three matrices, allowing to rapidly process large batches of samples. Sharp and symmetrical peak shape was obtained using a BEH C18 reversed-phase column in a chromatographic run of just 3.5 min. The mass spectrometer operated in positive electrospray ionization mode and monitored specific transitions for oxytetracycline (461.1 → 425.8) and the internal standard demeclocycline (465.0 → 447.6). The method was validated over concentration ranges suitable for field concentrations of oxytetracycline found in each matrix, showing good linearity during each day of testing (R always >0.99), as also confirmed by analysis of variance (ANOVA) and lack-of-fit tests. Excellent accuracy and precision were demonstrated by calculated bias always within ±15% and CV% below 10% at all quality control (QC) levels in the three matrices. Matrix effect and recovery were investigated for both analytes, which showed consistent and comparable behaviour in each matrix. To our knowledge, this is the first validated approach for mass spectrometric determination of oxytetracycline in seminal plasma and urine. The method was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to assess the oxytetracycline concentration-time profile in plasma, seminal plasma and urine.
Topics: Animals; Anti-Bacterial Agents; Cattle; Chromatography, High Pressure Liquid; Chromatography, Liquid; Male; Oxytetracycline; Reproducibility of Results; Semen; Spectrometry, Mass, Electrospray Ionization; Swine; Tandem Mass Spectrometry
PubMed: 35195370
DOI: 10.1002/dta.3246