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Background: The aim of this study was to assess the COVID-19-related knowledge, attitudes, and practice among dental students (DS) and internship students at Ajman University (AU). Methods: A cross-sectional, web-based study was conducted among Ajman dental college students registered in the academic year 2019/2020, about COVID-19 during the first week of April 2020. A questionnaire was developed and distributed to all DS to examine their knowledge and attitudes toward the COVID-19 pandemic. Chi-square (χ2) test was used to investigate the level of association among categorical variables at the significance level of p < 0.05. Results: Out of 769 students in the dental college, majority (75%) had adequate knowledge of COVID-19, but only 40.6% of the participants projected a positive attitude. A positive behavior was reported by an overwhelming 94.5% of the participants. Participants above 25 years of age had significantly higher (p < 0.001) adequate knowledge (88.2%), positive attitude (56.9%), and positive behavior (100%) compared to those below 25 years of age. Study participants reported social media (71.1%), government websites (63.7%), and family and friends (41.0%) as top three sources of information regarding COVID-19 related information. Conclusion: The results of this study show that AU dental and internship students have adequate knowledge and positive attitude of the COVID-19 pandemic but the majority are not eager to adopt effective strategies to avoid the spread of COVID-19 (practice). Further education should be offered to encourage efficient infection management practices to protect students, faculty, and other university staff.
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BACKGROUND: Post-marketing surveillance of drugs is a cornerstone of pharmacovigilance. This study was conducted to characterize patterns of adverse drug reactions (ADRs) reported in Jordan. RESEARCH DESIGN AND METHODS: ADR reports submitted to the pharmacovigilance database of the Jordan Food and Drug Administration during 2015-2021 were retrospectively analyzed. The most commonly reported drugs, drug classes, ADRs, and ADRs consequences were explored. Logistic regression identified possible predictors of reporting serious ADRs. RESULTS: A total of 2744 ADR reports were included, among which 28.4% were classified as serious. An annual increase in ADR reporting was observed. The most commonly implicated drug classes were antineoplastic and immunomodulating agents (24.0%), anti-infectives for systemic use (14.2%), and alimentary tract and metabolism (12.1%). Covid-19 vaccination was the most reported drug (22.8%). Fatigue (6.3%), injection site pain (6.1%), and headache (6.0%) were the top three common ADRs. Among ADRs with outcome information, 4.7% were fatal. Patient's age and intravenous medication use largely predicted reporting serious ADRs. CONCLUSIONS: This study provides contemporary insights into the post-marketing surveillance of drugs in Jordan. The findings are foundational for future studies exploring drug-ADRs causality relationships. Efforts that promote pharmacovigilance concepts should be sustained and enhanced at the national level.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Humanos , Estudos Retrospectivos , Jordânia/epidemiologia , Vacinas contra COVID-19 , Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
Background: Achieving widespread coronavirus disease 2019 (COVID-19) vaccination is crucial in controlling the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This cross-sectional study aimed to identify factors associated with the willingness of dental medicine students to receive the COVID-19 vaccine. Objectives: The study sought to assess the knowledge, attitudes, and behaviors of undergraduate dental students toward COVID-19 vaccines and to identify determinants, motivators, and barriers to vaccine uptake and booster receipt. Methods: A web-based survey was distributed to all 882 undergraduate dental surgery students in January 2022, and 70.7% of the students responded. The survey used χ2 tests and logistic regression analysis to examine the association among the variables. The significance level was set at α = 0.05. Results: Most participants (72.4%) reported having adequate knowledge of COVID-19. The vaccine acceptance rate was higher among male and older trainees, with no significant difference compared to women and younger trainees with no significant difference (p = 0.849). Acceptance of the vaccine varied according to study level (5-year program), ranging from 44.8% to 73.0%, in the following order 4th > 1st > 3rd > 5th > 2nd year. Social media (76.8%), government websites (66.5%), and family and friends (57.2%) were the main sources of COVID-19-related information. Among hesitant and unwilling participants, the main concerns were side effects (34.0%) and lack of understanding about the vaccine's mechanism (67.3%). Conclusions: Ajman dental students had moderate knowledge of COVID-19 and obtained information mainly from social media, government websites, and family and friends. Age, sex, and study year influenced vaccine acceptance. The main reasons for refusal were lack of knowledge, fear of side effects, and complications. Education campaigns are needed to increase vaccine acceptance among dental students.
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Objective: Systemic capillary leak syndrome (SCLS) is a severe condition characterized by the coexistence of hypovolaemic shock, haemococentration, and hypoalbuminaemia, without albuminuria, that may progress to multiorgan failure and an unfavourable outcome. Its development is often triggered by viral infections, such as influenza A virus, but it is unclear whether it is also triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We aimed to investigated the association between SARS-CoV-2 and SCLS.Method: We present the case of a 55-year-old-woman affected by SARS-CoV-2 infection who developed SCLS. Moreover, we performed a systematic review of the literature to identify any common features with other cases and to describe clinical characteristics and outcomes.Results: We found three other cases of SCLS occurring during SARS-CoV-2 infection in 2020. Taking all cases together, the mean age was 50 years (range 38-63), with a 1:1 gender ratio. Respiratory manifestations were the most common symptom, and all patients required admission to the intensive care unit. The mortality rate was 50%.Conclusions: SARS-CoV-2 infection may trigger SCLS disease, either by an overproduction of proinflammatory cytokines or by direct viral infection of the endothelium. Since SCLS may have a poor prognosis, in every SARS-CoV-2-infected patient presenting the suggestive triad of hypovolaemic shock, haemoconcentration, and hypoproteinaemia, an SCLS diagnosis should be considered and early treatment initiated.
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COVID-19 , Síndrome de Vazamento Capilar , Adulto , COVID-19/complicações , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Oral squamous cell carcinoma (OSCC) is the most commom cancer in the world. If remain untreated for several years, it may be fatal. Hence, it is important to prevent and treat OSCC at an early stage. In this study the effect of aqueous and dry leaves extract of Ocimum sanctum was observed on Ca9-22 cell line, which is an OSCC cell line. For this, Ca9-22 cell line was cultured and maintained. After 24 h, the cells were treated with aqueous and dry leaves extract of Ocimum sanctum plant. Viability of the cancerous cells were studied by 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and neutral red uptake (NRU) assay. Minimum inhibitory concentrations (MIC), lethal concentration25 (LC25), lethal concentration50 (LC50) and highest permissive concentration (HPC) was calculated by probit computational method. Experimentally, the MIC value was 5 mg/L, whereas the HPC was 30 mg/L of the plant extract in aqueous state. For the dry extract the MIC was 5 mg/L whereas the HPC was 35 mg/L for both MTT and NRU assays. For MTT assay LC values: 7.41 (LC25), 14.79 (LC50) and 26.91 mg/L (LC75) for aqueous extract and 12.58 (LC25), 20.89 (LC50), 29.51 mg/L (LC75) for dry extract. For NRU assay LC values were 10.23 (LC25), 14.79 (LC50) and 20.89 mg/L (LC75) aqueous extract, and 16.59 (LC25), 23.44 (LC50), 30.19 mg/L (LC75) dry extract of the plant. From the above study it was concluded that, Ocimum sanctum have anti-cancerous activity. It can further be used for therapeutic purposes.
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Multiple Myeloma (MM) is the third most common and deadly hematological malignancy, which is characterized by a progressive monoclonal proliferation within the bone marrow. MM is cytogenetically heterogeneous with numerous genetic and epigenetic alterations, which lead to a wide spectrum of signaling pathways and cell cycle checkpoint aberrations. MM symptoms can be attributed to CRAB features (hyperCalcemia, Renal failure, Anemia, and Bone lesion), which profoundly affect both the Health-Related Quality of Life (HRQoL) and the life expectancy of patients. Despite all enhancement and improvement in therapeutic strategies, MM is almost incurable, and patients suffering from this disease eventually relapse. Curcumin is an active and non-toxic phenolic compound, isolated from the rhizome of Curcuma longa L. It has been widely studied and has a confirmed broad range of therapeutic properties, especially anti-cancer activity, and others, including anti-proliferation, anti-angiogenesis, antioxidant and anti-mutation activities. Curcumin induces apoptosis in cancerous cells and prevents Multidrug Resistance (MDR). Growing evidence concerning the therapeutic properties of curcumin caused a pharmacological impact on MM. It is confirmed that curcumin interferes with various signaling pathways and cell cycle checkpoints, and with oncogenes. In this paper, we summarized the anti- MM effects of curcumin.
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Antineoplásicos Fitogênicos/farmacologia , Curcuma/química , Curcumina/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologiaRESUMO
There is urgent need to address illness problems caused by Salmonella enteric serotype Typhibacteria. The bacteria are deposited in water or food by human carrier and are then spread to other people in the area. In this research, a blood specimens were collected from typhoid fever patients, and serum levels of IFN-γ and IL-6 during the chronic and acute phase in typhoid patients group was determined according protocol kit and calculation, results were higher levels in chronic phase (137.187 ± 0.703.427 ± 206.545pg/ml respectively) and in acute phase were 128.787 ± 2.522, 137.733 ± 23.424 pg/ml, respectively with highly significant (P ≤ 0.01) than those in healthy control group. Salmonella infects hosts as diversified as human, animal, and plant
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Humanos , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Salmonella , Sorologia , Febre Tifoide/terapia , Coleta de Amostras SanguíneasRESUMO
Organoclays have been applied as efficient adsorbents for pharmaceutical pollutants from aqueous solution. In this work, dodecylpyridinium chloride (C12pyCl) and hexadecylpyridinium chloride (C16pyCl) cationic surfactants were used for the preparation of organobentonites destined for diclofenac sodium (DFNa) adsorption, an anionic drug widely detected in wastewater. The organofunctionalization of the clay samples was performed under microwave irradiation at 50⯰C for 5â¯min with surfactant amounts of 100% and 200% in relation to the cation exchange capacity (CEC) of the pristine bentonite. The amount of incorporated ammonium salts based on CHN elemental analysis was higher for all samples prepared with 200% of the CEC. The basal spacings of the organoclays ranged from 1.54 to 2.13â¯nm, indicating the entrance of organic cations into the interlayer spacing of the clay samples, and the spacing depended on the size of the alkyl organic chain. The hydrophobic character of the organobentonites was verified by thermogravimetry and infrared spectroscopy (FTIR). The adsorption isotherms showed that the drug capacity adsorption was influenced by the amount of surfactant incorporated into the bentonite, the packing density and the arrangement of the surfactants in the interlayer spacing. Zeta potential measurements of the organobentonites and FTIR analysis after drug adsorption suggested that electrostatic and nonelectrostatic interactions contributed to the mechanism of adsorption.
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Bentonita/química , Diclofenaco/química , Adsorção , Anti-Inflamatórios não Esteroides/química , Cátions/química , Interações Hidrofóbicas e Hidrofílicas , Eletricidade Estática , Tensoativos/química , Água/química , Difração de Raios XRESUMO
Cyanobacteria have long been thought to induce the formation of Ca-carbonates as secondary by-products of their metabolic activity, by shifting the chemical composition of their extracellular environment to conditions favoring mineral precipitation. Some cyanobacterial species forming Ca-carbonates intracellularly were recently discovered. However, the environmental conditions under which this intracellular biomineralization process can occur and the impact of cyanobacterial species forming Ca-carbonates intracellularly on extracellular carbonatogenesis are not known. Here, we show that these cyanobacteria can form Ca-carbonates intracellularly while growing in extracellular solutions undersaturated with respect to all Ca-carbonate phases, that is, conditions thermodynamically unfavorable to mineral precipitation. This shows that intracellular Ca-carbonate biomineralization is an active process; that is, it costs energy provided by the cells. The cost of energy may be due to the active accumulation of Ca intracellularly. Moreover, unlike cyanobacterial strains that have been usually considered before by studies on Ca-carbonate biomineralization, cyanobacteria forming intracellular carbonates may slow down or hamper extracellular carbonatogenesis, by decreasing the saturation index of their extracellular solution following the buffering of the concentration of extracellular calcium to low levels.
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Carbonato de Cálcio/metabolismo , Cyanothece/metabolismo , Cálcio/metabolismo , Técnicas de Cultura , Cyanothece/crescimento & desenvolvimentoRESUMO
SCIENTIFIC BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning. This line of study may generate new knowledge and understanding of motor symptoms associated with ASD and aims to deliver fresh perspectives for early diagnosis and therapeutic strategies against ASD. AIMS OF THE REVIEW: Despite the relative paucity of research in this area (compared to the social, linguistic, and behavioural disturbances in ASD), there is evidence that the frontostriatal motor system and/or the cerebellar motor systems may be the site of dysfunction in ASD. Indeed, the cerebellum seems to be essential in the development of basic social capabilities, communication, repetitive/restrictive behaviors, and motor and cognitive behaviors that are all impaired in ASD. Cerebellar neuropathology including cerebellar hypoplasia and reduced cerebellar Purkinje cell numbers are the most consistent neuropathologies linked to ASD. The functional state of the cerebellum and its impact on brain function in ASD is the focus of this review. This review starts by recapitulating historical findings pointing towards an implication of the cerebellum, and to a lesser extent the basal ganglia structures, in TSA. We then detail the structure/function of the cerebellum at the regional and cellular levels before describing human and animal findings indicating a role of the cerebellum and basal ganglia in ASD. HUMAN AND ANIMAL FINDINGS: Several studies have attempted to identify the nature of the motor system dysfunction in ASD, and it became apparent that the motor fronto-striatal and cerebellar systems are major sites of dysfunction in this psychiatric illness. Anomalies in these structures have been revealed both at the anatomical and functional levels in human patients as well as in animal models. These models are obtained by manipulation of genes that are often implicated in glutamate transmission, by lesions of brain structures among which the cerebellum, by pharmacological treatment with drugs such as the Valproate or by maternal infections with bacterial membrane extracts of double stranded RNA mimicking a viral infection. CONCLUSION: The "cognitive approach" has dominated ASD research for three decades and led to the design of interventional strategies, which have yielded satisfactory results. Nevertheless, new approaches and alternative hypotheses on the aetiology and diagnosis of ASD are needed. Research focused on motor rather than psychiatric symptoms may have a greater potential to elucidate the neurobiological basis of ASD.
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Transtorno do Espectro Autista/fisiopatologia , Cerebelo/fisiopatologia , Transtornos Motores/psicologia , Transtornos dos Movimentos/psicologia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Cognição/fisiologia , Humanos , Desenvolvimento da Linguagem , Transtornos Motores/fisiopatologia , Transtornos dos Movimentos/fisiopatologia , Postura/fisiologia , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/etiologia , Distúrbios da Fala/fisiopatologiaRESUMO
Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself.
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Artrite Reumatoide/diagnóstico por imagem , Densidade Óssea , Glucocorticoides/efeitos adversos , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Pré-Menopausa , Absorciometria de Fóton/métodos , Adulto , Artrite Reumatoide/tratamento farmacológico , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Colo do Fêmur/diagnóstico por imagem , Glucocorticoides/administração & dosagem , Humanos , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Pacientes Ambulatoriais , Fatores de Risco , Coluna Vertebral/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
Despite the fact that G protein-coupled receptors (GPCRs) mediate numerous physiological processes and represent targets for therapeutics for a vast array of diseases, their role in tumor biology is under appreciated. Protease-activated receptors (PARs) form a family which belongs to GPCR class A. PAR1&2 emerge with a central role in epithelial malignancies. Although the part of PAR1&2 in cancer is on the rise, their underlying signaling events are poorly understood. We review hereby past, present, and future cancer-associated PAR biology. Mainly, their role in physiological (placenta-cytotophobalst) and patho-physiological invasion processes. The identification and characterization of signal pleckstrin homology (PH)-domain-binding motifs established critical sites for breast cancer growth in PAR1&2. Among the proteins found to harbor important PH-domains and are involved in PAR biology are Akt/PKB as also Etk/Bmx and Vav3. A point mutation in PAR2, H349A, but not R352A, abrogated PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumor growth in vivo as also placental extravillous trophoblast (EVT) invasion in vitro is markedly reduced. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind PH-domain, inhibits mammary tumors and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.
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Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Receptores Ativados por Proteinase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Terapia de Alvo MolecularRESUMO
Organically modified vermiculites were synthesized by previous silylation of three leached vermiculites, V0.3Cl, V0.5Cl and V0.8Cl, under anhydrous conditions following reaction with imidazole (Im), which acted as chelating agent for copper retention. Elemental analysis, X-ray diffraction, infrared spectroscopy, scanning electronic microscopy, transmission electron microscopy, (29)Si and (13)C NMR and nitrogen adsorption/desorption measurements were used to characterize pristine, leached and organofunctionalized solids. X-ray photoelectron spectroscopy (XPS) was used to evaluate the surface after copper sorption. Parameters such as contact time, pH and initial cation concentration for the adsorption of Cu(II) ions were investigated. The adsorption equilibrium data were fitted using the Langmuir isotherm model and the monolayer adsorption capacities were 2.38, 2.52 and 2.69mmolg(-1) for V0.5Cl-Im, V0.3Cl-Im and V0.8Cl-Im, respectively, at pH 6.0 and 298K for a time reaction of 80min. The sorption rates were described by pseudo-second-order kinetics. The chloropropyl imidazole vermiculites are promising adsorbents for the rapid removal of Cu(II) ions from aqueous solution.
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Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.
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Neoplasias da Mama/genética , Placenta/metabolismo , Receptor PAR-1/genética , Receptor PAR-2/genética , Trofoblastos/metabolismo , Animais , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Técnicas de Inativação de Genes , Células HCT116 , Células HEK293 , Humanos , Imuno-Histoquímica , Imunoprecipitação , Técnicas In Vitro , Células MCF-7 , Glândulas Mamárias Animais/patologia , Mutação , Invasividade Neoplásica , Transplante de Neoplasias , Placenta/fisiologia , Gravidez , Estrutura Terciária de Proteína , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Trofoblastos/fisiologiaRESUMO
Parkinson's disease (PD) is the most common movement disorder in Europe, affecting more than two million people between 50 and 70 years of age. The current therapeutic approaches are of symptomatic nature and fail to halt the progressive neurodegenerative course of the disease. The development of innovative and complementary approaches to promote cellular repair may pave the way for disease-modifying therapies which may lead to less suffering for the patients and their families and finally to more cost-effective therapies. To date, cell replacement trials in PD aiming at replacing lost dopamine neurons were mainly focused on placing the transplanted cells within the target site, the striatum, and not within the lesioned site, the substantia nigra (SN). This was based on the misconception that the adult brain constitutes a non-permissive barrier not allowing the outgrowth of long distance axons originating from transplanted embryonic neurons. A growing body of evidence is challenging this concept and proposing instead to place the graft within its ontogenic site. This has been performed in several lesional animal models for various traumatic or neurodegenerative pathologies of the brain. For instance, transplanted neurons within the lesioned motor cortex were shown to be able to send distant and appropriate projections to target areas including the spinal cord. Similarly, in an animal model of PD, mesencephalic embryonic cells transplanted within the lesioned SN send massive projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens. This has lead to the proposal that homotopic transplantation may be an alternative in cell-based therapies as transplanted neurons can integrate within the host brain, send projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior. We will discuss also the potential of replacing embryonic neuronal cells by stem cell derived neurons as the use of embryonic cells is not without an ethical and logistical burden; in this line many have thrived to derive neurons from embryonic stem cells (ESC) in order to use them for cell transplantation. These studies are already yielding important information for future approaches in the field of cell therapies in PD but also in other neurodegenerative disorders where cell transplantation therapy may be considered. While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted PD patients, these new sets of findings are raising new hopes and opening new avenues in this rejuvenated field.
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Encéfalo/patologia , Transplante de Células/métodos , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Adulto , Animais , Comportamento/fisiologia , Corpo Estriado/patologia , Corpo Estriado/transplante , Humanos , Degeneração Neural/patologia , Degeneração Neural/terapia , Rede Nervosa/patologia , Substância Negra/patologia , Substância Negra/transplanteRESUMO
In addition to the known preventive effects of environmental enrichment (EE) on drug addiction, we have recently shown that EE can also have "curative" effects and eliminate addiction-related behaviors in mice and rats. In the present study, using Fos immunohistochemistry, we investigated brain regions involved in the elimination of cocaine conditioned place preference (CPP) produced by a 30-day exposure to EE. A first group of mice was conditioned to cocaine in the CPP apparatus, a second group that served as control received cocaine in a cage different from the CPP apparatus and a third control group received only saline injections. At the end of conditioning, we kept mice abstinent in the animal facility, housing them in standard environments (SE) or EE for 30 days and then we tested them for expression of CPP. SE, but not EE mice, conditioned to cocaine showed long-lasting preferences for the cocaine-paired compartment. Expression of CPP was paralleled by significant increases in the expression of Fos in the anterior cingulate cortex, the lateral caudate putamen, the shell of the nucleus accumbens, the dentate gyrus of the hippocampus, the basolateral and central nuclei of amygdala, the bed nucleus of the stria terminalis, and the ventral tegmental area. In contrast, EE mice showed levels of expression of FOS similar to control groups. These results demonstrate that EE can eliminate context-induced cocaine seeking and that this effect appears associated with a general reduction in the activation of several brain regions implicated in relapse.
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Encéfalo/efeitos dos fármacos , Cocaína/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Meio Ambiente , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Reforço PsicológicoRESUMO
Identifying guidance cues that direct axon growth to their final connections during development is of crucial interest if we aim to repair circuits damaged in adulthood following neurodegenerative disorders or common traumatic injuries. In this work, we set out to determine the ephrinA5 guidance molecule involvement in the establishment of the mouse mesostriatal pathway during development. We showed, in vitro and in vivo, that a proportion of mesencephalic dopaminergic cells express the ephrinA5 receptor, EphA5. Moreover, we observed, using stripe assays, that ephrinA5 purified protein has a repulsive effect on most of the mesencephalic dopaminergic projections. In vivo, we detected rostro-caudal and ventro-dorsal ephrinA5 protein expression gradients in the vicinity of the dopaminergic axons in the ventral telencephalon and in the striatum, during the embryonic and early postnatal development. In addition, other EphA5 ligands were also detected in the mesostriatal pathway. Together, these expression patterns suggest that, ephrinAs and more specifically ephrinA5, may be actors in the guidance of dopaminergic projections. Further studies will focus on identifying the molecular specificity of these guidance cues, taking into account the mesencephalic dopaminergic heterogeneous neuronal population. This may help increase the integration of neuronal transplants in the mature lesioned brain or provide tools to re-establish mesostriatal circuits in vivo.
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Corpo Estriado/citologia , Efrina-A5/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Mesencéfalo/citologia , Neurônios/fisiologia , Animais , Animais Recém-Nascidos , Axônios/efeitos dos fármacos , Axônios/fisiologia , Células Cultivadas , Embrião de Mamíferos , Efrina-A5/deficiência , Efrina-A5/genética , Efrina-A5/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vias Neurais/fisiologia , Neurônios/citologia , RNA Mensageiro/metabolismo , Receptores da Família Eph/genética , Receptores da Família Eph/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
BACKGROUND: Clostridium difficile infection (CDI) is a frequent cause of morbidity and mortality among elderly hospitalized patients. A small but increasing number of patients have developed fulminant CDI, and a significant number of these patients require emergency colectomy. In this review, we discuss the risk factors, pathophysiology, diagnosis, and management of fulminant CDI. DATA SOURCES: A literature search (Medline, Embase, Cochrane Library, Biosis, Science Citation Index, Ovid Journals) was performed from the period between January 1980 and June 2008 using the key words "Clostridium difficile,""pseudomembranous enterocolitis,""colectomy,""acute abdomen,""antibiotic-associated diarrhea," or "fulminant Clostridium difficile colitis." Articles not in English or not related to human subjects were excluded. For this review, we analyzed the articles identified in our original search and those articles cited in the original review articles. No randomized trials were found on the surgical management of fulminant CDI and only retrospective studies with a minimum of five patients were used in the review. With respect to medical treatment, we based our review on guideline articles, systematic reviews, and available randomized trials. CONCLUSION: Both the incidence and severity of CDI are increasing. Fulminant CDI is underappreciated as a life-threatening disease because of a lack of awareness of its severity and its nonspecific clinical syndrome. Early diagnosis and treatment are essential for a good outcome, and early surgical intervention should be used in patients who are unresponsive to medical therapy. The surgical procedure of choice is a total abdominal colectomy with end ileostomy, although the mortality rate remains high.