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2.
Chem Asian J ; : e202400828, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231000

RESUMEN

Aqueous zinc-ion batteries (AZIBs) are a potential new technology in energy storage due to their high energy density, affordability, and environmental friendliness. Unchecked zinc dendrite formation during cycling still hinders the development of AZIBs, resulting in an unstable interface, a short cycling life, a considerable capacity decline, and security issues. Herein, we demonstrate a novel nanofiber membrane based on a polyethylenimine-polyacrylonitrile (PEI-PAN) polymer produced by electrospinning with entangled nanofibers for AZIBs applications. The as-fabricated PEI/PAN membrane has a porous structure that is homogeneous, tortuous, and linked, with high porosity and superior electrolyte wettability. The PEI/PAN membrane has good thermal stability at 200 °C and high ionic conductivity of up to 5.3 x 10-4 S cm-1. This membrane provides Zn/Zn symmetric cells with an ultralong cycle life of over 250 hours at 3 mA cm-2. Additionally, MnO2/Zn cells outperforms commercial filter paper in terms of cycle stability and rate performance. This work demonstrates a simple technique for fabricating advanced nanofiber membranes for AZIBs to modify Zn2+ deposition behavior and improve Zn dendrite resistance.

3.
Cureus ; 16(7): e65838, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39219942

RESUMEN

Laxative misuse is a well-known occurrence, most often identified in patients struggling with eating disorders. Polyethylene glycol (PEG) 3350 is a readily available, well-tolerated osmotic laxative. High doses of PEG 3350 may cause gastrointestinal upset, diarrhea, dehydration, and electrolyte imbalance, although systemic toxicity is infrequently reported. This case report highlights the exceedingly rare metabolic derangements associated with profound levels of protracted PEG misuse. A 60-year-old female presented to the emergency department with altered mental status. She was found to have acute renal failure (ARF), anion gap metabolic acidosis (AGMA), and rhabdomyolysis secondary to excessive PEG 3350 use, requiring continuous renal replacement therapy (CRRT). Renal function improved after three days of CRRT, and no alternative causes beyond PEG ingestion were found to account for her mental status changes or metabolic anomalies. This report illustrates the importance of considering osmotic laxative misuse in the setting of pre-renal and intrinsic renal failure.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39242431

RESUMEN

Encapsulating the enzyme in metal-organic frameworks (MOFs) is a convenient method to prepare MOF-enzyme biocomposite. In this study, Candida antarctica lipase B (CAL-B) was chosen to immobilize in Cu-BTC MOF under ultrasound irradiation. CAL-B was immobilized in Cu-BTC under ultrasound at 21 kHz and 11.4 W/cm2 and incubation. 98% of CAL-B was immobilized in Cu-BTC with 99 U/mg activity (threefold more active than the free CAL-B). The prepared biocomposite was characterized using FT-IR, XRD, TGA, SEM, EDX, and BET. The thermal and solvent stability of CAL-B@Cu-BTC was investigated. It was found that at a temperature of 55 â„ƒ, CAL-B@Cu-BTC maintains its activity even after 2 h of incubation. Furthermore, in the presence of 20% and 50% concentrations of MeCN, THF, and DMF, CAL-B@Cu-BTC was found to have an activity of over 80%. A prepared biocatalyst was used to synthesize 1,3,4,5-tetrasubstituted pyrazole derivatives (50-75%) in a one-pot vessel, by adding phenyl hydrazine hydrochlorides, benzaldehydes, and dimethyl acetylenedicarboxylate.

5.
Biol Trace Elem Res ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256330

RESUMEN

Nanomaterials offer several promising prospects in the field of farm animal reproduction, encompassing a broad range of applications such as transgenesis and the precise delivery of substances to sperm cells, antimicrobial, antioxidants properties as well as their potent role in improving cryopreservation methods. The aim of the present study is to explore the effect of supplementing the semen extender with 10 µg/mL nano gold (Au-NPs10), 10 µg/mL nano silver (Ag-NPs10), 1 µg/mL nano selenium (Se-NPs1), and 100 µg/mL nano zinc oxide (ZnO-NPs100) on sperm characteristics and kinematics parameters, acrosome integrity, oxidative biomarkers, morphological and apoptosis-like changes of frozen-thawed buffalo bull sperm, and, ultimately, their fertilizing capacity. The results revealed that all aforementioned nano materials significantly improved viability, progressive motility, membrane integrity, acrosome integrity, and kinematic parameters as well as apoptosis-like changes of post-thawed buffalo bull sperm compared to the control (p < 0.05). No discernible effects were observed on sperm ultrastructure morphology measures as a response to the addition of these metallic nanoparticles to the extender. The values of caspase 3 significantly decreased by 64.22, 45.99, 75.59, and 49.39% in Au-NPs10, Ag-NPs10, Se-NPs1, and ZnO-NPs100 treated groups, respectively, compared to the control. The addition of 100 µg ZnO-NPs to the extender significantly decreased the total count of bacteria, fungi, and yeast compared to the control (p < 0.05). The AuNPs10 and SeNPs1 treated groups showed lower content of malondialdehyde, hydrogen peroxide, and nitric oxide concentrations and higher values of total antioxidant capacity of post-thawed extended semen (p < 0.05). Pregnancy rates increased by 17.5, 20, and 30% in buffalo cows inseminated with sperm treated with ZnO-NPs100, Se-NPs1, and Au-NPs10, respectively, compared to the control group. The present results indicate that the freezing extender supplemented with metallic nanoparticles can be an effective strategy to enhance the cryotolerance and fertility potential of buffalo bull sperm.

6.
RSC Adv ; 14(34): 24503-24515, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39108954

RESUMEN

Cleome amblyocarpa Barr. and Murb. from the family Cleomaceae is used in folk medicine as it has analgesic, anti-inflammatory, antibacterial and antioxidant activities. In this study, ten compounds from the whole plant of C. amblyocarpa, a wild plant that grows in the Sinai Peninsula of Egypt, were isolated. Six compounds, ß-sitosterol 3-O-ß-d-glucoside 2, calycopterin 5, rhamnocitrin 6, 17α-hydroxycabraleahy-droxylactone 7, cleogynol 8, and ß-sitosterol 10 were first isolated from this species. In addition, four previously reported compounds, kaempferol-3, 7-dirhamnoside 1, 15α-acetoxycleomblynol A 3, and 11-α-acetylbrachy-carpone-22(23)-ene 4, as well as cleocarpanol 9, were isolated and identified. Isolated compounds were evaluated to determine their analgesic properties utilizing a hot-plate test method, and their anti-inflammatory effects utilizing rat paw edema. In a hot-plate test, compounds 3, 4, 7, 8, and 9 showed significant pain inhibition in latency time as compared to the normal group. Compounds 3-9 exhibited a significant inhibition of carrageenan-induced inflammation. According to the results of this work, compounds 3 and 4 (Dammarane triterpenoid) have the strongest analgesic/anti-inflammatory activity as compared to the other tested compounds. These results give support to the medicinal benefits of the plant as an analgesic along with an anti-inflammatory agent in traditional therapy. Molecular modelling studies of the isolated compounds 3 and 4 assessed the molecular affinity and binding interaction patterns for these compounds towards COX-2 as compared to specific COX-2 inhibitors and in relation to COX-1 isozyme. Compound 3 revealed extended accommodation across COX-2's hydrophobic sub-pockets and preferential thermodynamic stability across molecular dynamics simulations.

7.
RSC Adv ; 14(34): 24631-24642, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39114437

RESUMEN

This study presents findings on the production and analysis of activated carbon (AC), which exhibits a significantly expansive surface area derived from readily available and inexpensive agroforestry waste, specifically coconut shells. The carbon materials displayed encouraging features for electrochemical energy storage applications with a high specific surface area (2920 m2 g-1), an ordered mesoporous structure (∼2.5 nm), and substantial electronic conductivity. By altering the surface properties of AC materials, they exhibited different energy storage responses while using an ionic liquid as an electrolyte. Electrodes composed of AC sourced from coconut shells demonstrated notably high specific capacitance (78 F g-1) and retained capacitance when assessed within symmetric electrical double-layer capacitors (EDLCs) employing organic electrolytes. Interestingly, the AC cell in an organic electrolyte delivered a specific energy (Es) of 67 W h kg-1 at a specific power (Ps) of 1237 W kg-1 at the current density of 1 A g-1 and still provided Es of 64, 60, 58, 57, and 52 W h kg-1 at Ps of 2477, 3724, 4971, 6218 and 12 480 W kg-1 at the current density of 2, 3, 4, 5 and 10 A g-1. This work demonstrates the effect of different pore volumes on the electrocatalytic activity of AC derived from natural product waste. Our results indicate the feasibility of employing these electrodes for lab-scale applications. Thus, the AC material emerges as a highly promising substance, poised to advance the creation of cost-efficient, environmentally sustainable, high-performance, high-power devices.

8.
Front Med (Lausanne) ; 11: 1399305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114823

RESUMEN

Introduction: Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects children. Aim: To investigate whether hydrocortisone or tacrolimus could be more effective for treating AD in children. Patients and methods: This clinical randomized investigation included 100 children with AD who met the eligibility criteria. AD patients were recruited from Tanta University's Dermatology Department and divided into two groups (n = 50)., For four months, group 1 (the hydrocortisone group) received topical hydrocortisone cream. Group 2 received topical tacrolimus for four months. A dermatologist evaluated the patients at the start and four months after the treatment had been initiated to measure serum concentrations of neutrophil chemoattractant growth-related oncogene-α (GRO-α), interferon gamma induced protein 10 (IP-10), tumor necrosis factor alpha (TNF-α), vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1). All patients were examined using the modified Eczema Area and Severity Index (mEASI) score. Results: Tacrolimus group showed a significant reduction in serum levels of all measured biomarkers (p < 0.05) when compared to its baseline and when compared to the hydrocortisone group. Both groups displayed a significant decline in mEASI score in comparison with their baseline values (p < 0.05). Conclusion: In children with AD, tacrolimus reduces inflammatory biomarkers better than hydrocortisone, suggesting its potential as a more effective treatment option. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05607901.

9.
Inflammopharmacology ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192162

RESUMEN

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that lasts a long time and has a variety of causes. AIM: The primary aim of this study was to evaluate pentoxifylline's (PTX) essential function in patients with UC. METHODS: Fifty-two mild to moderate UC patients who matched the eligibility requirements participated in this clinical study. One gram of mesalamine (t.i.d.) and a placebo were administered to the mesalamine group (n = 26) for a duration of 24 weeks. Mesalamine 1 g t.i.d. and PTX 400 mg two times daily were administered to the PTX group (n = 26) for 24 weeks. A gastroenterologist investigated patients at the start and 6 months after the medication was given to assess disease activity index (DAI) and numeric pain rating scale (NRS). Also, interleukin-6 (IL-6), sphingosine 1 phosphate (S1P), tumor necrosis factor-alpha (TNF-α), and fecal myeloperoxidase (MPO) were measured before and after therapy. Zonula occuldin-1 (ZO-1) and signal transducer and activator of transcription factor-3 (STAT-3) expression was assessed before and after therapy as well as histological assessment. Short Form 36 Health Survey (SF-36), was assessed for each patient before and after 6 months of treatment. RESULTS: The PTX group showed statistically lower levels of serum SIP, TNF-α, IL-6, faecal MPO, gene expression of STAT-3, and a significant increase of ZO-1 in comparison with the mesalamine group. DAI and NRS significantly decreased whereas SF-36 significantly increased in the PTX group. CONCLUSION: PTX could alleviate inflammation in patients with UC, so it might be promising adjunctive for patients with UC. TRIAL REGISTRATION IDENTIFIER: NCT05558761.

10.
Front Pharmacol ; 15: 1434512, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156113

RESUMEN

Background: Parkinson's disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and bradykinesia. PD patients' brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials. Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory. Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs. Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 [95% CI (0.8-0.97), p = 0.01], 0.73 [95% CI (0.53-1), p = 0.05] and 0.85 [95% CI (0.75-0.97), p = 0.01]. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant. Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD.

11.
Neurotox Res ; 42(5): 38, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177895

RESUMEN

Melatonin (MTN) is a neuro-hormone released from the pineal gland. MTN secretion is regulated by different neuronal circuits, including the retinohypothalamic tract and suprachiasmatic nucleus (SCN), which are affected by light. MTN is neuroprotective in various neurodegenerative diseases, including Parkinson's disease (PD). MTN circulating level is highly blunted in PD. However, the underlying causes were not fully clarified. Thus, the present review aims to discuss the potential causes of blunted MTN levels in PD. Distortion of MTN circadian rhythmicity in PD patients causies extreme daytime sleepiness. The underlying mechanism for blunted MTN response may be due to reduction for light exposure, impairment of retinal light transmission, degeneration of circadian pacemaker and dysautonomia. In conclusion, degeneration of SCN and associated neurodegeneration together with neuroinflammation and activation of NF-κB and NLRP3 inflammasome, induce dysregulation of MTN secretion. Therefore, low serum MTN level reflects PD severity and could be potential biomarkers. Preclinical and clinical studies are suggested to clarify the underlying causes of low MTN in PD.


Asunto(s)
Ritmo Circadiano , Melatonina , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/sangre , Melatonina/sangre , Melatonina/metabolismo , Ritmo Circadiano/fisiología , Animales , Núcleo Supraquiasmático/metabolismo
12.
Inflammopharmacology ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141151

RESUMEN

Endothelial dysfunction is considered one of the main causes of atherosclerosis and elevated blood pressure. Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatment toward endothelial dysfunction is vinpocetine (VPN). VPN is an ethyl apovincaminate used in the management of different cerebrovascular disorders and endothelial dysfunction through inhibition of atherosclerosis formation. VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE1) as well it has anti-inflammatory and antioxidant effects through inhibition of the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present narrative review was to clarify the mechanistic role of VPN in AS. Most of pro-inflammatory cytokines released from macrophages are inhibited by the action of VPN via NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by inhibiting the expression of pro-inflammatory cytokines. As well, VPN is effective in reducing oxidative stress, a cornerstone in the pathogenesis of AS, through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevent erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress with plaque stability effects could be effective agent in the management of endothelial dysfunction through inhibition of atherosclerosis mediators.

13.
Sci Rep ; 14(1): 18647, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134582

RESUMEN

This article investigates the behavior of hybrid FRP Concrete-Steel columns with an elliptical cross section. The investigation was carried out by gathering information through literature and conducting a parametric study, which resulted in 116 data points. Moreover, multiple machine learning predictive models were developed to accurately estimate the confined ultimate strain and the ultimate load of confined concrete at the rupture of FRP tube. Decision Tree (DT), Random Forest (RF), Adaptive Boosting (ADAB), Categorical Boosting (CATB), and eXtreme Gradient Boosting (XGB) machine learning techniques were utilized for the proposed models. Finally, these models were visually and quantitatively verified and evaluated. It was concluded that the CATB and XGB are standout models, offering high accuracy and strong generalization capabilities. The CATB model is slightly superior due to its consistently lower error rates during testing, indicating it is the best model for this dataset when considering both accuracy and robustness against overfitting.

14.
Immun Inflamm Dis ; 12(8): e1346, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39092773

RESUMEN

BACKGROUND: Atherosclerosis (AS) is a progressive disease that interferes with blood flow, leading to cardiovascular complications such as hypertension, ischemic heart disease, ischemic stroke, and vascular ischemia. The progression of AS is correlated with inflammation, oxidative stress, and endothelial dysfunction. Various signaling pathways, like nuclear erythroid-related factor 2 (Nrf2) and Kruppel-like factor 2 (KLF2), are involved in the pathogenesis of AS. Nrf2 and KLF2 have anti-inflammatory and antioxidant properties. Thus, activation of these pathways may reduce the development of AS. Metformin, an insulin-sensitizing drug used in the management of type 2 diabetes mellitus (T2DM), increases the expression of Nrf2 and KLF2. AS is a common long-term macrovascular complication of T2DM. Thus, metformin, through its pleiotropic anti-inflammatory effect, may attenuate the development and progression of AS. AIMS: Therefore, this review aims to investigate the possible role of metformin in AS concerning its effect on Nrf2 and KLF2 and inhibition of reactive oxygen species (ROS) formation. In addition to its antidiabetic effect, metformin can reduce cardiovascular morbidities and mortalities compared to other antidiabetic agents, even with similar blood glucose control by the Nrf2/KLF2 pathway activation. CONCLUSION: In conclusion, metformin is an effective therapeutic strategy against the development and progression of AS, mainly through activation of the KLF2/Nrf2 axis.


Asunto(s)
Aterosclerosis , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Factores de Transcripción de Tipo Kruppel , Metformina , Factor 2 Relacionado con NF-E2 , Metformina/uso terapéutico , Metformina/farmacología , Humanos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Factores de Transcripción de Tipo Kruppel/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Animales , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
15.
Sci Rep ; 14(1): 18501, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122828

RESUMEN

Terahertz (THz) wireless communication is a promising technology that will enable ultra-high data rates, and very low latency for future wireless communications. Intelligent Reconfigurable Surfaces (IRS) aiding Unmanned Aerial Vehicle (UAV) are two essential technologies that play a pivotal role in balancing the demands of Sixth-Generation (6G) wireless networks. In practical scenarios, mission completion time and energy consumption serve as crucial benchmarks for assessing the efficiency of UAV-IRS enabled THz communication. Achieving swift mission completion requires UAV-IRS to fly at maximum speed above the ground users it serves. However, this results in higher energy consumption. To address the challenge, this paper studies UAV-IRS trajectory planning problems in THz networks. The problem is formulated as an optimization problem aiming to minimize UAVs-IRS mission completion time by optimizing the UAV-IRS trajectory, considering the energy consumption constraint for UAVs-IRS. The proposed optimization algorithm, with low complexity, is well-suited for applications in THz communication networks. This problem is a non-convex, optimization problem that is NP-hard and presents challenges for conventional optimization techniques. To overcome this, we proposed a Deep Q-Network (DQN) reinforcement learning algorithm to enhance performance. Simulation results show that our proposed algorithm achieves performance compared to benchmark schemes.

16.
Plant Physiol Biochem ; 215: 109068, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39216160

RESUMEN

Although much interest has been focused on the role of selenium (Se) in plant nutrition over the last 20 years, the influences of organic selenium (selenomethionine; Se-Met) and inorganic selenium (potassium selenite; Se-K) on the growth and physiological characters of cadmium (Cd)-stressed Glycine max L.) seedlings have not yet been studied. In this study, the impacts of Se-Met or Se-K on the growth, water physiological parameters (gaseous exchange and leaf water content), photosynthetic and antioxidant capacities, and hormonal balance of G. max seedlings grown under 1.0 mM Cd stress were studied. The results showed that 30 µM Se-K up-regulates water physiological parameters, photosynthetic indices, antioxidant systems, enzymatic gene expression, total antioxidant activity (TAA), and hormonal balance. In addition, it down-regulates levels of reactive oxygen species (ROS; superoxide free radicals and hydrogen peroxide), oxidative damage (malondialdehyde content as an indicator of lipid peroxidation and electrolyte leakage), Cd translocation factor, and Cd content of Cd-stressed G. max seedlings. These positive findings were in favor of seedling growth and development under Cd stress. However, 50 µM Se-Met was more efficient than 30 µM Se-K in promoting the above-mentioned parameters of Cd-stressed G. max seedlings. From the current results, we conclude Se-Met could represent a promising strategy to contribute to the development and sustainability of crop production on soils contaminated with Cd at a concentration of up to 1.0 mM. However, further work is warranted to better understand the precise mechanisms of Se-Met action under Cd stress conditions.


Asunto(s)
Antioxidantes , Cadmio , Glycine max , Selenio , Cadmio/toxicidad , Cadmio/metabolismo , Glycine max/efectos de los fármacos , Glycine max/metabolismo , Glycine max/genética , Glycine max/crecimiento & desarrollo , Antioxidantes/metabolismo , Selenio/metabolismo , Selenio/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/metabolismo , Plantones/genética , Plantones/crecimiento & desarrollo , Regulación hacia Abajo/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Selenometionina/metabolismo , Selenometionina/farmacología , Estrés Oxidativo/efectos de los fármacos , Malondialdehído/metabolismo
17.
Eur J Radiol ; 179: 111669, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39137605

RESUMEN

PURPOSE: This retrospective study evaluates the value of 68Ga-DOTATATE PET/CT in the diagnosis and localization of insulinomas, whether sporadic, malignant or MEN-1 associated insulinoma. METHOD: The study included 43 patients, having clinical (symptomatic hypoglycemia) and/or laboratory suspicion of having insulinoma (72 h fasting test with serum insulin ≥18 pmol/L), with available pre-operative 68Ga-DOTATATE PET/CT and CE-CT, and diagnosed with insulinoma confirmed by post-operative histopathology. Preoperative imaging was retrospectively analyzed by two radiologists who were blinded to the final diagnosis and to the results of other imaging modalities. Histopathology of specimen was considered the reference standard, and head-to-head comparison of preoperative CE-CT and PET imaging findings. Findings were classified as true positive (TP), true negative (TN), false positive (FP), and false negative (FN) for each modality. Based on these results, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CE-CT, and 68Ga-DOTATATE PET/CT for the detection of insulinoma were calculated. RESULTS: 43 patients (N = 43 patients, L = 56 lesions), out of these, 37 patients had benign sporadic insulinoma (N = 37, L = 42), only 3 patients had malignant sporadic insulinoma (N = 2, L = 9), and 3 patients had MEN-1 syndrome associated insulinoma (N = 3, L = 5). There was no significant statistical difference in sensitivity (P = 0.3058) and PPV (P = 0.5533) for insulinoma localization in the overall cohort with 68Ga-DOTATATE PET/CT (87.5 %, 90.74 %) compared to CE-CT (80.36 %, 93.75 %). CONCLUSION: 68Ga-DOTATATE PET/CT is a non-invasive imaging modality that can identify most insulinomas. Still, it offers limited additional information when the tumor is localized by other anatomic imaging studies, so should be used as an adjunct when imaging studies fail to localize the tumor in insulinoma patients, especially when minimally invasive surgical is intended.


Asunto(s)
Insulinoma , Compuestos Organometálicos , Neoplasias Pancreáticas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Sensibilidad y Especificidad , Humanos , Insulinoma/diagnóstico por imagen , Femenino , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Adulto , Estudios Retrospectivos , Anciano , Reproducibilidad de los Resultados
18.
Anal Chem ; 96(32): 13166-13173, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39092810

RESUMEN

For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.


Asunto(s)
Bencimidazoles , Compuestos de Bifenilo , Losartán , Telmisartán , Tetrazoles , Valsartán , Bencimidazoles/química , Bencimidazoles/análisis , Tetrazoles/química , Telmisartán/química , Valsartán/química , Losartán/química , Losartán/análisis , Compuestos de Bifenilo/química , Irbesartán/química , Irbesartán/análisis , Imidazoles/química , Benzoatos/química , Valina/química , Valina/análisis , Solventes/química , Estabilidad de Medicamentos
19.
Eur J Med Chem ; 276: 116685, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39042991

RESUMEN

Pseudomonas aeruginosa causes life-threatening infections especially in hospitalized patients and shows an increasing resistance to established antibiotics. A process known as quorum sensing (QS) enables the pathogen to collectively adapt to various environmental conditions. Disrupting this cell-to-cell communication machinery by small-molecular entities leads to a blockade of bacterial pathogenicity. We aim to devise QS inhibitors acting on the PA-specific PQS QS system via the signal-molecule receptor and transcriptional regulator PqsR (MvfR). In this manuscript, we describe the further optimization of PqsR inverse agonists by broadening the structural space of a previously described triazole-bearing lead compound and arriving at highly potent thiazole derivatives with activities against P. aeruginosa virulence factor pyocyanin in the nanomolar range. All new derivatives were profiled regarding biological activity as well as in vitro ADMET parameters. Additionally, we assessed safety-pharmacology characteristics of the two most promising compounds both bearing a 3-chloro-4-isopropoxyphenyl motive. Demonstrating an overall favorable profile, our new PqsR inverse agonists represent a valuable addition as optimized lead compounds, enabling preclinical development of P. aeruginosa-specific pathoblockers.


Asunto(s)
Antibacterianos , Pseudomonas aeruginosa , Percepción de Quorum , Tiazoles , Percepción de Quorum/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Tiazoles/química , Tiazoles/farmacología , Tiazoles/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Relación Estructura-Actividad , Humanos , Descubrimiento de Drogas , Estructura Molecular , Pruebas de Sensibilidad Microbiana , Relación Dosis-Respuesta a Droga , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Animales
20.
Sci Rep ; 14(1): 16694, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030283

RESUMEN

Concrete compressive strength (CS) is a crucial performance parameter in concrete structure design. Reliable strength prediction reduces costs and time in design and prevents material waste from extensive mixture trials. Machine learning techniques solve structural engineering challenges such as CS prediction. This study used Machine Learning (ML) models to enhance the prediction of CS, analyzing 1030 experimental CS data ranging from 2.33 to 82.60 MPa from previous research databases. The ML models included both non-ensemble and ensemble types. The non-ensemble models were regression-based, evolutionary, neural network, and fuzzy-inference-system. Meanwhile, the ensemble models consisted of adaptive boosting, random forest, and gradient boosting. There were eight input parameters: cement, blast-furnace-slag, aggregates (coarse and fine), fly ash, water, superplasticizer, and curing days, with the CS as the output. Comprehensive performance evaluations include visual and quantitative methods and k-fold cross-validation to assess the study's reliability and accuracy. A sensitivity analysis using Shapley-Additive-exPlanations (SHAP) was conducted to understand better how each input variable affects CS. The findings showed that the Categorical-Gradient-Boosting (CatBoost) model was the most accurate prediction during the testing stage. It had the highest determination-coefficient (R2) of 0.966 and the lowest Root-Mean-Square-Error (RMSE) of 3.06 MPa. The SHAP analysis showed that the age of the concrete was the most critical factor in the predictive accuracy. Finally, a Graphical User Interface (GUI) was offered for designers to predict concrete CS quickly and economically instead of costly computational or experimental tests.

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