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1.
Diabetes Obes Metab ; 26(7): 2588-2597, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38618974

RESUMO

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Pessoa de Meia-Idade , Feminino , Idoso , Taxa de Filtração Glomerular/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Glucosídeos/farmacocinética , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/efeitos adversos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Adulto , Nefropatias Diabéticas/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Insuficiência Renal/metabolismo , Transportador 2 de Glucose-Sódio , Glicosúria/induzido quimicamente , Benzofuranos
2.
Surg Endosc ; 38(3): 1512-1522, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38253696

RESUMO

BACKGROUND: The extent of postoperative pain following transoral thyroidectomy is not well-understood and remains a subject of debate. This study aims to analyze and compare postoperative pain levels between patients undergoing transoral and conventional transcervical thyroidectomy. METHODS: A prospective evaluation on postoperative pain was conducted in 310 patients undergoing conventional thyroidectomy and 194 undergoing transoral thyroidectomy. Pain levels were evaluated using the numerical rating scale (NRS, ranging from 0 to 10) through preoperative and postoperative questionnaires at specified time points: 1, 3, and 6 days, and 1 and 3 months following surgery. Propensity score-matched analysis was carried out based on six covariates: sex, age, body mass index, extent of thyroidectomy, tumor size, and central neck dissection. RESULTS: After propensity score matching based on the six covariates, 121 patient pairs were identified from each group. Within this matched cohort, postoperative pain scores significantly worsened 1 day after surgery but showed progressive recovery up to 3 months post-surgery in both groups. The transoral group exhibited higher postoperative pain scores than the conventional group from day 1 (4.43 ± 2.6 vs. 3.11 ± 2.5, p < 0.001) to day 6 (1.76 ± 1.9 vs. 1.13 ± 1.6, p = 0.016) post-surgery, with no significant difference noted at 1 month. Among transoral procedures, pain scores were significantly higher for the endoscopic approach compared to the robotic approach on days 1 (5.52 ± 2.3 vs. 4.29 ± 2.3, p = 0.028) and 3 (3.52 ± 2.5 vs. 2.64 ± 2.0, p = 0.047) post-surgery. CONCLUSIONS: Postoperative pain was significantly higher in transoral thyroidectomy compared to conventional thyroidectomy up to 6 days post-surgery. Within the transoral group, the robotic procedure resulted in lower pain levels than the endoscopic approach during the early postoperative period.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Glândula Tireoide , Humanos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Pontuação de Propensão , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/cirurgia , Esvaziamento Cervical/efeitos adversos , Esvaziamento Cervical/métodos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos
3.
Cureus ; 16(7): e64776, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39156265

RESUMO

Charcot neuroarthropathy (CN) is a chronic degenerative disorder of bones and joints, mostly associated with diabetes mellitus and human immunodeficiency virus. CN of the upper limb is rare, with only 58 case reports identified on PubMed with the majority of cases being closely associated with syringomyelia. Very rarely, cervical spondylotic myelopathy (CSM) is associated with CN of the upper limb; with very few literature reporting this association. This case report presents a rare case of Charcot arthropathy of the shoulder caused by CSM. A 57-year-old female presented to the emergency department following trauma to the right shoulder. On clinical examination, there was evidence of tenderness, extensive swelling, and bruising with a lack of range of motion along with numbness in the right arm and legs. Through radiographic and laboratory investigations, a diagnosis of CN secondary to CSM was made. A reverse total shoulder arthroplasty was performed however, this was complicated at two weeks with an atraumatic glenoid fracture and dislocation. First-stage revision surgery was then performed to allow fracture healing pending second-stage revision surgery. This report provides insight into the very rare possibility of the association of CN of the shoulder with CSM. A review of the literature suggests reverse shoulder arthroplasty is the gold standard for cases of severe bone and soft tissue damage. When undergoing investigations for Charcot neuroarthropathy, physicians must undertake a full detailed history along with a detailed neurological examination and imaging of the cervical spine to not miss the association with CSM.

4.
Chemosphere ; 363: 142806, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38986783

RESUMO

A gas chromatography coupled to high-resolution mass spectrometry (GC-HR/MS) has been used as the standard method for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs), which are regulated at screening and action levels in the environment. However, several alternative methods have been attempted due to the disadvantage of its high cost. Although a gas chromatography with triple quadrupole mass spectrometry (GC-QqQ-MS/MS) has been used in a wide variety of sample matrices, showing that they are interchangeable, there has been a lack of comprehensive studies on statistical agreement with GC-HR/MS. In this study, a pairwise comparison of the total concentrations of PCDDs/Fs in 90 soil field samples obtained by two mass spectrometric methods was performed using the Passing-Bablok (P&B) regression and Bland-Altman (B&A) analysis for the method comparison. According to the result of the B&A analysis, the concentration range of PCDDs/Fs was between 98.2 and 1760 pg/g showed good agreement between two methods at the 95 % confidence level (CL). Although there was a large discrepancy between the two methods in the low concentrations (<16.5 pg/g of PCDDs/Fs), this result was similar to the P&B regression analysis. As the verification results by B&A and P&B regression analysis, the interchangeable concentration range between the two methods was confirmed to be adequate for the monitoring of PCDDs/Fs regulating levels in soils.


Assuntos
Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Dibenzodioxinas Policloradas , Poluentes do Solo , Solo , Dibenzodioxinas Policloradas/análise , Poluentes do Solo/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Monitoramento Ambiental/métodos , Solo/química , Dibenzofuranos Policlorados/análise , Benzofuranos/análise
5.
Transl Clin Pharmacol ; 32(1): 63-72, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586120

RESUMO

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence. Trial Registration: ClinicalTrials.gov Identifier: NCT06147908.

6.
Mar Pollut Bull ; 200: 116160, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377865

RESUMO

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) were assessed in coastal sediments from industrial bays in South Korea to evaluate the pollution levels and their environmental impact. The mean sediment concentrations of Σ17 PCDD/Fs, Σ18 PCBs, and Σ15 PCNs were 198 ± 140, 3427 ± 7037, and 85 ± 336 pg/g dw, respectively. Generally, pollutant concentrations in the inner bay were higher than those in the outer bay, indicating the influence of industrial emissions and harbor activities. The primary sources were identified as steel manufacturing and wastewater treatment plants for PCDD/Fs, harbor and shipbuilding activities for PCBs, and combustion-related sources for PCNs. Notably, PCDD/F concentrations exceeded sediment guideline values. The combined effects of PCDD/Fs and PCBs demonstrated adverse impacts on aquatic organisms. Hence, the release of toxic pollutants into the marine environment could have potential biological effects due to the combined impact of these various compounds.


Assuntos
Dioxinas , Poluentes Ambientais , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análise , Baías , Dibenzofuranos , Naftalenos/análise , República da Coreia , Dibenzofuranos Policlorados , Dioxinas/análise
7.
Food Chem ; 451: 139498, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38703730

RESUMO

Concerns about dioxin-like compounds have increased; however, the monitoring of polychlorinated naphthalenes (PCNs) in food and the assessment of dietary intake remain limited. In this study, various foods were collected from Korean markets and analyzed for PCNs. Fishery products exhibited the highest mean concentration (48.0 pg/g ww) and toxic equivalent (TEQ) (0.0185 pg-TEQ/g ww). Agricultural products were the largest contributors (35.7%) to the total dietary intake of PCNTEQ, followed by livestock products (33.6%), fishery products (20.2%), and processed foods (10.5%). The mean intake of PCNTEQ for the Korean population was 0.901 pg-TEQ/day for males and 0.601 pg-TEQ/day for females. Generally, males and younger groups had higher daily intakes of PCNTEQ, but they did not exceed the tolerable weekly intakes. Nonetheless, it is important to manage potential health risks associated with PCNs and other dioxin-like compounds by identifying major food items contributing to PCN exposure and considering age and gender differences.


Assuntos
Contaminação de Alimentos , Naftalenos , República da Coreia , Humanos , Contaminação de Alimentos/análise , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Naftalenos/análise , Adolescente , Criança , Poluentes Ambientais/análise , Idoso , Pré-Escolar , Exposição Dietética/análise , Animais
8.
Adv Sci (Weinh) ; 11(28): e2401821, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38738755

RESUMO

The demand for gas sensing systems that enable fast and precise gas recognition is growing rapidly. However, substantial challenges arise from the complex fabrication process of sensor arrays, time-consuming data transmission to an external processor, and high energy consumption in multi-stage data processing. In this study, a gas sensing system using on-chip annealing for fast and power-efficient gas detection is proposed. By utilizing a micro-heater embedded in the gas sensor, the sensing material of adjacent sensors in the same substrate can be easily varied without further fabrication steps. The response to oxidizing gas is constrained in metal oxide (MOX) sensing material with small grain sizes, as the depletion width of grain cannot extend beyond the grain size during the gas reaction. On the other hand, the response to reducing gases and humidity, which decrease the depletion width, is less affected by grain sizes. A readout circuit integrating a differential amplifier and dual FET-type gas sensors effectively emphasizes the response to oxidizing gases by canceling the response to reducing gases and humidity. The selective on-chip annealing method is applicable to various MOX sensing materials, demonstrating its potential for application in commercial fields due to its simplicity and expandability.

9.
Clin Ther ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033046

RESUMO

PURPOSE: Gastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis. METHODS: This study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated. FINDINGS: The mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%. IMPLICATIONS: Multiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis. CLINICALTRIALS: gov identifier: NCT04967014.

10.
Neurotherapeutics ; 21(4): e00357, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631990

RESUMO

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

11.
Antioxidants (Basel) ; 13(4)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38671837

RESUMO

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

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