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1.
Comput Methods Programs Biomed ; 232: 107443, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36889249

RESUMO

BACKGROUND AND OBJECTIVE: Besides efforts on vaccine discovery, robust and intuitive government policies could also significantly influence the pandemic state. However, such policies require realistic virus spread models, and the major works on COVID-19 to date have been only case-specific and use deterministic models. Additionally, when a disease affects large portions of the population, countries develop extensive infrastructures to contain the condition that should adapt continuously and extend the healthcare system's capabilities. An accurate mathematical model that reasonably addresses these complex treatment/population dynamics and their corresponding environmental uncertainties is necessary for making appropriate and robust strategic decisions. METHODS: Here, we propose an interval type-2 fuzzy stochastic modeling and control strategy to deal with the realistic uncertainties of pandemics and manage the size of the infected population. For this purpose, we first modify a previously established COVID-19 model with definite parameters to a Stochastic SEIAR (S2EIAR) approach with uncertain parameters and variables. Next, we propose to use normalized inputs, rather than the usual parameter settings in the previous case-specific studies, hence offering a more generalized control structure. Furthermore, we examine the proposed genetic algorithm-optimized fuzzy system in two scenarios. The first scenario aims to keep infected cases below a certain threshold, while the second addresses the changing healthcare capacities. Finally, we examine the proposed controller on stochasticity and disturbance in parameters, population sizes, social distance, and vaccination rate. RESULTS: The results show the robustness and efficiency of the proposed method in the presence of up to 1% noise and 50% disturbance in tracking the desired size of the infected population. The proposed method is compared to Proportional Derivative (PD), Proportional Integral Derivative (PID), and type-1 fuzzy controllers. In the first scenario, both fuzzy controllers perform more smoothly despite PD and PID controllers reaching a lower mean squared error (MSE). Meanwhile, the proposed controller outperforms PD, PID, and the type-1 fuzzy controller for the MSE and decision policies for the second scenario. CONCLUSIONS: The proposed approach explains how we should decide on social distancing and vaccination rate policies during pandemics against the prevalent uncertainties in disease detection and reporting.


Assuntos
Algoritmos , COVID-19 , Humanos , Lógica Fuzzy , Simulação por Computador , Distanciamento Físico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação
2.
Hum Exp Toxicol ; 41: 9603271221133538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36321261

RESUMO

Styrene is widely used in industrial applications. Inhalation exposure occurs in the industry. Some studies indicated that serum prolactin concentrations increased after exposure to styrene, while other studies found no change. In this systematic review, the search was done with the keywords styrene and prolactin in the PubMed, Science Direct, Web of Science and Scopus databases, regardless of the publication period. 118 studies were obtained and only seven articles were finally selected according to exclusion and inclusion criteria. The effect of styrene on prolactin secretion was selected in both human and animal studies. The increased response was seen in inhalation exposures. Subcutaneous exposure has no significant effect on prolactin levels. The observed responses were both dose-dependent and gender-dependent. Changes in serum prolactin were more frequent in women compared to exposed men. Dopamine depletion was not observed in all studies, so more tests on laboratory animals are necessary to clarify the possible mechanism.


Assuntos
Prolactina , Estireno , Animais , Masculino , Humanos , Feminino , Dopamina , Exposição por Inalação
3.
J Fr Ophtalmol ; 45(3): 338-343, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35063294

RESUMO

PURPOSE: To compare fluorescein angiography (FA) and indocyanine green angiography (ICGA) for imaging of central serous chorioretinopathy (CSC) patients. METHODS: The observational cross-sectional clinical study was conducted on 131 eyes of 131 patients with CSC who were candidates for photodynamic therapy (PDT). An experienced ophthalmologist marked the leakage sites and choroidal hyperpermeability sites that needed PDT. For each eye, simultaneous FA and ICGA imaging with the maximum leakage area was selected for comparison regarding the site and size. RESULTS: The mean±standard deviation age of patients was 44.53±9.03 years. Of 226 leakage points, 177 (78.32%) points were in the same site, and 168 (74.34%) points were in the same size on FA. No statistical difference was found between age (P=0.45), sex (P=0.32), and chronicity (P=0.11) of the disease in comparing the ICGA images to the FA images regarding leakage at the same site. A statistically significant difference was also found regarding size of leakage and chronicity (P<0.001). CONCLUSION: The current results suggested that FA could be considered an alternative ocular imaging technology as a guide for PDT in CSC patients.


Assuntos
Coriorretinopatia Serosa Central , Fotoquimioterapia , Adulto , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/tratamento farmacológico , Corantes , Estudos Transversais , Angiofluoresceinografia/métodos , Humanos , Verde de Indocianina , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual
4.
Anim Genet ; 50(5): 460-474, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31355950

RESUMO

RNA editing is a post-transcription maturation process that diversifies genomically encoded information and can lead to transcriptome diversity. Thanks to next-generation sequencing technologies, a large number of editing sites have been identified in different species. Although this mechanism is well described in mammals, only a few studies have been performed in chicken. Here, candidate or potential RNA editing sites were identified in eight different tissues of chicken (brain, spleen, colon, lung, kidney, heart, testes and liver). We identified 68 A-to-G editing sites in 46 genes. Only two of these were previously reported in chicken. We found no C-to-T sites, attesting to the lack of this type of editing mechanism in chicken. Similar to mammals, the editing sites were enriched in non-coding regions, rarely resulted in a change in amino acids, showed a critical role in the nervous system and had a low guanosine level upstream of the editing site and some enrichment downstream from the site. Moreover, in contrast to mammals, editing sites were weakly enriched in interspersed repeats and the number and editing ratio of non-synonymous sites were higher than for those of synonymous sites. Interestingly, we found several tissue-specific edited genes, including GABRA3, SORL1 and HTR1D in brain and RYR2 and FHOD3 in heart, that were associated with functional processes relevant to the corresponding tissue. This finding highlights the importance of RNA editing in several chicken tissues, especially the brain, and establishes a foundation for further exploration of this process.


Assuntos
Galinhas/genética , Especificidade de Órgãos , Edição de RNA , Animais , Transcriptoma
5.
Animal ; 12(6): 1196-1207, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29282162

RESUMO

Negative energy balance (NEB) is an altered metabolic state in modern high-yielding dairy cows. This metabolic state occurs in the early postpartum period when energy demands for milk production and maintenance exceed that of energy intake. Negative energy balance or poor adaptation to this metabolic state has important effects on the liver and can lead to metabolic disorders and reduced fertility. The roles of regulatory factors, including transcription factors (TFs) and micro RNAs (miRNAs) have often been separately studied for evaluating of NEB. However, adaptive response to NEB is controlled by complex gene networks and still not fully understood. In this study, we aimed to discover the integrated gene regulatory networks involved in NEB development in liver tissue. We downloaded data sets including mRNA and miRNA expression profiles related to three and four cows with severe and moderate NEB, respectively. Our method integrated two independent types of information: module inference network by TFs, miRNAs and mRNA expression profiles (RNA-seq data) and computational target predictions. In total, 176 modules were predicted by using gene expression data and 64 miRNAs and 63 TFs were assigned to these modules. By using our integrated computational approach, we identified 13 TF-module and 19 miRNA-module interactions. Most of these modules were associated with liver metabolic processes as well as immune and stress responses, which might play crucial roles in NEB development. Literature survey results also showed that several regulators and gene targets have already been characterized as important factors in liver metabolic processes. These results provided novel insights into regulatory mechanisms at the TF and miRNA levels during NEB. In addition, the method described in this study seems to be applicable to construct integrated regulatory networks for different diseases or disorders.


Assuntos
Bovinos , Metabolismo Energético , Redes Reguladoras de Genes , MicroRNAs , Animais , Bovinos/fisiologia , Feminino , MicroRNAs/metabolismo , Período Pós-Parto , RNA Mensageiro
6.
Ann Burns Fire Disasters ; 31(3): 204-208, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30863254

RESUMO

Wound care quality and speed of burn healing are important factors that affect the treatment, prognosis and complications of burns. Burn care is challenging, and the ideal method controversial. The aim of this study was to compare the effects of a new dressing (ColActive dressing) in the treatment of superficial second-degree burns versus traditional dressing including Vaseline and Nitrofurazone. This was a randomized clinical trial study involving 25 cases. A superficial second-degree burn area was divided into two parts in each patient; randomly, traditional dressing was used on one area, and ColActive plus Ag dressing on the other. Every 3 days, after removing the dressings and washing the wounds, wound surface area was evaluated by medical photographic records and J image software. Wound surface area in the two groups was compared before dressing and on the 3rd, 6th, 9th and 12th day afterwards. The difference was not significant before dressing, but significant on the 3rd, 6th, 9th and 12th post-operative day. The difference was significant in both groups, but it was more prominent in the ColActive group (p<0.001) than in the traditional group (p<0.05). Considering the results of this study and good results in previous case reports, ColActive may be more effective than traditional dressing. We suggest a more comprehensive study for a longer period with a larger number of cases to compare other important variables such as scar quality, cost, and pain in the two dressings.


La qualité des soins locaux et la vitesse de cicatrisation sont d'importants paramètres affectant le traitement, le pronostic et les complications des brûlures. La méthode idéale reste encore à trouver. Le but de cet étude est de comparer un nouveau pansement (ColActive ®) au traditionnel nitrofurazone/vaseline sur les brûlures du 2ème superficiel. Il s'agit d'une étude randomisée portant sur 25 patients. Les zones de 2ème superficiel étaient divisées en 2 recevant, après tirage au sort, l'une ColActive® Plus Ag, l'autre nitrofurazone/vaseline. Après nettoyage, les photographies des brûlures étaient évaluées en utilisant Image J, à l'entrée et à J3, 6, 9 et 12. Les différences étaient significatives à J3, 6, 9, 12 avec une valeur de p plus prononcée (<0,001) dans le groupe ColActive® Plus Ag que dans le groupe contrôle (<0,05). Considérant ces résultats en faveur de l'utilisation de ColActive® Plus Ag, nous suggérons une étude plus globale, sur un nombre plus élevé de patients, comparant aussi la qualité cicatricielle, le coût et la douleur.

7.
Artigo em Inglês | MEDLINE | ID: mdl-28904802

RESUMO

BACKGROUND: Ramsar, a city of Iran located on the coast of the Caspian Sea, has been considered to be enormously important due to its high natural radioactivity levels. People living in High Level Natural Radiation Areas (HLNRAs) have been exposed by several sources, one of which could be foodstuff. However, many studies have been carried out to measure the environmental radioactivity in Ramsar, but no survey has been conducted in all stapled consumed foods yet. This study was dedicated to determine 226Ra activity concentration in the daily diets of Ramsar residents as a probable exposure. METHODS: Approximately 70 different market samples were collected during the four seasons based on the daily consumption patterns of residents which have the highest consumption and their availability in the seasons. All samples, after washing, drying and pretreatment, were analyzed for 226Ra radionuclide determination by α-spectrometry. RESULTS: The mean radioactivity concentration of 226Ra ranged between 7 ± 1 mBq Kg-1 wet weight in meat, and 318 ± 118 mBq Kg-1 for tea dry leaves. The 226Ra activity concentrations in collected samples varied from below the minimum detectable activity up to 530 ± 30 mBq Kg-1. To compare the results with United Nations Scientific Committee on Effects of Atomic Radiation (UNSCEAR) reference values, the 226Ra activity concentrations concluded from the results appear to be higher in milk, chicken and eggs and less in grain products, vegetables, fruits and fish products. These results indicate that no significant 226Ra contamination is present in market foodstuffs and provide reference values for the foodstuffs in Ramsar. CONCLUSIONS: Of the total daily dietary 226Ra exposure from market consuming foodstuffs for adults in Ramsar, the largest percentage was from wheat. The residents consuming wheat and manufacturing wheat products such as bread, pasta, porridge, crackers, biscuits, pancakes, pies, pastries, cakes, cookies, muffins, rolls, doughnuts, breakfast cereals and so on may receive an elevated dose in the diet. In conclusion, with regards to presence of 226Ra in foodstuffs it is necessary to monitor regularly the activity of 226Ra in foodstuffs including market and local foods.

8.
Int Nurs Rev ; 62(4): 584-92, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26572823

RESUMO

AIM: This study aimed to explore the perception of Iranian nurses concerning spiritual care and to reveal any confronted barriers. BACKGROUND: Although the context of spiritual care is a substantial aspect of holistic care, the delivery of spiritual care has been problematic due to lack of nurses' understanding of this concept. INTRODUCTION: Nurses' perceptions of spirituality and spiritual care directly influence their performance as well as their relationships with patients. METHODS: This cross-sectional survey was conducted in 2013 with 259 nurses working in hospitals affiliated with Qazvin University of Medical Sciences, Iran. Data were collected using the Spirituality and Spiritual Care Rating Scale alongside qualitative open-ended questions. Descriptive and inferential statistics were used for the quantitative data and content analysis for the qualitative data. RESULTS: The overall average for spirituality and spiritual care was 2.84 (score range: 1-4), indicating a moderate mean score. A significant relationship was found between education level and spiritual care. The majority of participants believed that they did not receive enough training in this aspect of care. The main obstacles regarding delivering spiritual care included busy working schedules, insufficient knowledge regarding spiritual care, low motivation, diversity of patients' spiritual needs and feeling 'unqualified' to provide spiritual cares. DISCUSSION: Consistent with the previous studies, this study has demonstrated that nurses had low confidence to meet the spiritual needs of patients due to lack of knowledge and training in this regard. CONCLUSION: Iranian nurses' perception of spirituality and spiritual care is moderate, reflecting that they do not receive sufficient training regarding spiritual care. IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY: Despite the attention focused on spiritual care in clinical settings in Iran, there remains a significant gap in terms of meeting the spiritual needs of patients in nursing practice. This finding assists nursing clinicians, educators and policy makers to more effectively approach spiritual care as a beneficial component of holistic care. It is proposed that more emphasis is placed on integrating spirituality content into educational programmes to enable more effective clinical delivery. In addition, it would be beneficial to implement more widespread cultural assessment in order to further benefit spiritual care practices.


Assuntos
Atitude do Pessoal de Saúde , Padrões de Prática em Enfermagem , Terapias Espirituais , Espiritualidade , Adulto , Competência Clínica , Estudos Transversais , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar , Autoimagem , Fatores Socioeconômicos , Adulto Jovem
9.
East Mediterr Health J ; 21(2): 100-10, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25876821

RESUMO

This study explored the perceived value, role and reported use of clinical guidelines by clinicians in urban paediatric and maternity hospital settings, and the effect of current implementation strategies on clinician attitudes, knowledge and behaviour. A total of 63 clinicians from 7 paediatric and maternity hospitals in Kabul, Afghanistan participated in structured focus groups; content analysis methodology was used for identification and analysis of key themes. Seven sets of guidelines, protocols or standards were identified (including 5 WHO-endorsed guidelines). However, most are failing to achieve high levels of use. Factors associated with guideline use included: clinician involvement in guideline development; multidisciplinary training; demonstrable results; and positive clinician perceptions regarding guideline quality and contextual appropriateness. Implementation activities should fulfil 3 major objectives: promote guideline awareness and access; stimulate motivation among clinical guideline users; and actively facilitate adherence to guidelines.


Assuntos
Protocolos Clínicos , Fidelidade a Diretrizes , Maternidades , Hospitais Pediátricos , Corpo Clínico Hospitalar/psicologia , Afeganistão , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa
10.
Neurobiol Dis ; 77: 173-90, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25753471

RESUMO

Down Syndrome (DS), trisomy 21, is characterized by synaptic abnormalities and cognitive deficits throughout the lifespan and with development of Alzheimer's disease (AD) neuropathology and progressive cognitive decline in adults. Synaptic abnormalities are also present in the Ts65Dn mouse model of DS, but which synapses are affected and the mechanisms underlying synaptic dysfunction are unknown. Here we show marked increases in the levels and activation status of TrkB and associated signaling proteins in cortical synapses in Ts65Dn mice. Proteomic analysis at the single synapse level of resolution using array tomography (AT) uncovered increased colocalization of activated TrkB with signaling endosome related proteins, and demonstrated increased TrkB signaling. The extent of increases in TrkB signaling differed in each of the cortical layers examined and with respect to the type of synapse, with the most marked increases seen in inhibitory synapses. These findings are evidence of markedly abnormal TrkB-mediated signaling in synapses. They raise the possibility that dysregulated TrkB signaling contributes to synaptic dysfunction and cognitive deficits in DS.


Assuntos
Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Síndrome de Down/patologia , Receptor trkB/metabolismo , Transdução de Sinais/fisiologia , Sinaptossomos/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Modelos Animais de Doenças , Síndrome de Down/genética , Síndrome de Down/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Sinaptossomos/efeitos dos fármacos
11.
East Mediterr Health J ; 19 Suppl 3: S159-65, 2014 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-24995740

RESUMO

Prime cost determinations can increase managerial effectiveness in budget allocation and strategic planning. This study was designed to calculate the prime cost of clinical laboratory services in Tehran Valiasr Hospital using the activity-based costing (ABC) model. The highest costs were for human recourses (44%) and the lowest for energy (5%). The largest proportion of activities (97%) was by specialists, reflecting the importance of human recourses in prime costs. The highest prime cost was for urinalysis (11% of tests) and the lowest for sodium determination (21% of tests), which demonstrates that prime cost decreases as service frequency increases. The average estimated prime cost was 63% higher than the fees established by the Ministry of Health and Medical Education. The results show that the Tehran Valiasr Hospital laboratory faces a budgetary deficit. The prime cost of services can be reduced by improving human recourse management and standardization of resource consumption.

12.
East Mediterr Health J ; 19 Suppl 3: S25-31, 2014 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-24995756

RESUMO

This parallel, randomized, open-ended clinical trial tested the impact of nicotine replacement pharmacotherapy during the course of methadone treatment among opiate abusers. A total of 424 men entered the study at 4 drug treatment centres in Tehran, Islamic Republic of Iran. The intervention group received a 6-week regimen of nicotine replacement pharmacotherapy at no charge. After 6 months, 211 persons (99.5%) in the control group continued to smoke and 1 person (0.5%) had quit. In the intervention group, 117 (55.1%) persons smoked, 15 (7.1%) persons had quit and 80 (37.7%) had reduced by more than 50% the number of cigarettes they smoked at the start of the study (P < 0.0001). The findings suggest that the use of nicotine replacement pharmacology in tandem with methadone maintenance treatment can lead to dramatically improved efficacy for treatment of dual addictions.

13.
East Mediterr Health J ; 20(3): 151-61, 2014 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-24950072

RESUMO

Despite the strengths in the Iranian medical and health sciences educational system, areas in need of improvement have been noted. The purpose of this study was to understand the views of faculty members at Shiraz University of Medical Sciences about current and future needs for medical and health sciences education, with the goal of improving the quality of the educational system. The data were collected using a Delphi consensus method. Analysis of the findings identified the following key themes among the factors likely to contribute to medical and health sciences education and training: adding and/or increasing student numbers in higher degrees in preference to associate degrees; providing more interactive, student-centred teaching methods; improving the educational content with more practical and research-based courses tailored to society's needs; and an emphasis on outcome-based student evaluation techniques. These changes aim to respond to health trends in society and enhance the close relationship between medical education and the needs of the Iranian society.


Assuntos
Atitude do Pessoal de Saúde , Educação Médica/normas , Docentes de Medicina , Ocupações em Saúde/educação , Currículo , Técnica Delphi , Educação Médica/tendências , Humanos , Irã (Geográfico) , Avaliação das Necessidades , Melhoria de Qualidade , Inquéritos e Questionários
14.
Iran Red Crescent Med J ; 14(5): 265-70, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22829984

RESUMO

BACKGROUND: Physicians in ancient Persia played an important role in the development of medicine in the medieval era. One of the most influential figures of this era was Abu Ali Sina or Ibn Sina, known as Avicenna in the western world. The author of more than 200 books on medicine and philosophy, Avicenna followed and further expanded on the tradition of western philosophy and medicine introduced by Aristotle, Hippocrates and Galen. Few researchers have looked into the different medical issues in his best known work, the Canon of Medicine, particularly with regard to ophthalmology. In this analysis, Avicenna's views on and contributions to the diagnosis and treatment of cataracts in his Canon were elucidated. METHODS: We first reviewed an electronic copy of the Canon and then reviewed other important sources in traditional medicine including the Kamel-al-Sanaeh, Al-Havi (Continents) and Zakhireh-kharazmshahi, available in the Avicenna Special Traditional Medicine Library of Shiraz University of Medical Sciences. We also searched Medline, Embase, Scopus, Iranmedex and Science Iranian Database (SID) with these keywords: "traditional medicine," "Avicenna," "cataract", "Canon", "history", "ophthalmology" and "eye disorders". RESULTS: According to the Canon, nozul-al-maa or cataract is an obstructive disease in which external moisture accumulates between the aqueous humor and the corneal membrane and prevents images from entering the eye. Avicenna classified cataracts on the basis of size, density and color. According to size, he identified two types of cataracts including complete and partial obstruction. According to the Canon, surgical intervention was necessary only for certain indications. Avicenna believed that opacity in the initial stages of cataract could be diminished by medicines and foods, and described several medicines for cataracts. He believed that surgery should be postponed until the liquid accumulation stopped, and the cataract reached its mature state. After surgery, according to Avicenna, the patient should avoid headache-inducing situations because headaches could lead to edema of the layers of the eye. He further emphasized that the patient's psychological status played an important role in the success of surgery. CONCLUSION: An important aspect of Avicenna's contribution to the medical management of cataracts was that he believed they could be cured by medication and nutrition in their early stages without the need for surgery. He also considered the patient's mental status as an important factor contributing to the postoperative prognosis. Our review of Avicenna's writings on eye disorders in the Canon of Medicine suggests that he had a rigorous approach to the diagnosis and management of patients suffering from eye disorders.

15.
Diabetes Obes Metab ; 14(11): 1010-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22687049

RESUMO

AIMS: Induction of inducible nitric oxide synthase (iNOS) in pancreatic islets leads to exaggerated nitric oxide (NO) production associated with dysfunctional ß-cells. We examined insulin secretion, iNOS expression and its relationship to the cAMP system in islets from human type 2 diabetes. METHODS: Insulin, glucagon and cAMP were analysed by RIA; iNOS or phosphodiesterase (PDE) expression by quantitative PCR (qPCR), Western blot and confocal microscopy; cell viability by MTS. RESULTS: Diabetic islets displayed impaired insulin and glucagon responses to glucose, disturbed cAMP generation and high inducible nitric oxide synthase (iNOS) mRNA and protein expression. Confocal microscopy showed iNOS protein expression in diabetic islets being confined to insulin, glucagon and somatostatin cells. Culture of diabetic islets at 5.5 mmol/l glucose with dibutyryl-cAMP (Bt(2) -cAMP) for 24 h was accompanied by marked suppression of iNOS mRNA, reduced nitrite production and increased insulin secretion. Diabetic islets displayed marked increase in PDE3A and PDE3B mRNA expression. Short-time incubation of diabetic islets showed, among the PDE inhibitors tested, cilostazol being most favourable to increase insulin secretion. Diabetic islets were most susceptible to long-term (72 h) culture at high glucose (20 mmol/l) reacting with increased apoptosis. Bt(2) -cAMP and the PDE inhibitors cilostazol, milrinone and IBMX efficiently increased cell viability at high glucose during culture. Defective glucose-stimulated insulin release upon induction of iNOS was restored by iNOS inhibitor aminoguanidine. CONCLUSION: Our results suggest that in islets from type 2 diabetes, stimulatory effects in certain cAMP-compartments induced by PDE inhibitors might play a central role in the suppression of iNOS, resulting in increased ß-cell viability and improved secretory response to glucose.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Glucagon/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Animais , Western Blotting , Diabetes Mellitus Tipo 2/imunologia , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos , Microscopia Confocal , Óxido Nítrico/metabolismo , Ratos
16.
Prog Brain Res ; 197: 199-221, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22541294

RESUMO

This review describes recent discoveries in neurobiology of Down syndrome (DS) achieved with use of mouse genetic models and provides an overview of experimental approaches aimed at development of pharmacological restoration of cognitive function in people with this developmental disorder. Changes in structure and function of synaptic connections within the hippocampal formation of DS model mice, as well as alterations in innervations of the hippocampus by noradrenergic and cholinergic neuromodulatory systems, provided important clues for potential pharmacological treatments of cognitive disabilities in DS. Possible molecular and cellular mechanisms underlying this genetic disorder have been addressed. We discuss novel mechanisms engaging misprocessing of amyloid precursor protein (App) and other proteins, through their affect on axonal transport and endosomal dysfunction, to "Alzheimer-type" neurodegenerative processes that affect cognition later in life. In conclusion, a number of therapeutic strategies have been defined that may restore cognitive function in mouse models of DS. In the juvenile and young animals, these strategists focus on restoration of synaptic plasticity, rate of adult neurogenesis, and functions of the neuromodulatory subcortical systems. Later in life, the major focus is on recuperation of misprocessed App and related proteins. It is hoped that the identification of an increasing number of potential targets for pharmacotherapy of cognitive deficits in DS will add to the momentum for creating and completing clinical trials.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Síndrome de Down , Pesquisa Translacional Biomédica , Fatores Etários , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Transtornos Cognitivos/genética , Modelos Animais de Doenças , Síndrome de Down/complicações , Síndrome de Down/genética , Síndrome de Down/terapia , Humanos , Camundongos , Camundongos Transgênicos , Neurogênese , Plasticidade Neuronal/fisiologia , Neurônios/patologia , Neurônios/ultraestrutura
17.
Diabetologia ; 55(7): 1985-94, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22538358

RESUMO

AIMS/HYPOTHESIS: γ-Aminobutyric acid (GABA) is a signalling molecule in the interstitial space in pancreatic islets. We examined the expression and function of the GABA signalling system components in human pancreatic islets from normoglycaemic and type 2 diabetic individuals. METHODS: Expression of GABA signalling system components was studied by microarray, quantitative PCR analysis, immunohistochemistry and patch-clamp experiments on cells in intact islets. Hormone release was measured from intact islets. RESULTS: The GABA signalling system was compromised in islets from type 2 diabetic individuals, where the expression of the genes encoding the α1, α2, ß2 and ß3 GABA(A) channel subunits was downregulated. GABA originating within the islets evoked tonic currents in the cells. The currents were enhanced by pentobarbital and inhibited by the GABA(A) receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABA(A) channels (GABA(A) receptors) decreased both insulin and glucagon secretion. The GABA(B) receptor antagonist, CPG55845, increased insulin release in islets (16.7 mmol/l glucose) from normoglycaemic and type 2 diabetic individuals. CONCLUSIONS/INTERPRETATION: Interstitial GABA activates GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Antagonistas GABAérgicos/farmacologia , Células Secretoras de Insulina/metabolismo , Piridazinas/farmacologia , Receptores de GABA-B/metabolismo , Ácido gama-Aminobutírico/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Homeostase , Humanos , Imuno-Histoquímica , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Receptores de GABA-B/genética , Transdução de Sinais/efeitos dos fármacos , Ácido gama-Aminobutírico/efeitos dos fármacos , Ácido gama-Aminobutírico/genética
18.
Adv Biomed Res ; 1: 87, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23946935

RESUMO

BACKGROUND: To setup a non-invasive genetic screening method for colorectal cancer, we evaluated the promoter methylation status of secreted frizzled-related protein1 (sfrp1) in stool samples of colorectal cancer with respect to a series of healthy individuals, using methylation-specific polymerase chain reaction. MATERIALS AND METHODS: In stool samples from 25 patients with colorectal cancer and 25 healthy control subjects, isolated DNA was treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the SFRP1 gene. RESULT: Methylation of the SFRP1 promoter was present in the stool DNA of patients with colorectal cancer. A sensitivity of 52% and specificity of 92% were achieved in the detection of colorectal neoplasia. The difference in methylation status of the SFRP1 promoter between the patients with colorectal neoplasia and the control group was statistically highly significant (P = 0.006). CONCLUSIONS: The results indicate that this DNA stool test of methylation of the SFRP1 promoter is a sensitive and specific method. It is assumed that the test is potentially useful for the early detection of colorectal cancer.

19.
East Mediterr Health J ; 18(11): 1143-50, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23301377

RESUMO

To improve the quality of research, it is necessary to understand the obstacles to undertaking research. This study aimed to identify: I) internal obstacles to research as considered by faculty members at Shiraz University of Medical Sciences; ii) differences between their viewpoints by gender and professional variables; and iii) the effect of these obstacles on research activity. Six types of obstacle were considered: financial, facility-related, occupational, managerial-organizational, scientific and personal. The study sample consisted of 240 participants selected from all 550 faculty members of the University. Data were collected by self-administered questionnaire; the response rate was 91%. All 6 types of obstacle were considered to affect research activities by most of the respondents, with 90% identifying financial obstacles. There were significant differences by gender, scientific rank, field of study, and holding executive responsibilities but not for durations of work experience. Despite these numerous obstacles to conducting research, respondents did not think their research output was affected.


Assuntos
Pesquisa Biomédica/organização & administração , Docentes , Faculdades de Medicina/organização & administração , Atitude do Pessoal de Saúde , Pesquisa Biomédica/economia , Feminino , Humanos , Irã (Geográfico) , Masculino , Projetos de Pesquisa , Apoio à Pesquisa como Assunto , Fatores Sexuais , Carga de Trabalho
20.
Arch Orthop Trauma Surg ; 132(2): 171-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22006572

RESUMO

PURPOSE: Long-term success of contemporary total knee replacements relies to a large extent on proper implant alignment. This study was undertaken to test whether specimen-matched cutting blocks based on computed axial tomography (CT) scans could provide accurate rotational alignment of the femoral component. METHODS: CT scans of five fresh frozen full leg cadaver specimens, equipped with infrared reflective markers, were used to produce a specimen-matched femoral cutting block. Using those blocks, the bone cuts were made to implant a bi-compartmental femoral component. Rotational alignment of the components in the horizontal plane was determined using an optical measurement system and compared with all relevant rotational reference axes identified on the CT scans. RESULTS: Average rotational alignment for the bi-compartmental component in the horizontal plane was 1.9° (range 0°-6.3°; standard deviation 2.6°). One specimen that showed the highest deviation from the planned alignment also featured a completely degraded medial articular surface. CONCLUSIONS: The CT-based specimen-matched cutting blocks achieved good rotational alignment accuracy except for one specimen with badly damaged cartilage. In such cases, imaging techniques that visualize the cartilage layer might be more suitable to design cutting blocks, as they will provide a better fit and increased surface support.


Assuntos
Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Tomografia Computadorizada por Raios X , Idoso , Cadáver , Humanos
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