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1.
Clin Case Rep ; 12(4): e8779, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634093

RESUMO

Key Clinical Message: Even in the absence of other symptoms or other pulmonary manifestations suggesting Sjögren's syndrome (SS), it is necessary to include SS in the differential diagnosis of diffuse cystic lung disease (CLD). Abstract: A case of SS that presented initially with diffuse CLD is reported. This case is considered rare because diffuse pulmonary cysts were observed in the early stage with few symptoms, only cysts were observed without other lung lesions on imaging, cyst formation was histologically considered to be alveolar loss, and airway lesions not observed on imaging were suspected based on lung function testing. The details of this case provide extremely important information to consider for the diagnosis and management of CLD and SS.

2.
J Vet Pharmacol Ther ; 47(1): 21-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37753811

RESUMO

This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain model approach, irrelevant plasma and urine TXA concentrations were estimated to be 0.0206 and 0.997 µg/mL, respectively. The typical values of clearance, steady-state volume of distribution, and steady-state urine-to-plasma ratio were 0.080 L/kg/h, 0.86 L/kg, and 49.0, respectively. The obtained irrelevant concentrations will be useful for establishing relevant regulatory screening limits for effective control of TXA use in horse racing and equestrian sports.


Assuntos
Líquidos Corporais , Esportes , Ácido Tranexâmico , Cavalos , Animais , Feminino , Ácido Tranexâmico/farmacocinética , Ácido Tranexâmico/uso terapêutico , Cromatografia Líquida/veterinária
3.
Artigo em Inglês | MEDLINE | ID: mdl-37930044

RESUMO

OBJECTIVES: The use of bone wax (BW) is controversial for sternal haemostasis because it increases the risk of wound infection and inhibits bone healing. We developed new waxy bone haemostatic agents made from biodegradable polymers containing peptides and evaluated them using rabbit models. METHODS: We designed 2 types of waxy bone haemostatic agents: peptide wax (PW) and non-peptide wax (NPW), which used poly(ε-caprolactone)-based biodegradable polymers with or without an osteogenesis-enhancing peptide, respectively. Rabbits were randomly divided into 4 groups based on treatment with BW, NPW, PW or no treatment. In a tibial defect model, the bleeding amount was measured and bone healing was evaluated by micro-computed tomography over 16 weeks. Bone healing in a median sternotomy model was assessed for 2 weeks using X-ray, micro-computed tomography, histological examination and flexural strength testing. RESULTS: The textures of PW and NPW (n = 12 each) were similar to that of BW and achieved a comparable degree of haemostasis. The crevice area of the sternal fracture line in the BW group was significantly larger than that in other groups (n = 10 each). The PW group demonstrated the strongest sternal flexural strength (n = 10), with complete tibial healing at 16 weeks. No groups exhibited wound infection, including osteomyelitis. CONCLUSIONS: Waxy biodegradable haemostatic agents showed satisfactory results in haemostasis and bone healing in rabbit models and may be an effective alternative to BW.

4.
Nagoya J Med Sci ; 85(3): 626-634, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37829491

RESUMO

At our hospital, we are conducting the "Clinical Study of a Patient-Specific Cardiac Support Net for Dilated Cardiomyopathy (jRCTs042180025)", a multi-facility clinical study of a customized cardiac support net (CSN). Here, we describe the cardiac rehabilitation (CR) of a heart failure (HF) patient after CSN treatment. The patient was a 65-year-old man who exhibited dilated cardiomyopathy (DCM) because of left ventricular non-compaction; his New York Heart Association status was class III. In November 2019, he received CSN treatment. The early CR program was adapted for this patient, and his postoperative course was uneventful. Functional measurements showed improved leg-muscle strength (before treatment: 61.4% BW; at discharge: 77.3% BW). During long-term follow-up, the patient's exercise tolerance increased, as shown by 6-minute walk distance (before treatment: 576 m; long-term follow-up: 600 m) and peak oxygen uptake (before treatment: 12.5 mL/kg/min; long-term follow-up: 13.3 mL/kg/min). In the 2 years since discharge, the patient has not been hospitalized for HF. This report is the first to show that the CSN can be used to perform a CR program in a DCM patient without significant functional decline.


Assuntos
Reabilitação Cardíaca , Cardiomiopatia Dilatada , Insuficiência Cardíaca , Masculino , Humanos , Idoso , Reabilitação Cardíaca/efeitos adversos , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/cirurgia , Alta do Paciente , Tolerância ao Exercício/fisiologia
5.
J Anal Toxicol ; 47(7): 623-631, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37632695

RESUMO

Vadadustat is a newly launched hypoxia-inducible factor stabilizer with anti-anemia and erythropoietic effects; however, its use in horses is expressly forbidden in both racing and equestrian competitions. Following our previous report on the pharmacokinetic study of vadadustat in horse plasma and urine, a long-term longitudinal analysis of vadadustat in horse hair after nasoesophageal administration (3 g/day for 3 days) to three thoroughbred mares is described in this study. Our main objective is to further extend the detection period of vadadustat for the purpose of doping control. Three bunches of mane hair from each horse were collected at 0 (pre), 1, 2, 3 and 6 month(s) post-administration. These hair samples were each cut into 2-cm segments and pulverized after decontamination of hair samples. The analyte in the powdered hair samples was extracted with liquid-liquid extraction followed by further purification by solid-phase extraction with strong anion exchange columns. The amount of vadadustat incorporated into the hair was quantified with a newly developed and validated method using liquid chromatography-high-resolution mass spectrometry. Our results show that vadadustat was confirmed in all post-administration hair samples, but its metabolites were not present. Thus, the detection window for vadadustat could be successfully extended up to 6 months post-administration. Interestingly, the 2-cm segmental analysis revealed that the tip of the drug band in the hair shifted along with the hair shafts in correspondence with the average hair growth rate (∼2.5 cm/month) but gradually diffused more widely from 2 cm at 1 month post-administration to up to 14 cm at 6 months post-administration. However, the loss in the total amount of vadadustat in hair over time was observed to most likely be due to the degradation of vadadustat. These findings will be useful for the control of abuse and/or misuse of vadadustat and the interpretation of positive doping cases.


Assuntos
Líquidos Corporais , Glicina , Animais , Feminino , Cavalos , Cromatografia Líquida , Cabelo
6.
J Pharm Biomed Anal ; 235: 115600, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37516063

RESUMO

Daprodustat is a hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) inhibitor and is used as an erythropoiesis stimulant for the treatment of anemia in humans. In general, administering daprodustat to horses will result in a lifetime ban from both equestrian sports and horseracing by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale, respectively. To control the misuse/abuse of daprodustat, we conducted nasoesophageal administration of daprodustat (100 mg/day for 3 days) to three thoroughbred mares and the post-administration hair samples collected from the three horses over 6 months were analyzed to demonstrate the potential longer-term detection of daprodustat and its metabolites in hair compared with the detection times of daprodustat of 1 and 2 weeks in plasma and urine respectively. The results of the quantitative 2-cm segmental analysis showed that daprodustat was primarily localized in the proximal region (0-2 cm) at 0.375-0.463 pg/mg at 1 month post-administration. These drug bands were gradually spread out along the hair shaft at a rate consistent with the reported growth rate of horse mane hair (approximately 2.5 cm/month) over the following 6 months. In addition, to attain deeper insight into the mechanism of drug incorporation into hair, a total of 11 relevant parameters, including the actual PK parameters and simulated physicochemical and biopharmaceutical parameters for three HIF stabilizers (i.e., daprodustat, vadadustat, and IOX4), were investigated after normalization of the z-scores of all these parameters. Multiple regression analysis indicated that the major factors contributing to the incorporation of the three drugs into hair were their maximum plasma concentrations and lipophilicities, strongly suggesting that the three HIF stabilizers permeated from the bloodstream into the hair bulb via passive transfer with concentration gradients. This work is the first reported evidence showing the incorporation of HIF stabilizers into hair via passive transfer. In addition, cross-species comparison of drug incorporations into hair between daprodustat in horse and roxadustat in human was made in order to have a better understanding of the interactive interpretations about the analysis results obtained from different species. The above findings are not only useful and beneficial for the purpose of doping control but also provide a better understanding of the mechanism of drug incorporation into horse hair.


Assuntos
Anemia , Barbitúricos , Humanos , Cavalos , Animais , Feminino , Barbitúricos/análise , Barbitúricos/uso terapêutico , Anemia/tratamento farmacológico , Cabelo/química , Hipóxia/tratamento farmacológico , Prolina Dioxigenases do Fator Induzível por Hipóxia/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/uso terapêutico
7.
Arch Gerontol Geriatr ; 115: 105111, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37421690

RESUMO

BACKGROUND: The early recognition of hospitalized patients at risk of being discharged to long-term care facilities (LTCFs) may help to identify those who require transitional care programs and interventions that support discharge to home. We examined the association of functional and cognitive impairment severity with discharge to LTCFs among older hospitalized patients. METHODS: In this retrospective cohort study, we used an administrative claims database linked with geriatric assessment data from a general acute care hospital in Japan. We analyzed patients aged ≥65 years discharged between July 2016 and December 2018. The severity of functional and cognitive impairments was assessed using the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) scale. Based on their DASC-8 scores, patients were designated as Category I (no impairment), Category Ⅱ (mild impairment), or Category III (moderate/severe impairment). We conducted logistic regression analyses to examine the association between the severity of impairments and discharge to LTCFs after adjusting for patient-level factors. RESULTS: We analyzed 9,060 patients (mean age: 79.4 years). Among the 112 patients (1.2%) discharged to LTCFs, 62.3%, 18.6%, and 19.2% fell under Category I, Category Ⅱ, and Category III, respectively. Category II was not significantly associated with discharge to LTCFs. However, Category III had a significantly higher odds of discharge to LTCFs than Category I (Adjusted odds ratio: 2.812, 95% confidence interval: 1.452-5.449). CONCLUSION: Patients identified as Category III by the DASC-8 on admission may benefit from enhanced transitional care and interventions that promote discharge to home.


Assuntos
Disfunção Cognitiva , Alta do Paciente , Humanos , Idoso , Estudos Retrospectivos , Assistência de Longa Duração , Disfunção Cognitiva/epidemiologia , Hospitais
8.
Innov Aging ; 7(5): igad043, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342490

RESUMO

Background and Objectives: Readmission-related health care reforms have shifted their focus from all-cause readmissions (ACR) to potentially avoidable readmissions (PAR). However, little is known about the utility of analytic tools from administrative data in predicting PAR. This study determined whether 30-day ACR or 30-day PAR is more predictable using tools that assess frailty, comorbidities, and activities of daily living (ADL) from administrative data. Research Design and Methods: This retrospective cohort study was conducted at a large general acute care hospital in Tokyo, Japan. We analyzed patients aged ≥70 years who had been admitted to and discharged from the subject hospital between July 2016 and February 2021. Using administrative data, we assessed each patient's Hospital Frailty Risk Score, Charlson Comorbidity Index, and Barthel Index on admission. To determine the influence of each tool on readmission predictions, we constructed logistic regression models with different combinations of independent variables for predicting unplanned ACR and PAR within 30 days of discharge. Results: Among 16 313 study patients, 4.1% experienced 30-day ACR and 1.8% experienced 30-day PAR. The full model (including sex, age, annual household income, frailty, comorbidities, and ADL as independent variables) for 30-day PAR showed better discrimination (C-statistic: 0.79, 95% confidence interval: 0.77-0.82) than the full model for 30-day ACR (0.73, 0.71-0.75). The other prediction models for 30-day PAR also had consistently better discrimination than their corresponding models for 30-day ACR. Discussion and Implications: PAR is more predictable than ACR when using tools that assess frailty, comorbidities, and ADL from administrative data. Our PAR prediction model may contribute to the accurate identification of at-risk patients in clinical settings who would benefit from transitional care interventions.

10.
J Pers Med ; 13(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37109016

RESUMO

Impella 5.0 circulatory support via subclavian artery (SA) access may be a safe approach for patients undergoing cardiac rehabilitation (CR). In this case series, we retrospectively analyzed the demographic characteristics, physical function, and CR data of six patients who underwent Impella 5.0 implantation via the SA prior to left ventricular assist device (LVAD) implantation between October 2013 and June 2021. The median age was 48 years, and one patient was female. Grip strength was maintained or increased in all patients before LVAD implantation (pre-LVAD) compared to after Impella 5.0 implantation. The pre-LVAD knee extension isometric strength (KEIS) was less than 0.46 kgf/kg in two patients and more than 0.46 kgf/kg in three patients (unavailable KEIS data, n = 1). With Impella 5.0 implantation, two patients could ambulate, one could stand, two could sit on the edge of the bed, and one remained in bed. One patient lost consciousness during CR due to decreased Impella flow. There were no other serious adverse events. Impella 5.0 implantation via the SA allows mobilization, including ambulation, prior to LVAD implantation, and CR can be performed relatively safely.

11.
Artif Organs ; 47(2): 387-395, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36269680

RESUMO

BACKGROUND: We evaluated the impact of a standardized driveline care strategy, including a subfascial-tunneling method and dressing protocol, on the incidence of driveline infection (DLI). METHODS: DLI data from all HeartMate II (HMII) and HeartMate 3 (HM3) patients (including exchange devices) were retrospectively collected between 2013 and 2021. The driveline subfascial-tunneling method was altered in three steps (A: right direct; B: left triple, C: right triple), and the shower protocol was changed in two steps (A: with/without cover, B: with cover). Disinfection was individually tailored after changing the shower protocol. Complications associated with morbidity and mortality were evaluated for each modification. RESULTS: During the study period, 80 devices were implanted (HMII, n = 54; HM3, n = 26). The 8-year incidence of DLI was 15% (n = 8) in HMII patients and 0% in HM3 patients (p = 0.039). DLI was not associated with hospital mortality. The modified dressing protocol and tunneling method was associated with a significantly better DLI incidence rate in comparison to the previous one: Protocol-A (n = 17), Protocol-B (n = 63), 35% vs 3% (p = 0.0009), Method-A (n = 13), Method-B (n = 42), Method-C (n = 25), 46% vs 5% vs 0% (p = 0.0001). The rete of freedom form DLI at 1, 2, and 3 years had also significant difference between groups: Protocol-A and Protocol-B, 80%, 54%, 54% vs 96%, 96%, 96%, respectively (p < 0.0001), Method-A, Method-B and Method-C, 76%, 44%, 44%, vs 94%, 94%, 94% vs 100%, 100%, respectively (p < 0.0001). CONCLUSIONS: A standardized triple driveline tunneling strategy and waterproof dressing protocol reduced driveline infection in HM3 patients to 0%.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Infecções Relacionadas à Prótese , Humanos , Estudos Retrospectivos , Coração Auxiliar/efeitos adversos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/complicações , Incidência , Bandagens/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle
12.
Pain Pract ; 23(3): 277-289, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36478501

RESUMO

BACKGROUND: We investigated the efficacy and safety of twice-daily bilayer sustained-release tramadol hydrochloride tablets (35% immediate-release; 65% sustained-release) in patients with postherpetic neuralgia. METHODS: This was a Phase III treatment-withdrawal study with 1-4-week dose-escalation, 1-week fixed-dose, and 4-week randomized, double-blind, placebo-controlled withdrawal periods performed at 43 medical institutions in Japan. Patients aged ≥20 years, ≥3 months after the onset of herpes zoster with localized, persistent pain despite fixed-dose analgesics for ≥2 weeks before enrollment were eligible. Patients started tramadol at 100 mg/day and its dose escalated to a maximum of 400 mg/day to achieve a reduction in their Numeric Rating Scale (NRS) for pain of ≥2 points. Eligible patients were randomized to continue tramadol or switched to placebo for 4 weeks (double-blind period). Patients were withdrawn due to inadequate analgesia (NRS deteriorated on ≥2 consecutive days) or their request. RESULTS: Overall, 252 patients started tramadol and 173 were randomized (tramadol: 85; placebo: 88). Tramadol was superior to placebo for the primary endpoint (time from randomization to an inadequate analgesic effect) with log-rank test p = 0.0005. The hazard ratio was 0.353 (95% confidence interval 0.190-0.657) in favor of tramadol and fewer patients in the tramadol group experienced inadequate analgesic effects (16.9% vs. 39.8%). Adverse events in ≥10% of patients in the open-label period were constipation (43.8%), nausea (34.9%), somnolence (18.5%), and dizziness (11.6%). The frequencies of adverse events in the double-blind period were similar in both groups. CONCLUSION: Sustained-release tramadol tablets with an immediate-release component are effective and well tolerated for managing postherpetic neuralgia.


Assuntos
Neuralgia Pós-Herpética , Tramadol , Humanos , Neuralgia Pós-Herpética/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Analgésicos/uso terapêutico , Comprimidos/uso terapêutico , Método Duplo-Cego , Analgésicos Opioides/uso terapêutico , Resultado do Tratamento
13.
Circ J ; 87(2): 306-311, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36351594

RESUMO

BACKGROUND: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation. CONCLUSIONS: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana , Humanos , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Deambulação Precoce/efeitos adversos , Resultado do Tratamento , Ponte de Artéria Coronária/métodos , Prognóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Doença da Artéria Coronariana/etiologia , Fatores de Risco
14.
Intern Med ; 61(21): 3189-3196, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36328585

RESUMO

Objective This study examined whether or not the disease control in Japanese patients with systemic lupus erythematosus (SLE) had improved in recent years and its possible association with altered balance between the use of glucocorticoids and immunosuppressants. Methods We enrolled Japanese patients with SLE who visited our medical center during 2013-2017 (Group A, 75 patients) and compared them with patients encountered during 1999-2003 (Group B, 69 patients; not overlapping with Group A). Patient background characteristics, doses of glucocorticoids, and the use of immunosuppressants at the times of SLE onset and disease flares were reviewed from the medical records. Disease flare was defined as new British Isles Lupus Assessment Group 2004 A or B scores in at least one system. Results Lupus nephritis and neuropsychiatric manifestations were less frequently observed in Group A than in Group B (p=0.042 and p=0.045, respectively). Although the initial glucocorticoid dosage was similar between the groups, the inclusion rate of immunosuppressants in the initial SLE treatment was significantly higher in Group A than in Group B (56% vs. 6% in Group B, p<0.001). The median number of SLE flares per person-year was significantly lower in Group A than in Group B (0 vs. 0.3, respectively, p<0.001), and a propensity score-matched analysis indicated the association of SLE flare with the non-use of immunosuppressants in the initial treatment (p=0.012). The rates of infectious diseases and other complications were similar between the groups. Conclusion The recent aggressive use of immunosuppressants in Japan resulted in a reduction in the rate of SLE flare.


Assuntos
Glucocorticoides , Lúpus Eritematoso Sistêmico , Humanos , Glucocorticoides/efeitos adversos , Imunossupressores/efeitos adversos , Japão/epidemiologia , Exacerbação dos Sintomas , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico
15.
Nagoya J Med Sci ; 84(3): 673-677, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36237877

RESUMO

We report the case of a 20-year-old woman with carinal adenoid cystic carcinoma who underwent left sleeve pneumonectomy in the left lateral decubitus position, during which severe desaturation was encountered. After transecting the left main bronchus, the left lung was selectively intubated and ventilated. However, oxygenation was inadequate. Hence, venoarterial extracorporeal membrane oxygenation (ECMO) was introduced. Initially, Barclay's procedure was planned to preserve the left lung, but this plan was altered due to the extent of the tumor and unstable ventilation. After the lesion was removed, the trachea and right main bronchus were anastomosed end-to-end. During left pneumonectomy, the right lung was selectively ventilated, but oxygen saturation (SpO2) dropped to <70% despite ECMO. SpO2 improved on additionally ventilating the left lung using another breathing circuit. Temporary right chest closure was performed with ventilation of the left lung across the thoracotomy wound. The patient was turned to the semi-supine position, and tolerated selective right lung ventilation with ECMO. Subsequently, left thoracotomy and pneumonectomy were successfully performed. Careful management is required for desaturation in left sleeve pneumonectomy in the left lateral decubitus position.


Assuntos
Neoplasias Pulmonares , Pneumonectomia , Adulto , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Toracotomia/métodos , Traqueia/patologia , Traqueia/cirurgia , Adulto Jovem
16.
ACS Med Chem Lett ; 13(10): 1591-1597, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36262388

RESUMO

Fragment-based ligand discovery was successfully applied to histone deacetylase HDAC2. In addition to the anticipated hydroxamic acid- and benzamide-based fragment screening hits, a low affinity (∼1 mM) α-amino-amide zinc binding fragment was identified, as well as fragments binding to other regions of the catalytic site. This alternative zinc-binding fragment was further optimized, guided by the structural information from protein-ligand complex X-ray structures, into a sub-µM, brain penetrant, HDAC2 inhibitor (17) capable of modulating histone acetylation levels in vivo.

17.
Anal Bioanal Chem ; 414(28): 8125-8142, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36181513

RESUMO

In drug metabolism studies in horses, non-targeted analysis by means of liquid chromatography coupled with high-resolution mass spectrometry with data-dependent acquisition (DDA) has recently become increasingly popular for rapid identification of potential biomarkers in post-administration biological samples. However, the most commonly encountered problem is the presence of highly abundant interfering components that co-elute with the target substances, especially if the concentrations of these substances are relatively low. In this study, we evaluated the possibility of expanding DDA coverage for the identification of drug metabolites by applying intelligently generated exclusion lists (ELs) consisting of a set of chemical backgrounds and endogenous substances. Daprodustat was used as a model compound because of its relatively lower administration dose (100 mg) compared to other hypoxia-inducible factor stabilizers and the high demand in the detection sensitivity of its metabolites at the anticipated lower concentrations. It was found that the entire DDA process could efficiently identify both major and minor metabolites (flagged beyond the pre-set DDA threshold) in a single run after applying the ELs to exclude 67.7-99.0% of the interfering peaks, resulting in a much higher chance of triggering DDA to cover the analytes of interest. This approach successfully identified 21 metabolites of daprodustat and then established the metabolic pathway. It was concluded that the use of this generic intelligent "DDA + EL" approach for non-targeted analysis is a powerful tool for the discovery of unknown metabolites, even in complex plasma and urine matrices in the context of doping control.


Assuntos
Doping nos Esportes , Animais , Cromatografia Líquida/métodos , Cavalos , Espectrometria de Massas/métodos , Preparações Farmacêuticas , Detecção do Abuso de Substâncias/métodos
18.
SAGE Open Med Case Rep ; 10: 2050313X221116681, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958880

RESUMO

A 73-year-old man presented with multiple giant coronary artery aneurysms. Twelve years prior to the presentation, he had undergone coronary artery bypass grafting. At that time, he exhibited small aneurysms (16 mm diameter) in the right coronary artery and a single aneurysm (10 mm diameter) in the left circumflex artery. During follow-up, the aneurysms gradually increased in size (to 45 and 30 mm, respectively, at 12 years after surgery). We resected all of the aneurysms and performed coronary artery bypass grafting of the left circumflex artery through re-sternotomy.

19.
Curr Drug Metab ; 23(10): 850-865, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017833

RESUMO

BACKGROUND: Vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, is a substance which carries a lifetime ban in both horse racing and equestrian competition. A comprehensive metabolic study of vadadustat in horses has not been previously reported. OBJECTIVE: Metabolism and elimination profiles of vadadustat in equine plasma and urine were studied for the purpose of doping control. METHODS: A nasoesophageal administration of vadadustat (3 g/day for 3 days) was conducted on three thoroughbred mares. Potential metabolites were comprehensively detected by differential analysis of full-scan mass spectral data obtained from both in vitro studies with liver homogenates and post-administration samples using liquid chromatography high-resolution mass spectrometry. The identities of metabolites were further substantiated by product ion scans. Quantification methods were developed and validated for the establishment of the excretion profiles of the total vadadustat (free and conjugates) in plasma and urine. RESULTS: A total of 23 in vivo and 14 in vitro metabolites (12 in common) were identified after comprehensive analysis. We found that vadadustat was mainly excreted into urine as the parent drug together with some minor conjugated metabolites. The elimination profiles of total vadadustat in post-administration plasma and urine were successfully established by using quantification methods equipped with alkaline hydrolysis for cleavage of conjugates such as methylated vadadustat, vadadustat glucuronide, and vadadustat glucoside. CONCLUSION: Based on our study, for effective control of the misuse or abuse of vadadustat in horses, total vadadustat could successfully be detected for up to two weeks after administration in plasma and urine.


Assuntos
Glicina , Fígado , Cavalos , Animais , Feminino , Espectrometria de Massas , Cromatografia Líquida/métodos , Glicina/metabolismo , Fígado/metabolismo
20.
Acta Med Okayama ; 76(3): 339-342, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35790366

RESUMO

A 90-year-old man presented with muscle weakness, difficulty concentrating, and dysphagia. About eighteen months prior to presentation, lansoprazole had been initiated to prevent stress ulcers; he also had a history of total thyroidectomy due to papillary thyroid cancer ten years prior. Laboratory findings were as follows: K 2.4 mEq/L, Ca 3.7 mg/dL, Mg 1.3 mg/dL, CK 5386 U/L, and intact PTH (iPTH) 14 pg/mL. Rhabdomyolysis with multiple electrolyte imbalances under proton pump inhibitor (PPI) treatment was diagnosed. We initiated intravenous hydration and electrolyte supplementation with discontinuation of PPI. After discontinuing PPI, the patient's serum magnesium, potassium, and calcium levels normalised with oral vitamin D and calcium supplementation. PPIs can cause hypocalcaemia and hypokalaemia via hypomagnesemia; hypocalcaemia is also a common postoperative complication of thyroidectomy. Careful monitoring of electrolyte levels is required in patients with long-term PPI treatment, especially in post-thyroidectomy cases.


Assuntos
Hipocalcemia , Rabdomiólise , Neoplasias da Glândula Tireoide , Idoso de 80 Anos ou mais , Cálcio , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Tireoidectomia/efeitos adversos
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