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1.
Cureus ; 16(6): e61508, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957247

RESUMO

Sleep duration has been proposed as a potential and important modifiable risk factor, yet its precise relationship with hypertension among Asian adults remains unclear. This meta-analysis aims to elucidate the impact of short sleep duration on hypertension risk within the adult Asian population. A systematic search of databases, including PubMed, Scopus, and ScienceDirect, was conducted to identify relevant studies published up to January 4, 2024. Eligible studies comprised observational cohort studies and cross-sectional studies that compared short sleep duration to normal sleep duration in relation to hypertension risk among Asian adults. The definitions for short and normal sleep durations were derived from the respective studies. The random effects model was utilized to pool effect estimates, and all statistical analyses were conducted using Review Manager 5.4 software (RevMan) (Cochrane Collaboration, Oxford, UK). Results from a systematic search obtained seven studies assessing sleep duration and hypertension risk in Asian populations. Based on a meta-analysis of six studies, short sleep duration is associated with a higher hypertension risk when compared to normal sleep duration (OR: 1.36; 95% CI: 1.13-1.64; p: 0.0010; I2: 75%). Subgroup analysis based on sex showed that the association is evident across males (OR: 1.12; 95% CI: 1.01-1.25; p: 0.03; I2: 64%) and females (OR: 1.22; 95% CI: 1.10-1.35; p: 0.0003; I2: 82%). In conclusion, based on the analyzed studies, short sleep duration is associated with a higher mild risk of hypertension, irrespective of sex. Thus, short sleep duration can be a modifiable risk factor that can be prevented to reduce the risk of hypertension. By incorporating sleep hygiene practices and promoting healthy sleep habits, significant improvement in cardiovascular health can be made, especially in hypertension risk at a population level. Further studies on the effect of sleep duration in different age populations should be conducted to confirm the impact of short sleep duration.

2.
PNAS Nexus ; 3(7): pgae271, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39010939

RESUMO

Aflatoxins (AFs) are carcinogenic fungal toxins contaminating up to 25% of the global food supply. Over half of the world's population is exposed to unmonitored levels of AFs, mostly aflatoxin B1 (AFB1). Despite numerous efforts over the past 60 years, there are no solutions to remove AFs safely from food. Here, we present a safe and effective AF-degrading product called "D-Tox", a filtered culture broth of Aspergillus oryzae grown in a food-grade liquid medium. When 5 ppm of AFB1 is added to D-Tox, ∼90% is degraded at 48 and 24 hr at room temperature and 50°C, respectively. Moreover, when varying amounts (0.1 ppm ∼ 100 ppm) of AFB1 are added to D-Tox at 100°C, over 95% of AFB1 is degraded in 1 hr, suggesting a nonenzymatic process. Examining degradation of 100 ppm AFB1 reveals that aflatoxin D1 (AFD1) is the major transient degradant of AFB1, indicating that degradation occurs irreversibly by lactone ring hydrolysis followed by decarboxylation. D-Tox further degrades AFD1 to unknown fragmented products. Importantly, the practical application of D-Tox is also demonstrated, as more than 70% of AFB1 is degraded when wheat, corn, and peanuts naturally contaminated with high levels of AFB1 (0.3 ∼ 4.5 ppm) are boiled in D-Tox for 1 hr. Additionally, D-Tox can degrade other lactone-ring containing mycotoxins, including patulin and ochratoxin. D-Tox exhibits no cytotoxicity under the conditions tested in MCF-7 breast cancer cell lines. In summary, D-Tox is a safe and effective AF-detoxifying product that can enhance global food safety.

3.
OTO Open ; 8(3): e161, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974173

RESUMO

Objective: To use pharyngeal pressure recordings to distinguish different upper airway collapse patterns in obstructive sleep apnea (OSA) patients, and to assess whether these pressure recordings correlate with candidacy assessment for hypoglossal nerve stimulator (HGNS) implantation. Study Design: Prospective case series. Setting: Single tertiary-quaternary care academic center. Methods: Subjects with OSA prospectively underwent simultaneous drug-induced sleep endoscopy (DISE) and transnasal pharyngeal pressure recording with a pressure-transducing catheter. Pressure was recorded in the nasopharynx and oropharynx, and endoscopic collapse patterns were classified based on site, extent, and direction of collapse. Pressure recordings were classified categorically by waveform shape as well as numerically by inspiratory and expiratory amplitudes and slopes. Waveform shape, amplitude, and slope were then compared with the endoscopic findings. Results: Twenty-five subjects with OSA were included. Nasopharyngeal waveform shape was associated with the extent of collapse at the level of the palate (P = .001). Oropharyngeal waveform shape was associated with anatomical site of collapse (P < .001) and direction of collapse (P = .019) below the level of the palate. Pressure amplitudes and slopes were also associated with the extent of collapse at various sites. Waveform shape was also associated with favorable collapse pattern on endoscopy for HGNS implantation (P = .043), as well as surgical candidacy for HGNS (P = .004). Conclusion: Characteristic pharyngeal pressure waveforms are associated with different airway collapse patterns. Pharyngeal pressure is a promising adjunct to DISE in the sleep surgery candidacy evaluation.

4.
Front Cell Infect Microbiol ; 14: 1367566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983114

RESUMO

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.


Assuntos
Encéfalo , Modelos Animais de Doenças , Microglia , Linfócitos T , Animais , Microglia/imunologia , Humanos , Camundongos , Encéfalo/imunologia , Linfócitos T/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia
5.
Bioorg Chem ; 147: 107397, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691905

RESUMO

Phenolics, abundant in plants, constitute a significant portion of phytoconstituents consumed in the human diet. The phytochemical screening of the aerial parts of Centaurium spicatum led to the isolation of five phenolics. The anti-tyrosinase activities of the isolated compounds were assessed through a combination of in vitro experiments and multiple in silico approaches. Docking and molecular dynamics (MD) simulation techniques were utilized to figure out the binding interactions of the isolated phytochemicals with tyrosinase. The findings from molecular docking analysis revealed that the isolated phenolics were able to bind effectively to tyrosinase and potentially inhibit substrate binding, consequently diminishing the catalytic activity of tyrosinase. Among isolated compounds, cichoric acid displayed the lowest binding energy and the highest extent of polar interactions with the target enzyme. Analysis of MD simulation trajectories indicated that equilibrium was reached within 30 ns for all complexes of tyrosinase with the isolated phenolics. Among the five ligands studied, cichoric acid exhibited the lowest interaction energies, rendering its complex with tyrosinase the most stable. Considering these collective findings, cichoric acid emerges as a promising candidate for the design and development of a potential tyrosinase inhibitor. Furthermore, the in vitro anti-tyrosinase activity assay unveiled significant variations among the isolated compounds. Notably, cichoric acid exhibited the most potent inhibitory effect, as evidenced by the lowest IC50 value (7.92 ± 1.32 µg/ml), followed by isorhamnetin and gentiopicrin. In contrast, sinapic acid demonstrated the least inhibitory activity against tyrosinase, with the highest IC50 value. Moreover, cichoric acid exhibited a mixed inhibition mode against the hydrolysis of l-DOPA catalyzed by tyrosinase, with Ki value of 1.64. Remarkably, these experimental findings align well with the outcomes of docking and MD simulations, underscoring the consistency and reliability of our computational predictions with the actual inhibitory potential observed in vitro.


Assuntos
Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Fenóis , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Fenóis/química , Fenóis/farmacologia , Fenóis/isolamento & purificação , Estrutura Molecular , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Simulação de Dinâmica Molecular , Agaricales/enzimologia
6.
Sleep Med ; 119: 267-275, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710132

RESUMO

Sleep is essential for athletes' physical performance as well as their general health, well-being, and quality of life. To assess athletes' sleep behaviors, the Athlete Sleep Behavior Questionnaire (ASBQ) was developed in the English language. However, a validated Arabic-version of the ASBQ is lacking. This study aimed to translate the ASBQ into Arabic (ASBQ-AR) and evaluate its reliability and validity among Arabic-speaking athletes. A total of 458 participants (254 athletes, 202 non-athletes) from four Arabic countries completed the ASBQ-AR and the Insomnia Severity Index (ISI) questionnaires. The psychometric properties of the ASBQ-AR were examined using unidimensional reliability analysis, confirmatory factor analysis (CFA), Item Response Theory (IRT), and convergent validity. The ASBQ-AR had acceptable internal consistency (Cronbach's α = 0.723, McDonald's ω = 0.725) and a factorial structure, confirming its construct validity. CFA demonstrated improved model fit indices after the removal of two potentially misfitting items (items 4 and 13); however, the model's fit to the data remains suboptimal. IRT results indicated that the majority of items demonstrated a good model fit, suggesting effective measurement of the intended construct without significant interference, except for ASBQ-AR 4. Additionally, ASBQ-AR 4 appears to present the highest level of difficulty for respondents. In terms of convergent validity, the mean ASBQ-AR global score was correlated with the mean ISI global score (r = 0.5, p < 0.0001). The ASBQ-AR is a reliable and valid tool for assessing maladaptive sleep practices among Arabic-speaking athletes. Additional refinements to the ASBQ-AR are warranted to optimize its psychometric properties.


Assuntos
Atletas , Psicometria , Sono , Humanos , Masculino , Reprodutibilidade dos Testes , Feminino , Inquéritos e Questionários/normas , Psicometria/normas , Adulto , Sono/fisiologia , Adulto Jovem , Traduções , Tradução , Análise Fatorial
7.
Cureus ; 16(3): e56926, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665701

RESUMO

Coronary artery disease (CAD) poses a global health challenge, necessitating effective preventive strategies. Despite the pivotal role of physical activity in cardiovascular health, many fall short of recommended guidelines for daily physical activity. Simple and accessible, walking presents an opportunity, with increased pace emerging as a potential strategy for reducing the risk of cardiovascular diseases. Thus, we aimed to elucidate the potential association between walking pace and the risk of CAD events in adults without a prior history of CAD through a systematic review. We searched PubMed, Scopus, Web of Science, and ScienceDirect without publication date restrictions to identify prospective cohorts that analyzed walking pace and adult CAD events. The literature search conducted from April 02, 2023, to August 21, 2023, identified a total of four studies (six cohorts) for meta-analysis using random-effects models. The Newcastle-Ottawa Scale was used to assess study quality, and data extraction involved two independent reviewers. The analysis calculated overall relative risks (RRs) and 95% confidence intervals (CIs) for those with the quickest walking paces compared to those with the slowest walking paces. A funnel plot analysis for publication bias and subgroup analysis were also conducted. Results from the meta-analysis involving 160,519 participants and 3,351 CAD events demonstrated a 46% decreased risk for those walking at the quickest pace (pooled RR = 0.54, 95% CI = 0.45-0.66). No significant heterogeneity was observed. In conclusion, walking pace emerges as a significant risk factor for CAD events in adults without a prior history of CAD. It serves as a potential screening tool to identify individuals at higher risk. Promoting a faster walking pace as a daily activity may effectively mitigate the burden of CAD.

8.
Cureus ; 16(3): e56989, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665705

RESUMO

INTRODUCTION: The mental health impact on relatives of cancer patients frequently goes unnoticed and is commonly undervalued. This study aimed to explore how personal factors such as the patient's degree of kin, marital status, cancer stage, and number of diagnosed family members are correlated with the severity of depression and anxiety among relatives of cancer patients. METHOD: This self-administered cross-sectional survey was conducted in Kuwait, employing a random sampling method to recruit participants. Depression and anxiety symptoms were assessed using the validated Arabic versions of the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) scale. RESULTS: The mean age of the relatives of the cancer patients was 38.36 years (±13.44), with a female majority (59.72%). The prevalence of depression in the examined population was 60.1%, with the majority having mild depression (39.3%). On the other hand, the prevalence of anxiety in the same group was 51.2%, with the majority having mild disease (27.5%). Being female and having a cancer patient relative in the metastasis stage put patients' relatives at a greater risk of depression and anxiety. CONCLUSION: The diagnosis of cancer necessitates mental health screenings for patients' relatives, as findings from our study indicate that these individuals are at a high risk of developing depression and anxiety. Targeted support and referrals to specialists are crucial for mitigating the impact on their well-being.

9.
Drug Dev Res ; 85(2): e22166, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38424708

RESUMO

Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti-inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer-407 (P-407). Rats were pretreated with BBR (25 and 50 mg/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P-407 (500 mg/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P-407-adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low-density lipoprotein receptor (LDL-R) and ATP-binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL-R, and ABCA1, and suppressed HMG-CoA reductase in P-407-administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro-inflammatory mediators (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, interferon-γ, IL-4 and IL-18) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) as well as NO and TNF-α release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR toward LPL, HMG-CoA reductase, LDL-R, PSK9, ABCA1, and E-NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E-NTPDase and E-ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation.


Assuntos
Berberina , Hiperlipidemias , Ratos , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/patologia , Estresse Oxidativo , Interleucina-6/metabolismo , Antioxidantes/uso terapêutico , Linfócitos/metabolismo , Linfócitos/patologia , Fator de Necrose Tumoral alfa/metabolismo , Oxirredutases/metabolismo , Oxirredutases/farmacologia , Oxirredutases/uso terapêutico
10.
Cureus ; 16(2): e54553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38516489

RESUMO

Introduction The experience of pain is a complex phenomenon. A patient in the acute postsurgical pain setting may feel a constant bombardment of nociceptive input from the surgical site; this in turn influences psychological factors that determine the overall emotional experience of pain, which is significant. The aim of our study was to investigate the severity of pain in postsurgical patients three days after surgery using the 100 mm visual analog scale (VAS). Methods This was a cross-sectional assessment of postoperative pain. Participants were patients between 18 and 64 years of age who had undergone a surgical procedure (laparoscopic or open surgery), three days prior to the data collection and who were admitted or discharged postoperatively at the Al Salmaniya Complex, Manama, Bahrain. Participants were asked demographic questions about whether they had laparoscopic or open surgeries and completed self-reporting scales. Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for both the presence and severity of depression; Generalized Anxiety Disorder 7-item (GAD-7) was administered to screen for anxiety; the Insomnia Severity Index (ISI) was used to evaluate insomnia; and the VAS was used to evaluate pain.  Results Sixty-seven patients were recruited, with a mean age of 61.53 years (SD = 7.37). Twenty-nine (43%) were females, 38 (57%) were males, 36 (54%) underwent elective surgery, 31 (46%) underwent emergency surgery, 31 (46%) underwent laparoscopic surgery, and 36 (54%) underwent open surgery. The average score on the Brief Pain Inventory Short Form (BPISF) was 8.12 (SD = 1.16), indicating a moderate level of pain. Twenty-six (43%) patients had moderate-severe insomnia, 21 participants (31%) had no insomnia, 17 participants (25%) had subthreshold insomnia, 28 (42%) had moderate depression, five (7%) had moderate-severe depression, and 34 (51%) had severe depression. Eighteen participants (27%) had mild anxiety, 46 (69%) had moderate anxiety, and 3 (4%) had severe anxiety. Six of the participants (9%) reported moderate pain, while 61 participants (91%) reported severe pain.

11.
PLoS One ; 19(3): e0293616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527091

RESUMO

To properly control the network of the power system and ensure its protection, Phasor measurement units (PMUs) must be used to monitor the network's operation. PMUs can provide synchronized real-time measurements. These measurements can be used for state estimation, fault detection and diagnosis, and other grid control applications. Conventional state estimation methods use weighting factors to balance the different types of measurements, and zero injection measurements can lead to large weighting factors that can introduce computational errors. The offered methods are designed to ensure that these zero injection criteria can be strictly satisfied while calculating the voltage profile and observability of the various distribution networks without sacrificing computing efficiency. The proposed method's viability is assessed using standard IEEE distribution networks. MATLAB coding is used to simulate the case analyses. Overall, the study provides a valuable contribution to the field of power distribution system monitoring and control by simplifying the process of determining the optimal locations for PMUs in a distribution network and assessing the impact of ZI buses on the voltage profile of the system.


Assuntos
Sistemas Computacionais , Tecnologia , Injeções
12.
J Allergy Clin Immunol Glob ; 3(2): 100229, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38510797

RESUMO

Background: The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood. Objective: We sought to assess differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic:polycytidylic acid (poly(I:C)) and also to examine whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression. Methods: Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis. Primary human small airway epithelial cells were treated with poly(I:C)-treated neutrophil culture supernatants and were analyzed for type 1 interferon gene expression with a targeted array. Symptoms and exacerbations were assessed in participants over 12 months. Results: A total of 436 genes were differently expressed in neutrophils from children with versus without aeroallergen sensitization at baseline, with significant downregulation of type 1 interferons. These type 1 interferons were significantly upregulated in sensitized children after poly(I:C) stimulation. Confirmatory experiments demonstrated similar upregulation of type 1 interferons in IL-4-treated neutrophils stimulated with poly(I:C). Poly(I:C)-treated neutrophil supernatants from children with aeroallergen sensitization also induced a type 1 interferon response in epithelial cells. Children with aeroallergen sensitization also had higher symptom scores during exacerbations, and these symptom differences persisted for 3 days after prednisolone treatment. Conclusions: Type 1 interferon responses are dysregulated in preschool children with aeroallergen sensitization, which is in turn associated with exacerbation severity. Given the importance of type 1 interferon signaling in viral resolution, additional studies of neutrophil type 1 interferon responses are needed in this population.

13.
South Afr J HIV Med ; 25(1): 1539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444836

RESUMO

Background: Maternal electronic gatekeeping (eGK) codes for HIV viral load (VL) testing of pregnant and breastfeeding women were developed to permit increased frequency of maternal HIV VL testing without automated gatekeeping cancellation, and to enable virological surveillance. Objectives: This study describes the national uptake of maternal eGK codes and VL suppression (VLS) rates disaggregated by age during antenatal, delivery and postnatal periods in South Africa during 2022. Method: HIV VL tests associated with C#PMTCT (used for antenatal and postnatal testing) and C#DELIVERY (used at delivery) eGK codes between 01 January and 31 December 2022, were extracted from the National Institute for Communicable Diseases Data Warehouse. Uptake of eGK codes was calculated using indicators from the District Health Information System as denominators while HIV VLS rates (< 1000 copies/mL) were calculated as monthly and annual percentages. Results: Overall, national maternal eGK code uptake was 41.8%, 24.5% and 0.12% for the antenatal, delivery and postnatal periods, respectively. The monthly antenatal eGK uptake increased from 27.5% to 58.5% while delivery uptake increased from 17.3% to 30.0%. The overall annual maternal HIV VLS rate was 86.7% antenatally and 87.2% during delivery. The monthly average HIV VLS for adolescent girls and young women (AGYW) was 76.1% antenatally and 79.6% during delivery. Conclusion: Although overall national uptake of maternal HIV VL eGK codes was low, antenatal and delivery uptake improved over time, thereby facilitating use of eGK codes for programmatic monitoring of maternal VLS rates for the first time. Quality of care among pregnant AGYW requires urgent attention.

14.
Drug Chem Toxicol ; 47(4): 386-403, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38348658

RESUMO

Worldwide, acute antipsychotic poisoning results in high morbidities and mortalities. Though extrapyramidal syndromes are commonly associated, the extent of extrapyramidal syndromes in relation to the severity of antipsychotic poisoning has not been addressed yet. Thus, this study aimed to assess the Global Dystonia Rating Scale (GDRS) as an unfavorable outcomes predictive tool in acute antipsychotic poisoning. A cross-sectional study included 506 antipsychotic-poisoned patients admitted to Tanta University Poison Control Center, Egypt, over three years was conducted. The mean GDRS was 9.1 ± 16.7 in typical antipsychotic poisoning, which was significantly higher than that of atypical antipsychotics (4.2 ± 11.5) (p = 0.003). Patients with GDRS> 20 showed significantly higher liability for all adverse outcomes (p < 0.05). However, poisoning with typical antipsychotics was associated with significantly more cardiotoxicity (p = 0.042), particularly prolonged QRS (p = 0.005), and intensive care unit (ICU) admission (p = 0.000). In contrary to the PSS, which failed to predict the studied adverse outcomes, GDRS significantly predicted all adverse outcomes (p < 0.000) for all antipsychotic generations. In atypical antipsychotics, GDRS above three accurately predicted cardiotoxicities, prolonged QTc interval, and respiratory failure with Area under curves (AUC) of 0.937, 0.963, and 0.941, respectively. In typical antipsychotic poisoning, at higher cutoffs (7.5, 27.5, 18, and 7.5), cardiotoxicities, prolonged QTc interval, and respiratory failure were accurately predicted (AUC were 0.974, 0.961, and 0.960, respectively). GDRS is an objective, substantially useful tool that quantifies dystonia and can be used as an early reliable predictor of potential toxicity in acute antipsychotic poisoning.


Assuntos
Antipsicóticos , Distonia , Humanos , Antipsicóticos/intoxicação , Antipsicóticos/efeitos adversos , Masculino , Feminino , Estudos Transversais , Adulto , Distonia/induzido quimicamente , Egito , Adulto Jovem , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adolescente , Valor Preditivo dos Testes
15.
Chembiochem ; 25(6): e202300813, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38227784

RESUMO

AMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of TARP γ-8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel 18 F-labeled TARP γ-8 inhibitors and their corresponding precursors, stemming from the azabenzimidazole scaffold. The resulting radioligands [18 F]TARP-2204 and [18 F]TARP-2205 were successfully synthesized with acceptable radiochemical yield, high molar activity, and excellent radiochemical purity. In vitro autoradiography demonstrates high level of specific binding of [18 F]TARP-2205 to TARP γ-8 in both rat and nonhuman primate brain tissues. However, unexpected radiodefluorination in PET imaging studies of rodents emphasizes the need for further structural refinement. This work serves as an excellent starting point for the development of future 18 F-labeled TARP γ-8 PET tracers, offering valuable insights into medicinal chemistry design, radiosynthesis and subsequent PET evaluation.


Assuntos
Tomografia por Emissão de Pósitrons , Receptores de AMPA , Ratos , Animais , Receptores de AMPA/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Hipocampo
16.
Poult Sci ; 103(3): 103457, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295500

RESUMO

This study used 300 1-day-old, sexless, developing chicks of Japanese quail to estimate the ability of vitamin C and/or garlic to antagonize the venomous influence of cadmium (Cd) on the hematological, immunological, and performance characteristics of developing Japanese quail. The quail was separated into 5 similar groups of 60 chicks apiece, and 6 duplicates (10 each) were given to each sub-group. The control group received a basal diet without any supplements. The Cd group was nourished with a basal diet of + 80 mg cadmium chloride (CdCl2)/kg diet. The 3rd group was fed a basal diet + 80 mg CdCl2/kg diet and complemented with a 200 mg Vitamin C (Cd + C)/kg diet. The 4th group was nourished with a basal diet + 80 mg CdCl2/kg diet and complemented by a 500 mg dried garlic powder (Cd + G)/kg diet. The 5th group was fed a basal diet + 80 mg CdCl2/kg diet, complemented by a 200 mg vitamin C/kg diet + 500 mg dried garlic powder (Cd + CG)/kg diet. Results showed that in the 5th group in which cadmium was added together with Vit C + garlic, there was an improvement in both live weight gain (1-42 d) and feed consumption (1-21 and 1-42 d ) compared to the group in which Cd was added alone. The addition of Vit C alone and together with garlic seems to completely improve the cadmium-related increase in alkaline phosphatase (ALP), and Aspartate aminotransferase (AST), and Malondialdehyde (MDA) levels when compared to the control. Compared to cadmium-polluted diets, quail that got cadmium and feed additives significantly reduced cadmium residue. In addition, the cadmium group's serum immunoglobulin M (IgM) level decreased significantly. These data imply that dietary supplementation with (C) or (G) may be beneficial in retrogressing the drop in immunoglobulin G (IgG) and IgM caused by Cd and minimizing Cd's deleterious influence on immunity.


Assuntos
Ácido Ascórbico , Alho , Animais , Ácido Ascórbico/farmacologia , Coturnix , Cádmio/toxicidade , Pós , Galinhas , Antioxidantes/farmacologia , Vitaminas , Suplementos Nutricionais , Dieta/veterinária , Codorniz , Imunoglobulina M , Ração Animal/análise
17.
Cancers (Basel) ; 16(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38254902

RESUMO

Weight loss is a significant health problem among patients with head and neck cancer (HNC) that is attributable primarily to the tumor or tumor therapy. Critical weight loss (CWL) is defined as the unintentional loss of ≥5% of weight. Therefore, this study's goal was to investigate and determine the possible factors influencing CWL among patients with HNC who have received radiotherapy or concurrent chemoradiotherapy (CCRT). We conducted a retrospective analysis of 175 patients who received radiotherapy or CCRT as either their primary, adjuvant, or combined treatment at the Oncology Center in King Abdullah Medical City. All patients were ≥18 years of age and diagnosed with HNC with no metastasis. The study results showed that 107 patients (61%) had CWL, while 68 (39%) did not. The following factors were significantly predictive of CWL with a multivariate regression analysis: pretreatment BMI (AOR = 1.1, 95% CI = 1.02-1.17), oral cavity cancer (AOR = 10.36, 95% CI = 1.13-94.55), and male sex (AOR = 3.15, 95% CI = 1.39-7.11). In conclusion, weight loss is highly prevalent among HNC patients during treatment. Accordingly, pretreatment BMI, cancer in the oral cavity, and being male can be considered predictive factors for CWL.

18.
Int J Mol Sci ; 25(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38256175

RESUMO

Abnormal NAD+ signaling has been implicated in axonal degeneration in diabetic peripheral neuropathy (DPN). We hypothesized that supplementing NAD+ precursors could alleviate DPN symptoms through increasing the NAD+ levels and activating the sirtuin-1 (SIRT1) protein. To test this, we exposed cultured Dorsal Root Ganglion neurons (DRGs) to Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), which increased the levels of NAD+, the SIRT1 protein, and the deacetylation activity that is associated with increased neurite growth. A SIRT1 inhibitor blocked the neurite growth induced via NR or NMN. We then induced neuropathy in C57BL6 mice with streptozotocin (STZ) or a high fat diet (HFD) and administered NR or NMN for two months. Both the STZ and HFD mice developed neuropathy, which was reversed through the NR or NMN administration: sensory function improved, nerve conduction velocities normalized, and intraepidermal nerve fibers were restored. The NAD+ levels and SIRT1 activity were reduced in the DRGs from diabetic mice but were preserved with the NR or NMN treatment. We also tested the effect of NR or NMN administration in mice that overexpress the SIRT1 protein in neurons (nSIRT1 OE) and found no additional benefit from the addition of the drug. These findings suggest that supplementing with NAD+ precursors or activating SIRT1 may be a promising treatment for DPN.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Animais , Camundongos , Neuropatias Diabéticas/tratamento farmacológico , NAD , Diabetes Mellitus Experimental/complicações , Sirtuína 1 , Camundongos Endogâmicos C57BL , Nucleotídeos , Estreptozocina
19.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469343

RESUMO

Abstract Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferronis post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.


Resumo As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

20.
Braz. j. biol ; 84: e254552, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360202

RESUMO

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.


As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.


Assuntos
Animais , Ratos , Ratos Wistar , Solanum lycopersicum , Fígado/efeitos dos fármacos , Antituberculosos
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