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3.
Sci Rep ; 14(1): 21599, 2024 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284902

RESUMEN

Mentha arvensis is an herbaceous plant commonly known as peppermint or Japanese mint. This study investigated the toxic potential and repellent efficacy of M. arvensis essential oil (MaEO) at varying concentrations (15.625-250 mg/mL) in Nauphoeta cinerea, along with its impact on biochemical parameters in N. cinerea. The potential of the major compounds as a new analgesic target was investigated using molecular docking. The essential oil was analyzed by gas Chromatography-mass spectrometry (GC-MS) and the toxic potential, repellent property, and changes in lipid peroxidation (LPO) levels were evaluated as markers of oxidative stress. GC-MS results revealed that the main components were oxygenated monoterpenes such as menthol (71.31%), mentone (13.34%) and isomentone (5.35%). MaEO significantly reduced lipid peroxidation (LPO), the levels of non-protein thiols and iron(II) at the concentration of 125 mg/mL in N. cinerea. Furthermore, the major components, L-(-)-Menthol and menthone demonstrated high gastrointestinal absorption and high affinity with the target protein, suggesting possible links that contribute to the analgesic effect of MaEO.


Asunto(s)
Antioxidantes , Peroxidación de Lípido , Mentha , Aceites Volátiles , Mentha/química , Antioxidantes/farmacología , Antioxidantes/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Peroxidación de Lípido/efectos de los fármacos , Animales , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Repelentes de Insectos/farmacología , Repelentes de Insectos/química , Aceites de Plantas/farmacología , Aceites de Plantas/química
4.
Headache ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248024

RESUMEN

BACKGROUND: Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting. OBJECTIVE: This study aimed to evaluate the effect of extended-release paracetamol on preventing fasting headaches. METHODS: A randomized, open-label clinical trial investigated the efficacy of extended-release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self-reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan. RESULTS: A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (ß = -0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42-1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12-0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13-0.82). No adverse effects were observed during the study period. CONCLUSION: No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan.

5.
Patient Prefer Adherence ; 18: 2019-2026, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39345761

RESUMEN

Background: Improving health literacy has been found to play a significant role in enhancing medication adherence in patients with type 2 diabetes. Purpose: The present study aims to evaluate health literacy and its association with medication adherence among diabetic patients in Jordan. Patients and Methods: This cross-sectional study included 400 diabetic patients, predominantly female (68.8%), with a median age of 58 years, attending the endocrinology outpatient clinic at Albasheer Hospital in Amman, Jordan, between August and December 2023. Patients were recruited using convenience sampling, including those aged 18 and older, literate, diagnosed with T2DM for at least one year, and on at least one medication for T2DM. Sample size was calculated based on the Events Per Variable (EPV) criterion to ensure sufficient power for logistic regression analysis. Data were collected using two validated instruments: the Jordanian Diabetic Health Literacy Questionnaire (JDHLQ), assessing health literacy, and the Medication Adherence Report Scale (MARS-5), measuring medication adherence. A binary logistic regression model was constructed to identify variables associated with adherence levels. Results: The study enrolled 400 diabetic patients (females =68.8%). While most of the participants (70.3%) reported high adherence levels, results revealed a window for health literacy improvement as the median for the JDHLQ score was 22 (ranging from 18 to 25) out of a maximum possible score of 32. More than half of the participants replied "never" to "I forget to take my medications", followed by "I stop taking my medications for a while". Conclusion: The binary regression model revealed that a higher JDHLQ score significantly increased the odds of a high adherence level. The significant association between improved health literacy and medication adherence necessitates the implementation of educational campaigns for enhancing literacy and hence medication adherence among patients with type 2 diabetes.

6.
Saudi Pharm J ; 32(9): 102148, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39157423

RESUMEN

Drug addiction is considered a worldwide concern and one of the most prevailing causes of death globally. Opioids are highly addictive drugs, and one of the most common opioids that is frequently used clinically is fentanyl. The potential harmful effects of chronic exposure to opioids on the heart are still to be elucidated. Although ß-lactam antibiotics are well recognized for their ability to fight bacteria, its protective effect in the brain and liver has been reported. In this study, we hypothesize that ß-lactam antibiotic, ceftriaxone, and the novel synthetic non-antibiotic ß-lactam, MC-100093, are cardioprotective against fentanyl induced-cardiac injury by upregulating xCT expression. Mice were exposed to repeated low dose (0.05 mg/kg, i.p.) of fentanyl for one week and then challenged on day 9 with higher dose of fentanyl (1 mg/kg, i.p.). This study investigated cardiac histopathology and target genes and proteins in serum and cardiac tissues in mice exposed to fentanyl overdose and ß-lactams. We revealed that fentanyl treatment induced cardiac damage as evidenced by elevated cardiac enzymes (troponin I). Furthermore, fentanyl treatment caused large aggregations of inflammatory cells and elevation in the areas and volumes of myocardial fibers, indicating hypertrophy and severe cardiac damage. Ceftriaxone and MC-100093 treatment, However, induced cardioprotective effects as evidenced by marked reduction in cardiac enzymes (troponin I) and changes in histopathology. Furthermore, ceftriaxone and MC-100093 treatment decreased the levels of hypertrophic genes (α-MHC & ß-MHC), apoptotic (caspase-3), and inflammatory markers (IL-6 & NF-κB). This study reports for the first time the cardioprotective effect of ß-lactams against fentanyl-induced cardiac injury. Further studies are greatly encouraged to completely identify the cardioprotective properties of ceftriaxone and MC-100093.

7.
Toxics ; 12(8)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39195706

RESUMEN

Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and ß-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using ß-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography-mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the ß-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that ß-lactams may be promising drugs for treating fentanyl use disorder.

8.
Front Immunol ; 15: 1426496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050858

RESUMEN

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multi-epitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of -329.46 (kcal/mol) for TLR-3 and -358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety.


Asunto(s)
Biología Computacional , Epítopos de Linfocito B , Vacunas Virales , Infección por el Virus Zika , Virus Zika , Virus Zika/inmunología , Vacunas Virales/inmunología , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/inmunología , Humanos , Epítopos de Linfocito B/inmunología , Biología Computacional/métodos , Desarrollo de Vacunas , Simulación del Acoplamiento Molecular , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/química , Modelos Moleculares , Inmunoinformática
9.
Hum Vaccin Immunother ; 20(1): 2381297, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39036977

RESUMEN

Vaccine literacy is a significant part of health literacy. Although several tools have been developed to assess vaccine literacy, such tools are lacking in Arabic. Validating an Arabic version of a tool that evaluates vaccine literacy is critically important, as it would aid in understanding the decision-making process regarding vaccinations among individuals in Arabic-speaking countries. Therefore, the current study aimed to validate an Arabic tool for assessing vaccine literacy in adult vaccination. An online questionnaire was distributed to people throughout Jordan by sharing the questionnaire link via various social media platforms. The reliability and validity of the Arabic version of the vaccination literacy assessment tool (HLVa-Ar) were evaluated using factor analysis and Rasch analyses. The two-factor model generated fit indices were in the acceptable range (χ2/df = 2.48, RMSEA = 0.06, SRMR = 0.05, GFI = 0.94, CFI = 0.97, and TLI = 0.96). Cronbach's alpha for functional Vaccination literacy (VL) and interactive/critical VL were 0.91 and 0.88 respectively. The Rasch analysis indicated acceptable infit/outfit values and high item and person separation reliabilities for the two factors (0.852, 0.868, and 0.771, 0.818 respectively). Overall, the 420 participants displayed a good understanding of the general benefits and importance of vaccination. The HLVa-Ar was shown to be a valid and reliable tool that portrayed a wide range of vaccination literacy levels in the studied sample and provided valuable insights into participants' vaccination knowledge. The findings emphasize the need for developing targeted strategies to improve vaccination literacy and increase vaccination rates.


Asunto(s)
Alfabetización en Salud , Vacunación , Humanos , Femenino , Masculino , Encuestas y Cuestionarios , Adulto , Vacunación/psicología , Adulto Joven , Jordania , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adolescente , Análisis Factorial , Conocimientos, Actitudes y Práctica en Salud , Anciano
10.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063010

RESUMEN

Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice (Leprdb/db mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the Leprdb/db animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in Leprdb/db untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in Leprdb/db control mice than in all remaining groups. Identifying the factors that increase the BBB in Leprdb/db mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.


Asunto(s)
Barrera Hematoencefálica , Diabetes Mellitus Tipo 2 , Modelos Animales de Enfermedad , Receptores de Leptina , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Ratones , Receptores de Leptina/metabolismo , Receptores de Leptina/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Fluoresceína/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Subunidad beta de la Proteína de Unión al Calcio S100/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Masculino , Diabetes Mellitus Experimental/metabolismo , Permeabilidad , Ratones Endogámicos C57BL
11.
Eur J Pharmacol ; 978: 176792, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38950834

RESUMEN

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.


Asunto(s)
Modelos Animales de Enfermedad , Electroencefalografía , Lacosamida , Fármacos Neuroprotectores , Pregabalina , Topiramato , Animales , Lacosamida/farmacología , Lacosamida/uso terapéutico , Topiramato/farmacología , Topiramato/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Masculino , Pregabalina/farmacología , Pregabalina/uso terapéutico , Ratas , Conducta Animal/efectos de los fármacos , Epilepsia Refractaria/tratamiento farmacológico , Quimioterapia Combinada , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Hipocampo/patología , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/inducido químicamente , Estado Epiléptico/fisiopatología , Ratas Wistar , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/inducido químicamente
12.
Front Public Health ; 12: 1396255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011325

RESUMEN

Background: Mental health literacy (MHL) research in Jordan is sparse and validated MHL measures are lacking. The present study validated a Jordanian version of the Mental Health Literacy Scale (MHLS) and examined Jordanian individuals' MHL. Method: A Google Forms survey was designed, and the link was shared through various Jordanian social media platforms. Factor analysis and Rasch analysis were performed to validate the Jordanian version of the MHLS. Binary logistic regression was performed to assess variables associated with MHL. Results: The Jordanian MHLS was administered to 974 participants (74.4% females; median age 27 years). The mean MHL score of the participants was 71.1% indicating average literacy levels. The factor analysis indicated that 27 items distributed across four factors had the best model fit. The Rasch analysis confirmed item separation reliability and person reliability. The regression showed a correlation between educational attainment, income, marital status and MHL level. These findings emphasize the role of educational attainment in MHL, pointing to the necessity of integrating mental health education into formal curricula to enhance MHL across all societal levels. Stigma and limited-service availability act as barriers to mental health service and access, which compound the challenge of improving MHL. Targeted educational interventions and policy reforms may help improve MHL, thereby contributing to improving mental health outcomes in Jordan and potentially other similar settings.


Asunto(s)
Alfabetización en Salud , Salud Mental , Humanos , Jordania , Alfabetización en Salud/estadística & datos numéricos , Femenino , Masculino , Adulto , Análisis Factorial , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Persona de Mediana Edad , Psicometría , Adulto Joven , Adolescente
13.
Healthcare (Basel) ; 12(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38998830

RESUMEN

BACKGROUND: the variations in a child's overall body shape and figure among different countries are attributable to differences in genetics, environmental factors, and the interaction between these elements. This study aims to evaluate the validity, reliability, and appropriateness of applying international growth standards to Jordanian children and adolescents aged 2-19 years old. METHODS: 65,828 Jordanian children and adolescents (43% males; 57% females) aged 2-19 years old were selected from the Hakeem Program database and various private schools across Jordan. Height-for-age, weight-for-age, and body mass index (BMI)-for-age were analyzed comparatively for Jordanian children and adolescents against international growth standards. The z-score for each record was computed based on international equations. RESULTS: Mean z-scores for height-for-age, weight-for-age, and BMI-for-age for both genders showed significant deviation from international standards across most age intervals. It was found that in most age groups, Jordanian children and adolescents were shorter and lighter than CDC and WHO standards, except for females at ages ≥ 16 years, who were heavier with higher BMI-for-age values than CDC standards based on weight-for-age and BMI-for-age equations. Moreover, Jordanian males at ages ≥ 12 years had lower BMI-for-age values than CDC standards. CONCLUSIONS: Jordanian children and adolescents showed significant deviations in their measurements from international standards and growth reference values. The development of a population-specific growth chart is highly recommended to enhance the accuracy of evaluating children's and adolescents' wellness.

14.
Saudi Pharm J ; 32(7): 102108, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38868175

RESUMEN

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-ß) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-ß mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

15.
Drug Dev Ind Pharm ; 50(6): 511-523, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38718267

RESUMEN

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.


Asunto(s)
Administración Cutánea , Antibacterianos , Cefepima , Quitosano , Geles , Tamaño de la Partícula , Absorción Cutánea , Piel , Quitosano/química , Cefepima/administración & dosificación , Cefepima/farmacocinética , Cefepima/química , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/química , Antibacterianos/farmacología , Geles/química , Animales , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Ratas , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Pruebas de Sensibilidad Microbiana , Masculino , Portadores de Fármacos/química , Nanopartículas/química , Ratas Wistar
16.
Sci Rep ; 14(1): 11410, 2024 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-38762658

RESUMEN

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.


Asunto(s)
Ácido 3,4-Dihidroxifenilacético , Diseño de Fármacos , Inhibidores de Glicósido Hidrolasas , Simulación del Acoplamiento Molecular , Bases de Schiff , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/síntesis química , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , Ácido 3,4-Dihidroxifenilacético/análogos & derivados , Ácido 3,4-Dihidroxifenilacético/química , Ácido 3,4-Dihidroxifenilacético/metabolismo , Ácido 3,4-Dihidroxifenilacético/farmacología , Bases de Schiff/química , Bases de Schiff/farmacología , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Relación Estructura-Actividad
17.
BMJ Open Respir Res ; 11(1)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38719502

RESUMEN

INTRODUCTION: The COVID-19 pandemic continues to be a global threat to public health, with over 766 million confirmed cases and more than 6 million reported deaths. Patients with a smoking history are at a greater risk of severe respiratory complications and death due to COVID-19. This study investigated the association between smoking history and adverse clinical outcomes among COVID-19 patients admitted to a designated medical centre in Saudi Arabia. METHODS: A retrospective observational cohort study was conducted using patient chart review data from a large tertiary medical centre in the eastern region of the country. Patients admitted between January and December 2020 were screened. The inclusion criteria were ≥18 years of age and confirmed COVID-19 infection via reverse-transcription-PCR. The exclusion criteria were unconfirmed COVID-19 infection, non-COVID-19 admissions, unconfirmed smoking status, vaccinated individuals, essential chart information missing or refusal to consent. Statistical analyses comprised crude estimates, matching weights (as the main analysis) and directed acyclic graphs (DAGs) causal pathway analysis using an ordinal regression model. RESULTS: The sample comprised 447 patients (never-smoker=321; ever-smoker=126). The median age (IQR) was 50 years (39-58), and 73.4% of the sample were males. A matching weights procedure was employed to ensure covariate balance. The analysis revealed that the odds of developing severe COVID-19 were higher in the ever-smoker group with an OR of 1.44 (95% CI 0.90 to 2.32, p=0.130). This was primarily due to an increase in non-invasive oxygen therapy with an OR of 1.05 (95% CI 0.99 to 1.10, p=0.101). The findings were consistent across the different analytical methods employed, including crude estimates and DAGs causal pathway analysis. CONCLUSION: Our findings suggest that smoking may increase the risk of adverse COVID-19 outcomes. However, the study was limited by its retrospective design and small sample size. Further research is therefore needed to confirm the findings.


Asunto(s)
COVID-19 , Puntaje de Propensión , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Arabia Saudita/epidemiología , Adulto , Índice de Severidad de la Enfermedad , Fumar Tabaco/epidemiología , Fumar Tabaco/efectos adversos , Anciano , Factores de Riesgo , Hospitalización/estadística & datos numéricos
18.
Healthcare (Basel) ; 12(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38727504

RESUMEN

(1) Background: First aid administered during road accidents can save millions of lives. However, the knowledge and attitudes of the Jordanian population towards first aid are lacking. This study aimed to examine the knowledge, attitudes, and barriers to performing first aid among the Jordanian population during road accidents. (2) Methods: An online questionnaire was developed and distributed using various Jordanian social media platforms. The questionnaire collected the participants' sociodemographic details and assessed their first aid knowledge, attitudes toward first aid, and barriers preventing the participants from performing first aid in emergencies. (3) Results: 732 participants participated in this study. The median knowledge score regarding first aid items was 9 (7-10) out of the maximum possible score of 15. The median first aid attitude score was 24 (22-27) out of a maximum possible score of 30. The most commonly reported barrier to performing first aid among the participants was "lack of first aid training" (76.78%), followed by "lack of knowledge about first aid" (75.81%) and "fear of performing first aid" (57.51%). The participants with lower income levels exhibited more negative attitudes towards first aid (4). Conclusions: This study underscores the urgent need for enhanced first aid training and awareness in Jordan. The participants' first-aid knowledge overall was limited, although positive attitudes toward first-aid delivery were observed. The findings emphasize the need for regular and structured first-aid training courses, addressing barriers such as fear and misinformation and ensuring accessibility across all socioeconomic levels to improve preparedness for road traffic accidents and other emergencies. This comprehensive approach can better equip the Jordanian population to effectively manage emergencies and improve public health outcomes.

19.
Biomedicines ; 12(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38790905

RESUMEN

Contamination by fungi and the toxins they secrete is a worldwide health concern. One such toxin is zearalenone (Zea), which is structurally similar to the hormone estrogen, interferes with its action on the reproductive system, and is therefore classified as an endocrine disruptor. This study aims to determine the effectiveness of hispidin and magnesium nanoparticles (MgONPs) against zearalenone-induced myotoxicity, which causes polycystic ovary syndrome (PCOS) in rats. A three-month exposure study was performed using female Wistar rats (n = 42) with an average weight of 100-150 g. The animals were divided into six groups (I to VI) of seven rats each. Group I was administered distilled water as a negative control. Group II was exposed to Zea 0.1 mg/kg b.w. through gavage daily. Group III was treated with 0.1 mg/kg of hispidin through gavage daily. Group IV was given 150 µg/mL MgONPs orally each day. Group V was treated with Zea 0.1 mg/kg b.w. + 0.1 mg/kg hispidin orally each day. Group VI was treated with Zea 0.1 mg/kg b.w. and the combination treatment of 0.1 mg/kg hispidin + 150 µg/mL MgONPs through gavage every day. The effectiveness of hispidin and MgONPs against Zea toxicity was evaluated in terms of ovarian histological changes, gene expression, oxidative stress biomarkers, biochemical variables, and hormone levels. The findings showed that exposure to Zea promotes PCOS in rats, with Zea-treated rats displaying hyper-ovulation with large cysts; elevated testosterone, luteinizing hormone, insulin, and glucose; and reduced sex hormone-binding globulin. In addition, qRT-PCR for aromatase (Cyp19α1) showed it to be downregulated. Treatment with hispidin improved the histopathological and hormonal situation and rescued expression of Cyp19α. Our data indicate the potential therapeutic effects of hispidin against Zea-induced Fungal Toxicity.

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