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Psoriasis, a chronic inflammatory skin condition, and metabolic disorders, such as obesity, diabetes, and dyslipidemia, have long been recognized as distinct clinical entities. However, emerging evidence suggests a complex bidirectional relationship between these seemingly unrelated conditions. Psoriasis is characterized by an accelerated skin cell turnover, resulting in the formation of erythematous plaques with silvery scales. Metabolic disorders, on the other hand, encompass a range of conditions associated with abnormal metabolic processes, including insulin resistance, dyslipidemia, and chronic low-grade inflammation. It is intriguing to note that psoriasis is commonly associated with several metabolic comorbidities, with a higher prevalence observed in individuals with obesity, type 2 diabetes, and metabolic syndrome. Mounting evidence suggests that chronic inflammation plays a pivotal role in both psoriasis and metabolic disorders. Shared inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP), have been implicated in the pathogenesis of both conditions. Moreover, adipose tissue-derived hormones, known as adipokines, including leptin and adiponectin, exert modulatory effects on immune responses and may contribute to the link between psoriasis and metabolic abnormalities. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search across databases identified 16 eligible studies (1975-2023), totaling 6,623,379 participants. Inclusion criteria encompassed peer-reviewed observational studies focusing on adults and specified outcomes. Data extraction, quality assessment (Newcastle-Ottawa scale (NOS)), meta-analyses, and heterogeneity evaluations were conducted using rigorous methods. Psoriasis displayed a significant association with diabetes mellitus (DM, 18% increased incidence), hypertension (HTN, 35%), hyperlipidemia (19%), and obesity (25%). Substantial heterogeneity was observed in meta-analyses, particularly for DM. The NOS indicated varied study quality, with some studies categorized as a high or moderate risk of bias.
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Although psoriasis is a multi-organ disease, it is usually managed as a skin disease, ignoring its associated serious comorbidities. This meta-analysis aimed to investigate the relationship between psoriasis, dyslipidemia, and obesity. Two authors independently searched three databases (PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), The Cochrane Library, and Google Scholar). The search was set for articles published in the English language during the period from January 2013 to August 2023. The keywords "psoriasis", "hypercholesterolemia", "dyslipidemia", "low-density lipoproteins", "high body mass index", and "obesity", were used. Out of the 145 full texts reviewed, only seven studies fulfilled the inclusion and exclusion criteria (773,761 participants and 196,593 events). Psoriasis was associated with dyslipidemia and obesity (odds ratio (OR)=1.63, 95% CI: 1.42-1.88 and OR=1.70, 95% CI: 1.43-2.02), respectively, with significant heterogeneity (98% and 97%, respectively). Dyslipidemia and obesity were significant psoriasis comorbidities; a broader approach, viewing psoriasis as a multi-organ disease, is recommended for optimal treatment and outcomes.
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Background Low back pain (LBP) is common and considerably impacts daily lives across all age groups. MRI is not frequently used as a first-line investigation for patients presenting with LBP, except in the presence of red-flag symptoms. This study aimed to use pain severity and its impact as a predictor for MRI findings to help physicians decide whether a patient needs an MRI. Methods This cross-sectional study was conducted at the outpatient clinic of the neurosurgery department. The questionnaire included demographic data of the patients, red-flag symptoms, and the Dallas Pain Questionnaire (DPQ). The primary physician then determines whether the patient should have an MRI appointment. Results The study included 100 patients with LBP, of which 71 had chronic LBP (CLBP). Out of these 71, an MRI was requested for 62, but only 26 had findings related to LBP. Regarding the impact of CLBP on daily activities as measured by the DPQ, there was a significant association between those whose CLBP affected their daily activities and the decision to request an MRI. However, no significant statistical association was found between the three other parameters of the DPQ and the primary physician's decision to request an MRI. Conclusion Concerning the use of the DPQ questionnaire to predict MRI findings in patients with CLBP, the study indicates that significant pain impact on the DPQ does not necessarily correlate with MRI findings related to LBP. This suggests that the DPQ evaluation tool has no advantage over a physician's clinical judgment.
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Introduction Depression and anxiety are two types of mental disorders. Individuals with depression usually experience depressed mood, loss of interest or enjoyment, and reduced energy, leading to increased fatigability that diminishes their activity. Meanwhile, anxiety disorders refer to a group of mental disorders characterized by feelings of anxiety and fear. The coronavirus disease 2019 (COVID-19) pandemic has led to mass quarantine, isolation, and lockdowns worldwide, which have impacted the population's mental health. In Saudi Arabia, a study showed that 17.1% and 10.5% of the population had moderate-to-severe features of depression and anxiety, respectively. Demonstrating the prevalence of depression and anxiety in educational institutions is essential. This study aimed to measure the prevalence of depression and anxiety among students at Qassim University during the COVID-19 pandemic. Methods This cross-sectional study was conducted at Qassim University, Saudi Arabia. The students were selected using a multistage random sampling technique. An online questionnaire was sent to the selected students via e-mail and social media platforms. The questionnaire contained three parts: the first part included socio-demographic questions, the second part contained the Patient Health Questionnaire-9 (PHQ-9) to measure depression, and the third part contained the Generalized Anxiety Disorder-7 (GAD-7) questionnaire to measure anxiety. Results In total, 411 university students completed the questionnaire (response rate = 75%). The prevalence of depression and anxiety was 40.6% and 29.4%, respectively. Females had higher levels of depression and anxiety than men (p < 0.001). The College of Arabic Language and Social Studies (CALSS) had the highest prevalence of depression and anxiety (42.9% and 30.6%, respectively). Conclusion We found a high post-pandemic prevalence of depression and anxiety among the students at Qassim University. Our findings demonstrate the need for psychological intervention programs for the students of Qassim University.
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Cushing syndrome is a rare disease that rarely presents as acute psychosis. In this case, the patient presented with acute psychosis and agitation as the first manifestations of the disease which led to the admission of the patient to a psychiatry hospital for one month, as it was difficult to restrain her sufficiently for performing appropriate diagnostic tests due to disturbing behavior. She responded well to treatment with olanzapine and lorazepam to treat the patient's agitation, and successfully complete her evaluation. Thereafter, she was diagnosed with a pituitary tumor and underwent pituitary lesion resection via a microscopic transsphenoidal as needed. Two months after surgery, her cortisol levels returned to baseline, and she became calmer and decreased the tensity of her psychosis; however, it was only five months after surgery that her psychotic symptoms and disturbed behavior ceased.
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Purpose: Novel respiratory virus outbreaks are a recurring public health concern. Volunteering medical students can be a valuable asset during such times. This study investigated the willingness of medical students to volunteer during the coronavirus disease of 2019 (COVID-19) pandemic and the barriers to doing so, considering the possibility of exposure to COVID-19 and mode of contact. Patients and methods: This cross-sectional study was conducted using a self-administered online questionnaire adapted from the literature. The questionnaire comprised four parts: demographic variables, COVID-19-related variables, willingness scale, and barrier scale. The target population was medical students at four different colleges in Riyadh, Saudi Arabia. Results: A total of 802 students participated in the study. A small proportion of students (10.6%) were willing to participate in volunteering activities that could involve contact with patients with COVID-19 as compared to other settings (39.4-43.4%). More than one-quarter of students (26.8%) had risk factors for severe COVID-19. The main barrier to volunteering was the concern of transmitting the infection to family members (76.8%). Registration to receive the COVID-19 vaccine was positively associated with more willingness to volunteer (ß=0.17, p <0.001), whereas residing in a household with an elderly person was negatively associated (ß=-0.13, p <0.001). Female sex was positively associated with higher barrier score (ß=0.12, p <0.001). Conclusion: Medical students were more willing to volunteer in activities that did not involve direct contact with patients with COVID-19. A considerable proportion of participants had risk factors for severe illness. Sharing a household with an elderly person or child was associated with lower willingness to volunteer. Organizers of volunteering activities should offer various volunteering options considering the risk of infection; and be mindful of barriers to volunteering, especially risk factors for severe illness and eldercare and childcare responsibilities.
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Although sertraline is widely prescribed as relatively safe antidepressant drug, hepatic toxicity was reported in some patients with sertraline treatment. The present study was conducted to investigate the morphometric, hepatotoxicity, and change in gene expression of drug metabolizing enzymes. Male healthy adult rabbits (Oryctolagus cuniculus) ranging from 1050 to 1100â¯g were exposed to oral daily doses of sertraline (0, 1, 2, 4, 8â¯mg/kg) for 9 weeks. The animals were subjected to morphometric, hepatohistological, histochemical and quantitative real-time polymerase chain reaction analyses. Sertraline chronic exposure induced morphometric changes and provoked histological and histochemical alterations including: hepatocytes hydropic degeneration, necrosis, nuclear alteration, sinusoidal dilation, bile duct hyperplasia, inflammatory cells infiltration, portal vessel congestion, Kupffer cells hyperplasia, portal fibrosis and glycogen depletion. In addition, the gene expression of drug and arachidonic acid metabolizing enzymes were reduced significantly (p value <0.05). The most affected genes were cyp4a12, ephx2, cyp2d9 and cyp1a2, demonstrating 5 folds or more down-regulation. These findings suggest that chronic sertraline treatment induced toxic histological alterations in the hepatic tissues and reduced the gene expression of drug metabolizing enzymes. Patients on chronic sertraline treatment may be on risk of hepatotoxicity with reduced capacity to metabolize drugs and fatty acids.
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Antidepresivos/toxicidad , Hígado/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/toxicidad , Sertralina/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Crónica , Sistema Enzimático del Citocromo P-450/genética , Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 1/genética , Glucuronosiltransferasa/genética , Glucógeno/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Conejos , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patologíaRESUMEN
In this study, a novel inexpensive biosorbent of pine cone powder was used for the treatment of wastewater contaminated with phenol and chlorophenols (CPhs). The biosorbent was thoroughly characterized by using CHN and BET measurements, as well as FTIR, SEM, and XRD analyses. Kinetic and equilibrium biosorption experiments showed that the uptake was more than 80% within the first 30 min of contact time at pH 5.0. The biosorption of 4-CPh onto pine cone powder was higher than those of phenol and 2-CPh. The kinetic data were consistent with the pseudo-first-order kinetic model, and the Langmuir isotherm model best represented the equilibrium data. The maximum biosorption capacities of phenol, 2-CPh, and 4-CPh were 164.51, 189.44, and 220.12 mg/g, respectively, at 30 ± 1 °C. Therefore, the pine cone powder is an effective low-cost adsorbent for the removal of phenol and CPhs from the contaminated water.
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Fenoles/aislamiento & purificación , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Biomasa , Clorofenoles/química , Clorofenoles/aislamiento & purificación , Concentración de Iones de Hidrógeno , Cinética , Microscopía Electrónica de Rastreo , Fenoles/química , Pinus/química , Polvos , Soluciones , Espectroscopía Infrarroja por Transformada de Fourier , Eliminación de Residuos Líquidos/instrumentación , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Difracción de Rayos XRESUMEN
Most industrial waste discharges are often contaminated with phenolic compounds, which constitute a major source of water pollution owing to their toxicity and low biodegradability. Development of cost-effective treatment of such industrial wastewater is therefore of paramount importance. Towards this end, we explore the efficacy of Pine bark powder (PBP), which is an agricultural solid waste material, as a low-cost biosorbent without any pre-treatment, for the adsorptive removal of 2,4,6-trichlorophenol (2,4,6-TCP) from aqueous media. The PBP was thoroughly characterized and the effect of important adsorption parameters were examined in the present investigation. The batch equilibrium data were analyzed using well-known isotherm models. Freundlich isotherm model provided the best description of the equilibrium biosorption behavior. At 25 ± 1 °C, the maximum biosorption capacity (qmax) was 289.09 mg/g, which is higher than most biosorbents reported in the literature while the removal as high as 97% was obtained. Moreover, the biosorption process was fast, attaining equilibrium in less than 120 min of contact. The Elovich model accurately described the kinetics data. In view of high biosorption capacity and.
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Methotrexate (MTX) is widely used in the treatment of some forms of cancer but having severe side effects. The present work aimed to investigate the protective role of propolis treatment against alterations induced by MTX on the hepatic and renal tissues. Rabbits were exposed to MTX (0.25 mg/kg), with or without propolis (50 mg/kg) while hepatic and renal biopsies were examined for histological and histochemical abnormalities. Methotrexate induced hydropic degeneration, pyknosis, sinusoidal dilatation and bile duct hyperplasia in the liver together with renal tubular degeneration, glomerular shrinkage and hyaline droplet precipitation. While propolis partially ameliorated some of the morphometric and biochemical alterations, none of the hepatic alterations induced by MTX was protected by propolis treatment. Nevertheless glomerular shrinkage and renal tubule degeneration were partially protected in animals received both MTX plus propolis. It is concluded that propolis treatment has little or no ameliorative effect in protecting the hepatic and renal tissues from MTX toxicity.
El metotrexato (MTX) es ampliamente utilizado en el tratamiento de algunas formas de cáncer, pero tiene efectos secundarios graves. El presente trabajo tuvo como objetivo investigar el papel protector del tratamiento con própoleo frente a las alteraciones inducidas por el MTX en los tejidos hepático y renal. Se expusieron conejos a MTX (0,25 mg / kg), en grupos con y sin propóleo (50 mg / kg), y se realizaron biopsias hepáticas y renales, que fueron examinadas buscando anomalías histológicas e histoquímicas. El metotrexato indujo la degeneración hidrópica, picnosis, dilatación sinusoidal e hiperplasia del conducto biliar en el hígado, junto con la degeneración tubular renal, la contracción glomerular y la precipitación hialina. Mientras que el propóleo parcialmente mejoró algunas de las alteraciones morfométricas y bioquímicas, ninguna de las alteraciones hepáticas inducidas por MTX fue protegido por el tratamiento con propóleo. Sin embargo, la contracción glomerular y la degeneración de los túbulos renales fueron parcialmente protegidos en animales que recibieron MTX más propóleo. Se concluye que el tratamiento con propóleo tiene poco o ningún efecto mejorador en la protección de los tejidos hepáticos y renales sometidos a la toxicidad de MTX.
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Animales , Masculino , Conejos , Própolis/administración & dosificación , Metotrexato/toxicidad , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Peso Corporal , Modelos Animales de Enfermedad , Riñón/patología , Hígado/patologíaRESUMEN
Zinc oxide nanoparticles (ZnO NPs) are widely used in industry and cosmetic products with promising investment in medical diagnosis and treatment. However, these particles may reveal a high potential risk for human health with no information about hepatotoxicity that might be associated with their exposure. The present work was carried out to investigate the histological and histochemical alterations induced in the hepatic tissues by naked 35nm ZnO NPs. Male Wistar albino rats were exposed to ZnO NPs at a daily dose of 2mg/kg for 21days. Liver biopsies from all rats under study were subjected to histopathological examinations. In comparison with the control rats, the following histological and histochemical alterations were demonstrated in the hepatic tissues of rats exposed to ZnO NPs: sinusoidal dilatation, Kupffer cells hyperplasia, lobular and portal triads inflammatory cells infiltration, necrosis, hydropic degeneration, hepatocytes apoptosis, anisokaryosis, karyolysis, nuclear membrane irregularity, glycogen content depletion and hemosidrosis. The findings of the present work might indicate that ZnO NPs have potential oxidative stress in the hepatic tissues that may affect the function of the liver. More work is needed to elucidate the toxicity and pathogenesis of zinc oxide nanoparticles on the vital organs.
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Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Glucógeno/metabolismo , Hígado/efectos de los fármacos , Nanopartículas/toxicidad , Óxido de Zinc/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hemosiderosis/inducido químicamente , Hemosiderosis/metabolismo , Hemosiderosis/patología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Macrófagos del Hígado/efectos de los fármacos , Macrófagos del Hígado/metabolismo , Macrófagos del Hígado/patología , Hígado/metabolismo , Hígado/patología , Masculino , Nanopartículas/química , Necrosis , Tamaño de la Partícula , Ratas Wistar , Propiedades de Superficie , Óxido de Zinc/químicaRESUMEN
Roflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory cells are neutrophils. Thus, roflumilast has a potential off-label use in the treatment of asthma. This study was designed to evaluate the effects of co-inhalation of roflumilast and fluticasone compared to that of formoterol and fluticasone in ovalbumin-sensitized and-challenged BALB/c mice. Besides normal control group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n = 8): positive control, vehicle-treated, and five drug-treated groups. Treatments (µg/kg) were given as 15 min-inhalation once/day for five days as follows: roflumilast (500), formoterol (50), fluticasone (1000), roflumilast + fluticasone (500 + 1000), and formoterol + fluticasone (50 + 1000). Penh values were measured in conscious unrestrained mice using the single-chamber whole-body plethysmography. Airway hyperreactivity to inhaled methacholine was evaluated. Bronchoalveolar lavage fluid was used for the measurements of levels of IL-4, IL-5, TNF-α, OVA-specific IgE, and total and differential white cells. Lung sections were stained with hematoxylin and eosin and periodic acid-Schiff. The asthmatic mice showed significant increases in airway hyperreactivity which were significantly reversed by the combination treatments. The asthmatic mice showed significant increases in levels of IL-4, IL-5, TNF-α, ovalbumin-specific IgE, and total and differential white cells in bronchoalveolar lavage fluid. All treatments (except formoterol) significantly reversed these changes mainly with roflumilast + fluticasone. The asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were maximally reversed by roflumilast + fluticasone, while minimally reversed by formoterol. In conclusion, co-inhalation of roflumilast + fluticasone more significantly improved inflammation and histopathological changes than co-inhalation of formoterol + fluticasone in ovalumin-asthmatic mice. Further studies are needed to help confirm the potential off-label add-on use of roflumilast in typical and atypical asthma and asthma-chronic obstructive pulmonary disease overlap syndrome. Impact statement Roflumilast, a selective phosphodiesterase-4 inhibitor, was approved for the treatment of chronic obstructive pulmonary disease (COPD). This study showed that co-inhalation of roflumilast and fluticasone significantly decreased airway hyperresponsiveness in ovalumin-asthmatic mice. Also, it more significantly improved inflammation and histopathological changes than co-inhalation of formoterol and fluticasone. The current results showed that inhaled roflumilast reduced counts of eosinophils, neutrophils, and macrophages in bronchoalveolar lavage fluid. Consequently, inhaled roflumilast might be of potential off-label benefit in treatment of eosinophilic and neutrophilic asthma and asthma-COPD overlap syndrome (ACOS). These results could also support other experimental and clinical studies addressing the same issue.
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Aminopiridinas/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Benzamidas/uso terapéutico , Fluticasona/uso terapéutico , Fumarato de Formoterol/uso terapéutico , Administración por Inhalación , Aminopiridinas/administración & dosificación , Animales , Antiasmáticos/administración & dosificación , Benzamidas/administración & dosificación , Líquido del Lavado Bronquioalveolar/química , Ciclopropanos/administración & dosificación , Ciclopropanos/uso terapéutico , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Fluticasona/administración & dosificación , Fumarato de Formoterol/administración & dosificación , Inmunoglobulina E/análisis , Interleucina-4/análisis , Interleucina-5/análisis , Ratones , Ratones Endogámicos BALB C , Factor de Necrosis Tumoral alfa/análisisAsunto(s)
Derivación Gástrica/efectos adversos , Hiperemesis Gravídica/diagnóstico , Obesidad Mórbida/cirugía , Deficiencia de Tiamina/diagnóstico , Encefalopatía de Wernicke/etiología , Anastomosis en-Y de Roux/efectos adversos , Anastomosis en-Y de Roux/métodos , Dilatación y Legrado Uterino/métodos , Femenino , Derivación Gástrica/métodos , Edad Gestacional , Humanos , Hiperemesis Gravídica/complicaciones , Obesidad Mórbida/complicaciones , Obesidad Mórbida/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Embarazo , Enfermedades Raras , Medición de Riesgo , Deficiencia de Tiamina/complicaciones , Deficiencia de Tiamina/tratamiento farmacológico , Resultado del Tratamiento , Encefalopatía de Wernicke/fisiopatología , Encefalopatía de Wernicke/terapia , Adulto JovenRESUMEN
The pro-inflammatory context of sickle cell disease promotes the liberation of cytokines such as CCL5, encoded by a gene located on chromosome 17. Herein, the occurrence of three variations of CCL5 in sickle cell anemia (SCA) and their relations to two major complications - painful crisis and presence of infections - were investigated. 100 SCA Tunisian patients and 100 healthy subjects were included in the case control study. Then the sample of patients was divided into two groups according to the presence or absence of each complication. The polymorphisms, namely g.-403G>A, g.-28C>G and g.In1.+1T>C, were analyzed by PCR/sequencing. Our findings show the presence of eight genotypes, namely GG, GA and AA of g.-403G>A, CC, CG and GG of g.-28C>G, and TT and TC of g.In1.+1T>C. The frequencies of studied single nucleotide polymorphisms (SNPs) and haplotypes in SCA patients do not differ significantly from healthy control group results. There is also no significant association between the analyzed polymorphisms and complications as for painful crisis and presence of infections (p > 0.05). Altogether, our data support the conclusion that the three polymorphisms of CCL5, namely g.-403G>A, g.-28C>G and g.In1.+1T>C, do not seem to be involved in the clinical variability of SCA in Tunisia.
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Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Quimiocina CCL5/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Fenotipo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TúnezRESUMEN
OBJECTIVES: To determine the incidence, diversity of adverse drug reactions (ADRs), and impact of pharmacovigilance on reporting it. METHODS: This prospective and retrospective study was carried out in the Department of Medicine, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between January to December 2011 in 600 patients of ADR. Data regarding age and gender distribution of the patients, incidence rate, drugs, body systems/organs involved in ADR, time of occurrence of adverse drug reactions, total number of drugs administered, and impact of pharmacovigilance on finding the incidence rate of ADR were recorded. Comparison of the 2 data was carried out to determine the impact of pharmacovigilance. RESULTS: Incidence rate of ADRs in retrospective study was 3.1% and 5.5% in the prospective study. The highest incidence of ADR (retrospective 15% and prospective 14.5%) was observed in both groups in patients receiving more than 10 drugs. The frequency of ADR in relation to age in both groups was highest in patients of age >60 years; it was 52.7% in retrospective study and 54.5% in prospective study. Antibiotics were the more frequently involved in ADR, (48.5% in prospective study and 36.9% in retrospective study). The system most commonly involved in ADR was gastrointestinal tract 47.4% in retrospective study and 57.6% in prospective study. None of the ADR proved to be fatal. CONCLUSION: Low incidence of hospitalized ADR in our study (5.5%) is due to lack of awareness in healthcare professionals in reporting ADR. Undoubtedly, pharmacovigilance brought more patients with ADR to record.
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Erupciones por Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Enfermedades Gastrointestinales/epidemiología , Hospitales de Enseñanza , Farmacovigilancia , Enfermedades Respiratorias/epidemiología , Gestión de Riesgos/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Antibacterianos/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Fármacos Cardiovasculares/efectos adversos , Diuréticos/efectos adversos , Erupciones por Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Glucocorticoides/efectos adversos , Humanos , Incidencia , Medicina Interna , Masculino , Persona de Mediana Edad , Polifarmacia , Estudios Prospectivos , Enfermedades Respiratorias/inducido químicamente , Estudios Retrospectivos , Arabia Saudita/epidemiología , Distribución por Sexo , Adulto JovenRESUMEN
This study describes the interaction between human acetylcholinesterase (AChE), a key regulator of central and peripheral cholinergic function, and the widely used nitrogen mustard alkylating agent, cyclophosphamide (CP). Modeling of the AChE sequence (NCBI Accession No: AAI05061.1) was performed using 'Swiss Model Workspace'. The protein-model was submitted to the Protein Model Database and was assigned accession number PM0077393. A plot showing normalized QMEAN scores versus protein size was made to compare the model with a non-redundant set of Protein Data Bank structures, which gave a Z-score QMEAN as -0.58. The predicted local error for the modeled structure was found to be well within tolerable limits. Z-score values for Cß interaction, all atom interaction, solvation and torsion were found to be -1.10, -0.90, -0.06 and -0.40, respectively. Docking between CP and AChE was performed using 'Autodock4.2'. Apart from other interaction-types, six carbon atoms of CP (C1, C2, C3, C4, C6 and C7) were determined to be involved in hydrophobic interactions with amino acid residues Y121, W233, L323, F331, F335 and Y338 of the 'acyl pocket' within AChE. Five carbon atoms of CP (C2, C4, C5, C6 and C7) were involved in hydrophobic interactions with 3 amino acid residues within the enzyme's 'catalytic site'. In conclusion, hydrophobic interactions play a major role in the appropriate positioning of CP within the 'acyl pocket' as well as 'catalytic site' of AChE to permit suitable orientation and allow docking. This information may aid the design of more potent and versatile AChE-inhibitors as pharmacologic tools and drugs to characterize and treat neurological disorders, and additionally provides a model whose value can be quantitatively assessed by X-ray crystallographic analysis of the AChECP three-dimensional structure.
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Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Encéfalo/enzimología , Ciclofosfamida/química , Ciclofosfamida/metabolismo , Modelos Moleculares , Sitios de Unión/fisiología , Cristalografía por Rayos X , Bases de Datos de Proteínas , Humanos , Unión Proteica/fisiología , Distribución AleatoriaRESUMEN
The antihyperglycaemic and hypolipidaemic effects of the methanolic extract of Caralluma tuberculata were investigated in streptozotocin (STZ)-induced diabetic rats. The antihyperglycaemic activity was assessed by the reduction in fasting blood glucose (54% at 4th week) and the peak of blood glucose at 120?min of an oral glucose tolerance test in diabetic rats. Further, the tested extract also increased plasma insulin by 206.8%. The hypolipidaemic action of the extract was evident by the significant decrease in the levels of total cholesterol, triglycerides and LDL-cholesterol by 41.5%, 36.7% and 49.1%, respectively, compared to diabetic rat values. Interestingly, the extract increased the cardio-protective lipid HDL-cholesterol by 147.97% as compared to diabetic rat value. The present data suggests that the methanolic extract of C. tuberculata has both antihyperglycaemic and hypolipidaemic effects in STZ-induced diabetic rats that may need further studies to be used in the management of diabetes and associated hyperlipedaemia.
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Apocynaceae/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Fitoterapia/métodos , Extractos Vegetales/farmacología , Análisis de Varianza , Animales , Glucemia/análisis , Colesterol/sangre , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/análisis , Hipolipemiantes/análisis , Insulina/sangre , Metanol , Extractos Vegetales/análisis , Ratas , Triglicéridos/sangreRESUMEN
Marrubium vulgare and Withania somnifera are used in folk medicine of several countries. Many researches showed that they are used for the treatment of variety of diseases due to their antioxidant effects. The present aim of this study was to evaluate the antihepatotoxic and antioxidant activities of the both extracts against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Both extracts were given orally in a dose of 500 mg/kg/day for 4 weeks along with CCl4 started at the 7th week of induction of hepatotoxicity. The antihepatotoxic activity was assessed by measuring aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH), tissue content and malondialdehyde (MDA) as well as histopathological examination. Both extracts showed a significant antihepatotoxic effect by reducing significantly the levels of AST, ALT and LDH. However, ALP levels were decreased non-significantly. Regarding the antioxidant activity, they exhibited significant effects by increasing the GPx, GR and GST activities with increased GSH tissue contents and decreased production of MDA level. Furthermore, both extracts alleviated histopathological changes in rats' liver treated with CCl4. M. vulgare and W. somnifera protect the rats' liver against CCl4-induced hepatotoxicity. This effect may be attributed, at least in part, to the antioxidant activities of these extracts.
RESUMEN
The Glucose-6-phosphate dehydrogenase (G6PI) deficiency is the most common enzymopathy worldwide. WHO had classified Tunisia among countries that are moderately affected by this affection. However, no mass-screening reflecting the real incidence was realized. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis in Tunisia. A total of 1102 neonates, born in CMNT center of Maternity and of Neonatology of Tunis during the going periods from April, 2005 till May, 2005 and from June, 2006 till September, 2006, have been enclosed in the study. The samplings included 953peripheral venous blood and 149 blood cordon. Among 1102 samplings, only 976 were of use to the screening. In our mass-screening, we consider all newborns that were born in the CMNT during the period of study and were included in the screening. A dosage of the enzymatic activity was realized using spectrophotometric method. G6PD electrophoresis and molecular study by PCR/RFLP were realized for the overdrawn newborn children. Among 976 screening neonates, 43 individuals (4.4%) were found to be G6PD deficient by quantitative enzyme assay. Newborn affected were distributed in 23 boys and 20 girls (sex ratio of 1.15). The electrophoretic mobility and the molecular biology were realized for the affected newborn. Molecular characterization of 30 G6PD deficient neonates revealed that the G6PD A- was the most common and was detected in 20 of 43 individuals (66.7%), followed by G6PD Mediterranean that was detected in 6 (13.3%). At least, 4 other unknown mutations were not able to be determined by PCR/RFLP (n=4). In conclusion G6PD deficiency is frequent in our country, justifying a systematic neonatal screening, to avoid the arisen of grave consequences of this affection. The African variant is the most frequent in our country followed by the Mediterranean one.
Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Tamizaje Neonatal , Femenino , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , TúnezRESUMEN
BACKGROUND: In Gaucher disease, the infiltration of the bone marrow by glucocerebroside-laden macrophages (Gaucher cells) triggers a diverse pattern of skeletal disease that results in crippling complications. Reliable ascertainment of the severity and pattern of skeletal disease is essential to determine disease status and the response to enzyme replacement therapy (ERT). Although there is ample documentation of reversal of haematological and visceral disease by ERT, there is a paucity of data on skeletal response to ERT in children. AIM: To delineate the pattern of bone disease in children with Gaucher disease in Egypt and to evaluate its response to ERT. METHOD: Twenty-two children with Gaucher disease were treated with ERT. Phenotyping by clinical, laboratory and radiological criteria was performed at baseline and following 11.2 +/- 4 months of ERT. Genotyping for glucocerebrosidase (GBA) mutations was performed by gene sequencing, and genotype-phenotype correlations were performed.Results. Two-thirds of the patients were from consanguineous pedigrees and 14/22 patients were homozygous or compound heterozygous for L444P and D409H mutations. Bone involvement was detected by plain radiology in 11 children (50%) and in 16 (73%) by magnetic resonance imaging (MRI). There was no correlation of severity of bone involvement and GBA genotype. ERT ameliorated bone disease: 10 of the 11 children with abnormal radiographic findings at baseline showed improvement in skeletal lesions; while 9/16 showed improvement of marrow disease by MRI. Radiographic sensitivity and specificity were 62% and 82% compared to MRI for detection of bone involvement in this patient population. At baseline, bone pain was present in 5 patients and ERT resulted in complete symptomatic remission in all of them. ERT was associated with significant improvement in growth parameters and amelioration of haematological and visceral involvement. CONCLUSION: Symptomatic and radiological skeletal disease is common in children with Gaucher disease in Egypt. MRI is the most accurate technique for detecting early skeletal involvement. There was no correlation between severity of skeletal involvement and GBA genotype. ERT was effective in ameliorating radiological manifestations of skeletal disease and achieving complete remission of bone pain.