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1.
Pediatr Int ; 65(1): e15620, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37735838

RESUMEN

BACKGROUND: This study aimed to evaluate the demographics, clinical characteristics, risk factors, and antibiotic resistance of pediatric community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing uropathogens. METHODS: This retrospective study was conducted at a tertiary care hospital in Saudi Arabia, among children aged between 0 and 14 years, with a culture-proven diagnosis of community-acquired UTI between February 2019 and September 2021. Patients were divided into two groups based on whether or not their UTI was caused by ESBL-producing bacteria. RESULTS: A total of 383 patients with community-acquired UTI were evaluated. Escherichia coli was detected in 72.6% of cultures. Extended-spectrum beta-lactamase-producing organisms were responsible for 35.7% of UTI episodes. Of these 69% and 31% were caused by E. coli and Klebsiella pneumoniae, respectively. There were no significant differences between the two groups with regard to clinical presentation or urine analysis. The resistance rates in the ESBL-producing group were 39.4% for amoxicillin/clavulanic acid, 65.7% for ciprofloxacin, 72.3% for co-trimoxazole, 32.8% for nitrofurantoin, 21.2% for gentamicin, and 0.7% for amikacin and carbapenems. In the non-ESBL-producing group, it was 22.4% for amoxicillin/clavulanic acid, 22.4% for ciprofloxacin, 38.2% for co-trimoxazole, 23.6% for nitrofurantoin, 6.1% for gentamicin, and zero for amikacin and carbapenems. The presence of renal abnormalities (p = 0.014) and male gender (p = 0.026) were determined to be independent risk factors for ESBL UTIs. CONCLUSIONS: Recognizing risk factors and antibiotic resistance for ESBL-producing bacteria may aid in tailoring an antibiotic regimen for pediatric patients at high risk of ESBL-UTIs.


Asunto(s)
Infecciones Comunitarias Adquiridas , Infecciones por Escherichia coli , Infecciones Urinarias , Humanos , Niño , Masculino , Recién Nacido , Lactante , Preescolar , Adolescente , Escherichia coli , Estudios Retrospectivos , Nitrofurantoína , Amicacina , Combinación Trimetoprim y Sulfametoxazol , beta-Lactamasas , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos , Combinación Amoxicilina-Clavulanato de Potasio , Gentamicinas , Ciprofloxacina , Pruebas de Sensibilidad Microbiana
2.
Heart Surg Forum ; 26(1): E134-E140, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36856492

RESUMEN

BACKGROUND: Due to its high morbidity and mortality after open-heart surgery, sternal wound infection (SWI) is one of the most important consequences to avoid and manage. AIM: To assess the incidence, risk factor, causative organisms, and mortality of SWIs in patients who had open-heart surgery over a 9-year period at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. METHODS: A retrospective study was done on 634 patients who underwent open heart surgery. Data was collected, including patient demographics, BMI, blood group, diabetes, hyperlipidemia, COPD, previous cardiac surgery, previous myocardial infarction, duration of the operation, blood transfusion during the operation, hospital length of stay, and bypass time with each type of sternal wound infection. RESULTS: The incidence of SSWI and DSWI was 8.6% and 4.1%, respectively. Coagulase-negative staphylococcus was the most frequently isolated organism from SSWI and DSWI patients. A concomitant diabetes mellitus that necessitates blood transfusion was identified as one of the risk variables for SSWI in a multivariate regression study. While concomitant diabetes, being a woman, and a lengthy hospital stay were independently linked with DSWI. Compared with the SSWI group, the 30-day mortality rate for DSWI patients was 3.8% as opposed to 3.7%, and the difference in survival was not statistically significant. Having an older, longer bypass time, and postoperative problems were independent risk factors for 30-day mortality. CONCLUSION: Future studies in various healthcare settings are required in order to generalize the results because this was a single center study.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Infarto del Miocardio , Femenino , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo
3.
Molecules ; 28(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36677532

RESUMEN

The analytical quality by design (AQbD) approach is utilized for developing and validating the simple, sensitive, cost-effective reverse-phase high performance liquid chromatographic method for the estimation of xanthohumol (XH) in bulk and nanoformulations. The Box-Behnken design (BBD) is applied for method optimization. The mobile phase ratio, pH and flow rate were selected as independent variables, whereas retention time, peak area, peak height, tailing factor, and theoretical plates were selected as dependent variables. The chromatogram of XH obtained under optimized conditions has given optimum conditions such as retention time (5.392 min), peak area (1,226,737 mAU), peak height (90,121 AU), tailing factor (0.991) and theoretical plates (4446.667), which are contoured in the predicted values shown by BBD. Validation of the method has been performed according to ICH Q2(R1) recommendations, using optimized conditions for linearity, limit of detection (LOD) and limit of quantification (LOQ), accuracy, precision, robustness and system suitability. All the values of validation parameters lie within the acceptable limits prescribed by ICH. Therefore, the developed and validated method of XH by the AQbD approach can be applied for the estimation of XH in bulk and various nanoformulations.


Asunto(s)
Cromatografía de Fase Inversa , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Fase Inversa/métodos , Límite de Detección
4.
Molecules ; 27(14)2022 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-35889428

RESUMEN

Cytokine storm is a condition in which the immune system produces an excessive number of inflammatory signals, which can result in organ failure and death. It is also known as cytokine release syndrome, CRS, or simply cytokine storm, and it has received a lot of attention recently because of the COVID-19 pandemic. It appears to be one of the reasons why some people experience life-threatening symptoms from COVID-19, a medical condition induced by SARS-CoV-2 infection. In situations where natural substances can be exploited as therapeutics to reduce cytokine storm, the drug development process has come to the rescue. In the present study, we tested the potentiality of Andrographolide, labdane diterpenoid targeting several key cytokines that are secreted as a result of cytokine storm. We used molecular docking analyses, molecular dynamics simulations, and pharmacokinetic properties to test the stability of the complexes. The compound's binding energy with some cytokines was over -6.5 Kcal/mol. Furthermore, a post-molecular dynamics (MD) study revealed that Andrographolide was extremely stable with these cytokines. The compound's pharmacokinetic measurements demonstrated excellent properties in terms of adsorption, distribution, metabolism, and excretion. Our research revealed that this compound may be effective in lowering cytokine storm and treating severe symptoms.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Diterpenos , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Citocinas , Diterpenos/farmacología , Diterpenos/uso terapéutico , Humanos , Simulación del Acoplamiento Molecular , Pandemias , SARS-CoV-2
5.
Molecules ; 27(20)2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36296708

RESUMEN

Xanthohumol (XH) a prenylated chalcone has diverse therapeutic effects against various diseases. In the present study, a bioanalytical method was developed for XH in rat plasma using reverse phase high performance liquid chromatography. The validation of the method was performed as per ICH M10 guidelines using curcumin as an internal standard. The Isocratic elution method was used with a run time of 10 min, wherein the mobile phase ratio 0.1% v/v OPA (A): Methanol (B) was 15:85 v/v at flow rate 0.8 mL/min and injection volume of 20 µL. The chromatograms of XH and curcumin was recorded at a wavelength of 370 nm. The retention time for XH and curcumin was 7.4 and 5.8 min, respectively. The spiked XH from plasma was extracted by the protein precipitation method. The developed method was linear with R2 value of 0.9996 over a concentration range of 50-250 ng/mL along with LLOQ. The results of all the validation parameters are found to be within the accepted limits with %RSD value less than 2 and the percentage recovery was found to be greater than 95%. Based on the %RSD and percentage recovery results it was confirmed that the method was precise and accurate among the study replicates. LOD and LOQ values in plasma samples were found to be 8.49 ng/mL and 25.73 ng/mL, respectively. The stability studies like freeze thaw, short term and long-term stability studies were also performed, %RSD and percentage recovery of the XH from plasma samples were within the acceptable limits. Therefore, the developed bioanalytical method can be used effectively for estimation of XH in plasma samples.


Asunto(s)
Chalconas , Curcumina , Ratas , Animales , Cromatografía Líquida de Alta Presión/métodos , Metanol , Reproducibilidad de los Resultados
6.
Pflugers Arch ; 473(1): 37-51, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33210151

RESUMEN

Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulation in mediating CB hyperactivity is currently unknown. This study evaluated whether beta-blocker treatment with propranolol (Prop) prevented the development of CB hyperactivity, vascular sympathetic nerve growth and hypertension caused by CIH. Adult male Wistar rats were assigned into 1 of 4 groups: Control (N), N + Prop, CIH and CIH + Prop. The CIH paradigm consisted of 8 cycles h-1, 8 h day-1, for 3 weeks. Propranolol was administered via drinking water to achieve a dose of 40 mg kg-1 day-1. Immunohistochemistry revealed the presence of both ß1 and ß2-adrenoceptor subtypes on the CB type I cell. CIH caused a 2-3-fold elevation in basal CB single-fibre chemoafferent activity and this was prevented by chronic propranolol treatment. Chemoafferent responses to hypoxia and mitochondrial inhibitors were attenuated by propranolol, an effect that was greater in CIH animals. Propranolol decreased respiratory frequency in normoxia and hypoxia in N and CIH. Propranolol also abolished the CIH mediated increase in vascular sympathetic nerve density. Arterial blood pressure was reduced in propranolol groups during hypoxia. Propranolol exaggerated the fall in blood pressure in most (6/7) CIH animals during hypoxia, suggestive of reduced sympathetic tone. These findings therefore identify new roles for ß-adrenergic stimulation in evoking CB hyperactivity, sympathetic vascular hyperinnervation and altered blood pressure control in response to CIH.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Cuerpo Carotídeo/efectos de los fármacos , Hipoxia , Propranolol/farmacología , Antagonistas Adrenérgicos beta , Animales , Dióxido de Carbono , Esquema de Medicación , Masculino , Ratas , Ratas Wistar , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Sistema Nervioso Simpático/efectos de los fármacos
7.
Crit Rev Eukaryot Gene Expr ; 31(2): 75-82, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34347981

RESUMEN

Polycystic ovarian syndrome (PCOS) is a heterogeneous, persistent endocrine disease that is generally identified in 6-10% of women of reproductive age. Intriguingly, about 55-65% of patients with PCOS display insulin resistance (IR), which can be related to their body weight, ethnicity, or age. Discovering the root cause of PCOS is of particular concern due to IR and abnormal androgen secretion, and continuous attempts have been made to define the complex pathogenic network underlying the syndrome. In addition, PCOS reflects connections between various proteins, genes, and epigenetics affected by environmental influences. Genetic factors such as mutation, epigenetics, and/or expression in noncoding RNAs, particularly miRNA222, play an important role in PCOS pathophysiology and cannot be neglected. Metformin has been used traditionally as a pillar of PCOS treatment, but even effective insulin sensitization therapy can contribute to side effects that reduce patient adherence and limit treatment effectiveness. Therefore, many of the PCOS characteristics can be taken into account for the impact on hyperinsulinemic ovaries which is important in order to develop treatment strategies. Thus our primary objective is to research the therapeutic efficacy of vitamin D in the suppression of miR222 and, secondary to miR222, mediated molecular pathways involving insulin resistance and metabolic defects, which influence ovarian activity, anovula-tion, and finally infertility.


Asunto(s)
Enfermedades Metabólicas/prevención & control , MicroARNs/antagonistas & inhibidores , Síndrome del Ovario Poliquístico/terapia , Vitamina D/uso terapéutico , Femenino , Humanos , Resistencia a la Insulina , Enfermedades Metabólicas/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Vitamina D/farmacología
8.
Eur J Clin Pharmacol ; 77(9): 1259-1274, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33686454

RESUMEN

AIM: This study aimed to undertake a systematic review and meta-analysis of global prevalence and types of complementary and alternative medicine (CAM) use amongst adults with diabetes. METHODS: Nine databases, including MEDLINE and EMBASE, were searched for studies published between 2009 and 2019 which included extractable data for CAM use in adult patients with diabetes. Study characteristics, types of CAM, and overall and subgroup prevalence data in relation to CAM use were extracted. Meta-analysis of aggregate level data on prevalence and prevalence ratios (PRs) was performed using a random effects model. RESULTS: From the 38 studies included in the review, a total of 37 types of CAM and 223 types of herbs were identified. Pooled prevalence of CAM use was 51%. A wide variation in prevalence rates (predictive interval 8-93%) was observed. In the context of high heterogeneity, we found no evidence that CAM use was associated with gender, chronicity or type of diabetes. Approximately one third of patients did not disclose their use of CAM to healthcare professionals (95% PrI 25%, 97%). Herbal medicines, acupuncture, homoeopathy and spiritual healing were the common CAM types reported. CONCLUSIONS: A wide variation in prevalence of CAM use by patients with diabetes was identified. Healthcare professionals should be aware of their patients' use of CAM to ensure treatment optimization, avoid herb-drug interactions and promote medication adherence in diabetes. Diabetic reviews and clinical guidelines should incorporate exploration of patient use of CAM as many patients do not proactively disclose the use of CAM to their healthcare professionals. REGISTRATION: The protocol for this study was registered with the Centre for Review and Dissemination (CRD). Protocol registration number CRD42019125036.


Asunto(s)
Terapias Complementarias/métodos , Terapias Complementarias/estadística & datos numéricos , Diabetes Mellitus/terapia , Terapias Complementarias/efectos adversos , Interacciones de Hierba-Droga , Humanos , Factores Sociodemográficos
9.
J Biochem Mol Toxicol ; 35(9): e22849, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34309957

RESUMEN

Growing cannabis efficacy, usage frequency, legal supply, and declining awareness of danger recently led to expanded United States cannabis exposure. In turn, cannabis use among elderly people over 50 has more than tripled in a decade and has contributed toward a positive association of cannabis use with pathological conditions, which include type II diabetes, metabolic syndrome, neurovascular and cardiovascular disease. Remarkably, all these outcome results are mediated by the involvement of the ATP-sensitive K+ channel. Cardiovascular compromise is a common syndrome in preterm infants that leads to incidence and death and has been distinguished by poor systemic flow or hypotension. Conditions of cardiovascular compromise include vasodysregulation and myocardial malfunction through dysfunctional ß-adrenergic activity. To avoid organ hypoperfusion progressing to tissue hypoxia-ischemia, inotropic drugs are used. Many premature children, however, respond insufficiently to inotropic activity with adrenergic agonists. The clinical disturbance including myocardial dysfunction through the activation of the ATP-sensitive K+ channel is often involved and the comparative efficacy of the nonpsychotropic cannabinoid, abnormal cannabidiol (Abn-CBD) is not yet known. Therefore, our primary aim was to investigate the molecular exploration of the cannabinoid system specifically Abn-CBD in cardiovascular protection involving dysregulated KATP.


Asunto(s)
Enfermedades Cardiovasculares , Recien Nacido Prematuro , Canales KATP/metabolismo , Receptores Adrenérgicos beta/metabolismo , Resorcinoles/uso terapéutico , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
J Appl Toxicol ; 41(10): 1649-1659, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33629778

RESUMEN

Tebuconazole is a widely used fungicide in agriculture, and it may easily enter in the human food chain. In addition, tebuconzaol skin permeation coefficient (Log Kp) is -5.55 cm/s and it does not violate Lipinski's rule. It may mimic as a ligand for various endocrine and reproductive receptor leading to toxicological response or disease manifestation. We studied interactive potential of tebuconazole with thyroid and sex hormone-binding globulin. The main methods for this in silico analyses are molecular docking and molecular dynamic (MD) simulation. This paper explores how agriculture fungicide tebuconzaol exposure can be a risk for endocrine and reprotoxicity due to its stable interactive potency with thyroid and sex hormone-binding globulin (2CEO and 1D2S). Thyroid impairment is one of the most common endocrine issues in human health. In molecular docking analyses, tebuconazole exhibited binding potency of -6.28 kcal/mol with 2CEO compared to its native ligand thyroxin and inhibitor propylthiouracil which had the binding potency of -9.9 and -4.49 kcal/mol, respectively. The binding score of tebuconzaol with 1D2S was found to be -7.54 kcal/mol compared to native ligand dihydrotestosteron and inhibitor aminoglutethimide which exhibited the binding score of -6.84 and -11.41 kcal/mol, respectively. Therefore, each complex was subjected to MD simulation for comparative assessment of physical movement. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), Radius of Gyration and hydrogen bonding exhibited that fluconazole had stable binding pattern with 2CEO and 1D2S which was almost similar to native ligand and its inhibitor. Study revealed that tebuconazole may lead to potent endocrine and reproductive disruptions.


Asunto(s)
Disruptores Endocrinos/toxicidad , Fungicidas Industriales/toxicidad , Simulación del Acoplamiento Molecular , Fenómenos Fisiológicos Reproductivos/efectos de los fármacos , Globulina de Unión a Hormona Sexual/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Triazoles/toxicidad , Adulto , Disruptores Endocrinos/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Globulina de Unión a Hormona Sexual/química , Glándula Tiroides/química , Triazoles/química
11.
Int J Mol Sci ; 22(11)2021 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-34067305

RESUMEN

Leukemia is persistently a significant cause of illness and mortality worldwide. Urolithins, metabolites of ellagic acid and ellagitannins produced by gut microbiota, showed better bioactive compounds liable for the health benefits exerted by ellagic acid and ellagitannins containing pomegranate and walnuts. Here, we assessed the potential antileukemic activities of both urolithin A and urolithin B. Results showed that both urolithin A and B significantly inhibited the proliferation of leukemic cell lines Jurkat and K562, among which urolithin A showed the more prominent antiproliferative capability. Further, urolithin treatment alters leukemic cell metabolism, as evidenced by increased metabolic rate and notable changes in glutamine metabolism, one-carbon metabolism, and lipid metabolism. Next, we evidenced that both urolithins equally promoted apoptosis in leukemic cell lines. Based on these observations, we concluded that both urolithin A and B alter leukemic cell metabolome, resulting in a halt of proliferation, followed by apoptosis. The data can be used for designing new combinational therapies to eradicate leukemic cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Cumarinas/farmacología , Leucemia/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ácido Elágico/farmacología , Frutas/química , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Taninos Hidrolizables/farmacología , Juglans/química , Células Jurkat , Células K562 , Metabolismo de los Lípidos/efectos de los fármacos , Nueces/química , Granada (Fruta)/química
12.
Int J Mol Sci ; 21(17)2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32825527

RESUMEN

The carotid body (CB) is an important organ located at the carotid bifurcation that constantly monitors the blood supplying the brain. During hypoxia, the CB immediately triggers an alarm in the form of nerve impulses sent to the brain. This activates protective reflexes including hyperventilation, tachycardia and vasoconstriction, to ensure blood and oxygen delivery to the brain and vital organs. However, in certain conditions, including obstructive sleep apnea, heart failure and essential/spontaneous hypertension, the CB becomes hyperactive, promoting neurogenic hypertension and arrhythmia. G-protein-coupled receptors (GPCRs) are very highly expressed in the CB and have key roles in mediating baseline CB activity and hypoxic sensitivity. Here, we provide a brief overview of the numerous GPCRs that are expressed in the CB, their mechanism of action and downstream effects. Furthermore, we will address how these GPCRs and signaling pathways may contribute to CB hyperactivity and cardiovascular and respiratory disease. GPCRs are a major target for drug discovery development. This information highlights specific GPCRs that could be targeted by novel or existing drugs to enable more personalized treatment of CB-mediated cardiovascular and respiratory disease.


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Cuerpo Carotídeo/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Enfermedades Respiratorias/metabolismo , Adenosina/metabolismo , Animales , Enfermedades Cardiovasculares/fisiopatología , Cuerpo Carotídeo/fisiopatología , Dopamina/metabolismo , Epinefrina/metabolismo , Humanos , Hipoxia/metabolismo , Transducción de Señal , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/fisiopatología
13.
Allergy ; 74(8): 1533-1548, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30844087

RESUMEN

BACKGROUND: Research into drug hypersensitivity associated with the expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no attention given to reactive metabolites. For this reason, we have studied HLA-B*13:01-linked dapsone hypersensitivity to (a) explore whether the parent drug and/or nitroso metabolite activate T cells and (b) determine whether HLA-B*13:01 is involved in the response. METHODS: Peripheral blood mononuclear cells (PBMC) from six patients were cultured with dapsone and nitroso dapsone, and proliferative responses and IFN-γ release were measured. Dapsone- and nitroso dapsone-specific T-cell clones were generated and phenotype, function, HLA allele restriction, and cross-reactivity assessed. Dapsone intermediates were characterized by mass spectrometry. RESULTS: Peripheral blood mononuclear cells from six patients and cloned T cells proliferated and secreted Th1/2/22 cytokines when stimulated with dapsone (clones: n = 395; 80% CD4+ CXCR3hi CCR4hi , 20% CD8+CXCR3hi CCR4hi CCR6hi CCR9hi CCR10hi ) and nitroso dapsone (clones: n = 399; 78% CD4+, 22% CD8+ with same chemokine receptor profile). CD4+ and CD8+ clones were HLA class II and class I restricted, respectively, and displayed three patterns of reactivity: compound specific, weakly cross-reactive, and strongly cross-reactive. Nitroso dapsone formed dimers in culture and was reduced to dapsone, providing a rationale for the cross-reactivity. T-cell responses to nitroso dapsone were dependent on the formation of a cysteine-modified protein adduct, while dapsone interacted in a labile manner with antigen-presenting cells. CD8+ clones displayed an HLA-B*13:01-restricted pattern of activation. CONCLUSION: These studies describe the phenotype and function of dapsone- and nitroso dapsone-responsive CD4+ and CD8+ T cells from hypersensitive patients. Discovery of HLA-B*13:01-restricted CD8+ T-cell responses indicates that drugs and their reactive metabolites participate in HLA allele-linked forms of hypersensitivity.


Asunto(s)
Dapsona/farmacología , Antígenos HLA-B/genética , Hipersensibilidad/etiología , Activación de Linfocitos/genética , Compuestos Nitrosos/farmacología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Adulto , Reacciones Cruzadas , Femenino , Expresión Génica , Antígenos HLA-B/inmunología , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/metabolismo , Inmunofenotipificación , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T/metabolismo
14.
J Infect Chemother ; 24(8): 623-631, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29753615

RESUMEN

Doxorubicin (DOX) is an anthracycline antibiotic that is used frequently for treatment of various types of malignancies. Hepatotoxicity is one of the serious complications of DOX. The aim of this study was to explore the effect of different doses of irbesartan on doxorubicin-induced hepatotoxicity in mice. Sixty male BALB/c mice were divided into six equal groups as follows: Control group; DOX group; Irbesartan (Small dose) group; Irbesartan (Large dose) group; DOX + Irbesartan (Small dose) group and DOX + Irbesartan (Large dose) group. Liver weight/body weight ratio, food intake, serum albumin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin were measured. Also, tissue antioxidant enzymes, transforming growth factor beta 1 (TGF-ß1), nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 (Nrf2/HO-1) content, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and signal transducer and activator of transcription-3 (STAT-3) were assessed. Parts of the hepatic tissues were subjected to histopathological examination. Irbesartan administration to DOX-treated mice induced significant decrease in serum ALT, AST, ALP, total bilirubin, tissue TGF-ß1, TNF-α, IL-6 and liver weight/body weight ratio associated with significant increase in food intake, serum albumin, tissue Nrf2/HO-1 content, STAT-3 and antioxidant enzymes and significant improvement in the histopathological picture compared to DOX group. This improvement was significant with DOX + Irbesartan large dose compared to DOX + Irbesartan small dose. In conclusion, irbesartan - in a dose-dependent manner - might represent a promising hope for cancer patients to ameliorate DOX-induced hepatotoxicity.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Antibióticos Antineoplásicos/efectos adversos , Compuestos de Bifenilo/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Doxorrubicina/efectos adversos , Tetrazoles/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Compuestos de Bifenilo/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Irbesartán , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Tetrazoles/uso terapéutico , Factor de Crecimiento Transformador beta1/metabolismo
15.
Chem Res Toxicol ; 30(12): 2174-2186, 2017 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-29045131

RESUMEN

Dapsone (DDS) causes hypersensitivity reactions in 0.5-3.6% of patients. Although clinical diagnosis is indicative of a hypersensitivity reaction, studies have not been performed to define whether dapsone or a metabolite activates specific T-cells. Thus, the aims of this study were to explore the immunogenicity DDS and nitroso DDS (DDS-NO) using peripheral blood mononuclear cells from healthy donors and splenocytes from mice and generate human T-cell clones to characterize mechanisms of T-cell activation. DDS-NO was synthesized from DDS-hydroxylamine and shown to bind to the thiol group of glutathione and human and mouse albumin through sulfonamide and N-hydroxyl sulphonamide adducts. Naïve T-cell priming to DDS and DDS-NO was successful in three human donors. DDS-specific CD4+ T-cell clones were stimulated to proliferate in response to drug via a MHC class II restricted direct binding interaction. Cross reactivity with DDS-NO, DDS-analogues, and sulfonamides was not observed. DDS-NO clones were CD4+ and CD8+, MHC class II and I restricted, respectively, and activated via a pathway dependent on covalent binding and antigen processing. DDS and DDS-NO-specific clones secreted a mixture of Th1 and Th2 cytokines, but not granzyme-B. Splenocytes from mice immunized with DDS-NO were stimulated to proliferate in vitro with the nitroso metabolite, but not DDS. In contrast, immunization with DDS did not activate T-cells. These data show that DDS- and DDS-NO-specific T-cell responses are readily detectable.


Asunto(s)
Dapsona/farmacología , Activación de Linfocitos/efectos de los fármacos , Compuestos Nitrosos/farmacología , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Dapsona/administración & dosificación , Dapsona/química , Voluntarios Sanos , Humanos , Espectrometría de Masas , Ratones , Estructura Molecular , Compuestos Nitrosos/administración & dosificación , Compuestos Nitrosos/química , Albúmina Sérica/química , Bazo/citología , Bazo/efectos de los fármacos , Linfocitos T/inmunología
16.
PeerJ ; 12: e17236, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38618572

RESUMEN

Purpose: Juniper (Juniperus procera) is a common forest tree species in Saudi Arabia. The decline in many populations of J. procera in Saudi Arabia is mainly due to seed dormancy and loss of natural regeneration. This study assessed the effects of chemical and hormonal treatments on seed germination and seedling growth in juniper plants. Methods: The seeds were subjected to either chemical scarification with 90% sulfuric acid and 20% acetic acid for 6 min or hormonal treatment by seed soaking in two concentrations (50 and 100 ppm) of three growth regulators, namely, indole acetic acid (IAA), gibberellins (GA3), and kinetin, for 72 h. A control group without any seed treatment was also prepared. The experiments were performed in an incubator maintained at room temperature and under a light and dark period of 12 h for 6 w. The germinated seeds for each treatment were counted and removed from the dishes. The selected germinated seeds from different treatments were planted in a greenhouse and irrigated with tap water for another 6 weeks. The hormone-treated seedlings were sprayed with their corresponding hormone concentrations 1 w after planting. Results: The highest percentage of seed germination was significantly recorded after seed soaking in 50 ppm GA3, whereas treatment with IAA (100 ppm) resulted in the best seedling growth. Seedlings treated with the three phytohormones showed a significant increase in photosynthetic pigments, total soluble sugars, proteins, percentage of oil, IAA, GA3, and kinetin contents of juniper seedlings compared with the control value, whereas abscisic acid content was decreased compared with chemical treatments. Conclusion: The investigated different treatments had an effective role in breaking seed dormancy and improving seedling growth of J. procera, which is facing a notable decline in its population worldwide. Moreover, such an effect was more pronounced in the three phytohormones that succeeded in breaking dormancy and growth of the Juniperus plant than in the other treatments.


Asunto(s)
Porcelana Dental , Juniperus , Aleaciones de Cerámica y Metal , Plantones , Titanio , Germinación , Reguladores del Crecimiento de las Plantas/farmacología , Cinetina/farmacología , Semillas , Hormonas
17.
BMC Complement Med Ther ; 24(1): 81, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336657

RESUMEN

BACKGROUND: Recent estimates indicate that a significant proportion of diabetic patients globally, up to 51%, are utilizing complementary and alternative medicine (CAM). To improve patient-provider communication and optimize prescribed treatments, healthcare professionals (HCPs) must understand the factors associated with CAM use among diabetic patients. There is a dearth of literature on HCPs perspectives on CAM use by diabetic patients. This study explored HCPs knowledge, perspective, and views on their diabetic patients' use of CAM. METHODS: Qualitative study using one-to-one semi-structured interviews conducted with 22 HCPs involved in the care of diabetic patients (6 endocrinologists, 4 general practitioners, 4 nurses and 8 pharmacists). Participants were recruited through general practices, community pharmacies and a diabetic centre in Saudi Arabia. Data were analyzed using thematic analysis. RESULTS: Five key themes resulted from the analysis. HCPs generally demonstrated negative perceptions toward CAM, particularly regarding their evidence-based effectiveness and safety. Participants described having limited interactions with diabetic patients regarding CAM use due to HCPs' lack of knowledge about CAM, limited consultation time and strict consultation protocols. Participants perceived convenience as the reason why patients use CAM. They believed many users lacked patience with prescribed medications to deliver favourable clinical outcomes and resorted to CAM use. CONCLUSIONS: HCPs have noted inadequate engagement with diabetic patients regarding CAM due to a lack of knowledge and resources. To ensure the safe use of CAM in diabetes and optimize prescribed treatment outcomes, one must address the communication gap by implementing a flexible consultation protocol and duration. Additionally, culturally sensitive, and evidence-based information should be available to HCPs and diabetic patients.


Asunto(s)
Terapias Complementarias , Diabetes Mellitus , Médicos Generales , Humanos , Diabetes Mellitus/terapia , Farmacéuticos , Actitud del Personal de Salud
19.
Cureus ; 15(4): e38254, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37261169

RESUMEN

Background Antibiotic overuse is a critical global health issue, and patient attitudes and expectations play a significant role in the inappropriate use of antibiotics. Limited research has been conducted on patient knowledge, attitudes, and perceptions of antibiotic use in Saudi Arabia. This survey aimed to assess patients' knowledge and attitudes related to antibiotic use in Jeddah, Saudi Arabia. Methods A cross-sectional survey using a convenience sampling method was conducted in Saudi Arabia. An online self-administered questionnaire was used to collect demographic data, antibiotic knowledge, and attitudes. Results The study included 400 patients, with a mean age of 39 years and an equal gender distribution (54% female). Most participants (75%) had not used antibiotics in the past year. Patients demonstrated moderate knowledge about antibiotics, with 81% recognizing that antibiotics can cause side effects and 69% knowing that overuse can lead to resistance. However, only 44% knew that antibiotics are not effective for all infections, and only half (50%) knew that antibiotics work against bacteria, not viruses. Patients held mixed attitudes toward antibiotic prescribing, with 25% believing it was essential to take antibiotics for every infection and 44% believing healthcare providers should prescribe antibiotics for respiratory tract infections. Logistic regression analyses showed that patient expectations for antibiotic prescribing were strongly associated with inappropriate antibiotic use. In contrast, patient satisfaction with antibiotic prescribing was negatively associated with inappropriate antibiotic use. Lower health literacy levels were also associated with inappropriate antibiotic use. Conclusion The study underscores the need for interventions that promote patient education and communication to ensure appropriate antibiotic use in primary care. Patient attitudes and beliefs, such as their expectations for antibiotic prescribing and health literacy levels, were identified as significant predictors of inappropriate antibiotic use.

20.
Cureus ; 15(4): e37592, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37193440

RESUMEN

Background Non-adherence to medication is a common problem in managing chronic diseases, which are a significant public health concern globally. This study aimed to identify factors related to medication adherence among patients with chronic diseases in Saudi Arabia. Methods A cross-sectional survey design was used to collect data through an online survey administered to 400 patients with chronic diseases residing in Jeddah between January and March 2023. The survey included questions about socio-demographic characteristics, chronic disease diagnosis, medication adherence, and factors that may influence medication adherence. Results This study recruited 400 participants and found that the majority were female, with a mean age of 46.2 years, and most had at least one chronic disease, with hypertension and diabetes being the most common. The medication adherence score for the entire sample was 5.4, indicating moderate adherence. Overall, 22.9% of study participants had poor adherence to medications. Factors associated with medication adherence included age, gender, and education level, with older age, female gender, and higher education being positively associated with adherence. Medication-related factors such as the number of medications prescribed, medication complexity, and medication cost were also found to be significantly associated with medication adherence. Conclusion Our study of medication adherence among chronic disease patients in Saudi Arabia found that adherence rates were moderate, with several factors significantly associated with better adherence. Specifically, older age, female gender, and higher education level were positively associated with better adherence, while a higher number of prescribed medications, more complex medication regimens, and higher medication costs were all significant predictors of poorer adherence.

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