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1.
J Eur Acad Dermatol Venereol ; 36(5): 705-716, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35015907

RESUMO

BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities. OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research. METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.


Assuntos
Dermatite Atópica , Microbiota , Animais , Bactérias , Citocinas , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Humanos , Interleucina-33 , Interleucina-4 , Camundongos , Oxazolona/efeitos adversos , Pele
2.
Forensic Sci Int ; 329: 111053, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34700246

RESUMO

Cannabis sativa is the most used controlled substance in Europe. With the advent of new and less restrictive European laws on cannabis sale for recreational use (including in Italy), an increase in indoor cannabis crops were observed. This increase was possible due to the availability of cannabis seeds through the internet market. Genetic identification of cannabis can link seizures and if in possession then might aid in an investigation. A 13-locus multiplex STR method was previously developed and validated by Houston et al. A collaborative exercise was organized by the Italian Forensic Geneticists - International Society of Forensic Genetics (Ge.F.I. - ISFG) Working Group with the aim to test the reproducibility, reliability and robustness of this multiplex cannabis STR kit. Twenty-one laboratories from three European countries participated in the collaborative exercise and were asked to perform STR typing of two cannabis samples. Cannabis DNA samples and the multiplex STR kit were provided by the University of Barcelona and Sam Houston State University. Different platforms for PCR amplification, capillary electrophoresis (CE) and genotyping software were selected at the discretion of the participating laboratories. Although the participating laboratories used different PCR equipment, CE platforms and genotyping software, concordant results were obtained from the majority of the samples. The overall genotyping success ratio was 96%. Only minor artifacts were observed. The mean peak height ratio was estimated to be 76.3% and 78.1% for sample 1 and sample 2, respectively. The lowest amount of -1 / + 1 stutter percentage produced, when the height of the parent allele was higher than 8000 RFU, resulted to be less than 10% of the parent allele height. Few common issues were observed such as a minor peak imbalance in some heterozygous loci, some artifact peaks and few instances of allelic drop-out. The results of this collaborative exercise demonstrated the robustness and applicability of the 13-locus system for cannabis DNA profiling for forensic purposes.


Assuntos
Cannabis , Cannabis/genética , DNA , Impressões Digitais de DNA , Humanos , Repetições de Microssatélites , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes
3.
Eur Rev Med Pharmacol Sci ; 25(4): 1774-1787, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33660786

RESUMO

OBJECTIVE: The aim of this review was to explore recent pieces of evidence focused on the use of miRNAs for PMI estimation both in humans and animal experiments, with particular interest on the best miRNAs to use as reference/target markers in different tissues or biological fluids. MiRNAs are innovative biomarkers used in clinical and research field; they appear very attractive, being introduced in forensic research scenarios even for PMI estimation. MATERIALS AND METHODS: Data from PubMed and Scopus were analyzed from January 2013 to August 2020. Based on inclusion/exclusion criteria, high-quality articles have been selected to become the subject of this review. RESULTS: A total of 737 papers were found but, after titles/abstracts screening for inclusion criteria and a full-text careful selection, 33 papers were deeply studied. After the exclusion of 19 papers, 15 articles remained. Eight papers dealt with animals (mice/rats), two both with animals and humans (for method validation previously built), while 5 exclusively with humans. Myocardium (6/15) and brain (6/15) were the most studied tissues, respectively in mice/rats and humans. PMI considered was up to 7.5 days in mouse studies and less than 3 days in human models. CONCLUSIONS: Because of their significant stability in both early and long PMI, miRNAs are the cleverest reference markers to be used. Temperature and environmental conditions influence mostly mRNA, while miRNAs are less susceptible to them. The best miRNA to choose depends on its tissue specificity, i.e., miR-9 and miR-125 in brain or miR-1 and miR-133 in skeletal muscle/heart.


Assuntos
MicroRNAs/genética , Mudanças Depois da Morte , Patologia Legal , Humanos , Reação em Cadeia da Polimerase
4.
Allergy ; 74(8): 1549-1560, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30829405

RESUMO

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only causal treatment for allergy. However, success rates vary depending on the type of allergy and disease background of the patient. Hence, strategies targeting an increased therapeutic efficacy are urgently needed. Here, the effects of blockade of IL-4 and IL-13 signaling on different phases of AIT were addressed. METHODS: The impact of the recombinantly produced IL-4 and IL-13 antagonist IL-4 mutein (IL-4M) on allergic sensitization and AIT outcome in experimental allergic asthma were analyzed in a murine model. The effects of IL-4M administration were assessed prior/during sensitization, immediately after AIT under allergen challenge, and two weeks post-treatment. RESULTS: Intervention with IL-4M prior/during sensitization led to strong induction of IgG1, IgG2a, IgG2b, and IgG3, decrease of specific and total IgE, as well as of IL-5 in serum. Similar effects on the serum immunoglobulin levels were observed immediately after IL4M-supplemented AIT during allergen challenge. Additionally, IL4M markedly suppressed type-2 cytokine secretion of splenocytes beyond the effect of AIT alone. These effects were equaled to those of AIT alone two weeks post-treatment. Intriguingly, here, IL-4M induced a sustained decrease of Th2-biased Tregs (ST2+ FOXP3+ GATA3intermediate ). CONCLUSIONS: IL-4 and IL-13 blockade during experimental AIT demonstrates beneficial effects on immunological key parameters such as immunoglobulin and cytokine secretion immediately after AIT. Although two weeks later these effects were dropped to those of AIT alone, the number of potentially disease-triggering Th2-biased Tregs was further significantly decreased by IL-4M treatment. Hence, IL-4/IL13-targeting therapies prime the immune memory in therapy success-favoring manner.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Asma/terapia , Dessensibilização Imunológica , Subunidade alfa de Receptor de Interleucina-4/antagonistas & inibidores , Alérgenos/administração & dosagem , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Asma/metabolismo , Diferenciação Celular/imunologia , Dessensibilização Imunológica/métodos , Modelos Animais de Doenças , Feminino , Imunização , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-4/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
5.
Mult Scler Relat Disord ; 17: 9-11, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29055482

RESUMO

We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture. This is the first reported case of Marburg type multiple sclerosis treated with alemtuzumab.


Assuntos
Alemtuzumab/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Resultado do Tratamento
6.
Allergy ; 72(12): 1962-1971, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28513859

RESUMO

BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach. METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.


Assuntos
Asma/diagnóstico , Asma/genética , Biomarcadores , MicroRNA Circulante , Transcriptoma , Adulto , Idoso , Animais , Asma/sangue , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Pesquisa Translacional Biomédica , Adulto Jovem
7.
Allergy ; 70(11): 1450-60, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26214762

RESUMO

BACKGROUND: B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization. METHODS: B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days. RESULTS: Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation. CONCLUSIONS: Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.


Assuntos
Alérgenos/imunologia , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Imunoglobulina E/imunologia , Pólen/imunologia , Células Th2/imunologia , Ambrosia/imunologia , Animais , Antígenos de Plantas/imunologia , Linfócitos B/metabolismo , Feminino , Humanos , Imunização , Memória Imunológica , Ativação Linfocitária/imunologia , Camundongos , Ovalbumina/imunologia , Extratos Vegetais/imunologia , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Células Th2/metabolismo
8.
Allergy ; 70(8): 944-54, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25939785

RESUMO

BACKGROUND: Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation. METHODS: Aqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1-11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen-derived adenosine was removed from the extract enzymatically to analyze its role in ragweed-induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed-stimulated bronchial epithelial cells was analyzed. RESULTS: Instillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2-associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present. CONCLUSIONS: Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen-independent pathways.


Assuntos
Adenosina/metabolismo , Antígenos de Plantas/imunologia , Imunização/métodos , Extratos Vegetais/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Administração Intranasal , Animais , Asma/imunologia , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Humanos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Medição de Risco , Sensibilidade e Especificidade , Células Th2/imunologia , Células Th2/metabolismo
9.
Forensic Sci Int Genet ; 10: 64-72, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24603342

RESUMO

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories.


Assuntos
Repetições de Microssatélites , Humanos , Inquéritos e Questionários
10.
Forensic Sci Int Genet ; 7(1): e15-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22917816

RESUMO

The 2011 collaborative exercise of the ISFG Italian Working Group GeFI was aimed at validating the five ENFSI/EDNAP miniSTR loci D1S1656, D2S441, D10S1248, D12S391 and D22S1045. The protocol required to type at least 50 multilocus profiles from locally resident individuals and two blind bloodstains in duplicate (i.e., using at least two different commercial kits), and to send the electropherograms to the Organizing Committee. Nineteen laboratories distributed across Italy participated, collecting a total of 960 samples. Full concordance was found for the five new miniSTRs as observed from the comparison of 13,150 alleles. The inspection of the electropherograms allowed the identification of a very limited number of mistypings in the miniSTR genotypes thus contributing to the establishment of an high quality Italian database of frequencies.


Assuntos
Mapeamento Cromossômico , Genética Populacional , Genética Forense , Humanos , Itália , Laboratórios , Repetições de Microssatélites
11.
Clin Neurophysiol ; 123(1): 142-53, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21741301

RESUMO

OBJECTIVE: To investigate blood oxygenation level-dependent (BOLD) activation during somatosensory electrical stimulation of the median nerve in acute stroke patients and to determine its correlation with ischemic damage and clinical recovery over time. METHODS: Fourteen acute stroke patients underwent functional magnetic resonance imaging (fMRI) during contralesional median-nerve electrical stimulation 12-48 h after stroke. Findings were then validated by diffusion tensor imaging (DTI) and motor evoked potential by transcranial magnetic stimulation (TMS). RESULTS: Poor clinical recovery at three months was noted in four patients with no activation in the early days after stroke, whereas good clinical recovery was observed in eight patients with a normal activation pattern in the primary sensory motor area in the acute phase. In two patients BOLD activation correlated weakly with clinical recovery. Findings from TMS and DTI partially correlated with clinical recovery and functional scores. CONCLUSIONS: Clinically relevant insights into the "functional reserve" of stroke patients gained with peripheral nerve stimulation during fMRI may carry prognostic value already in the acute period of a cerebrovascular accident. SIGNIFICANCE: BOLD activation maps could provide insights into the functional organization of the residual systems and could contribute to medical decision making in neurological and rehabilitative treatment.


Assuntos
Estimulação Elétrica , Nervo Mediano/fisiopatologia , Oxigênio/sangue , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , Estimulação Magnética Transcraniana
12.
J Cardiovasc Surg (Torino) ; 52(3): 395-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18948867

RESUMO

A 49-year-old operated for aortic coartaction patient presented with thoracic and ascending aortic aneurysm. He was asymptomatic. Angio-magnetic resonance nuclear scan and angiography revealed an ascending aortic aneurysm (5.2 cm), bicuspid aortic valve, 6-cm proximal descending aortic pseudoaneurysm at the site of the previous operation with involvement of the left subclavian artery. Restenosis at the original site of coarctation and aortic arch hypoplasia distally to the brachiocefalic trunk was also found. The operation performed was a "modified Bentall - De Bono". The pseudoaneurysm was not accessible through median sternotomy due to the massive lung adhesions following the previous surgery. The left common carotid artery was explanted from the aortic arch and connected with a graft to the ascending aortic conduit. A proximal neck suitable for landing zone of the endovascular stent-graft was then established. The postoperative course was uneventful. After two weeks, the patient was readmitted. The exclusion of the thoracic descending aortic pseudoaneurysm by endovascular implantation of the stent-graft prosthesis was performed. The left subclavian artery was excluded because left vertebral artery was closed. The patient did not develop hand claudicatio. The procedure was successful.


Assuntos
Falso Aneurisma/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Coartação Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/etiologia , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Artéria Carótida Primitiva/cirurgia , Procedimentos Endovasculares/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Stents , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Clin Microbiol Infect ; 16(6): 640-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19732081

RESUMO

As proviral human immunodeficiency virus type 1 (HIV-1) DNA can replenish and revive viral infection upon activation, its detection might offer significant therapeutic information, complementing the input provided by plasma RNA determination in the follow-up of infected individuals. A selected group of acutely infected subjects was studied to verify both total and 2-long terminal repeat (2-LTR) DNA proviral load during the acute phase of infection and thereafter. Patients were divided in two sex- and age-matched groups: 19 naive individuals who did not receive antiretroviral therapy during the observation period and 20 subjects treated according to current guidelines. Total and 2-LTR HIV-1 DNA proviral load, in addition to RNA viral load and CD4 cell count, were determined in peripheral blood mononuclear cells (PBMC) at baseline, 6 and 12 months after the first sampling. Total and 2-LTR HIV-1 DNA proviral load exhibited no significant variation at any time in the naive patients (total HIV-1 DNA ranging from 896 + or - 731 to 715 + or - 673 copies/10(5) PBMC and 2-LTR HIV-1 DNA ranging from 94 + or - 105 to 65 + or - 44 copies/10(5) PBMC), whereas a significant reduction in both total HIV-1 DNA (ranging from 997 + or - 676 to 262 + or - 174 copies/10(5) PBMC) and 2-LTR HIV-1 DNA proviral load (ranging from 116 + or - 55 to 26 + or - 35 copies/10(5) PBMC) was detected in highly active antiretroviral therapy (HAART) patients, together with a CD4(+) T cell count increase and RNA load decrease. HAART negatively affects both the labile HIV burden and the integrated proviral DNA, at least in the initial period of successful treatment, suggesting that quantification of HIV-1 DNA proviral load may be an important parameter in monitoring HIV infection.


Assuntos
Fármacos Anti-HIV/uso terapêutico , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Provírus/isolamento & purificação , Carga Viral , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Provírus/genética , RNA Viral/sangue , Virologia/métodos
14.
Neuroradiol J ; 21(6): 745-54, 2009 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-24257042

RESUMO

Conventional MRI shows the morphology of the corpus callosum (CC), but does not reveal cortical connectivity or structural information on the CC. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to incorporate cortical connectivity information on the CC in 40 subjects and to detect the main area and sex structural differences. CC parcellation was based on trajectories to different cortical (prefrontal, frontal motor/premotor/supplementary motor connections, parieto-occipital, temporal) and sub-cortical areas (capsular/basal ganglia connections). In agreement with recent DTI studies, we found that motor fibers occupy a much larger portion of the CC than previously believed on the basis of anatomical data. Differences in anisotropy values were instead in agreement with previous morphological evidence of smaller fibers in the anterior and posterior portions of the CC. The main sex difference was observed in anisotropy values in frontal fibers that proved to be lower in females than in males. Statistically significant differences in the regional diffusion parameters and between sexes give rise to many important questions regarding fiber organization patterns, CC microstructure and the functional relevance of these differences and provide evidence for the role of DTI, which reaches beyond the information given by morphological analysis.

15.
Neuroradiol J ; 21(2): 159-65, 2008 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24256820

RESUMO

We performed functional magnetic resonance imaging (fMRI) in a 30-year-old man with idiopathic partial epilepsy with occipital spikes whose scalp EEG activity was characterized by persistent epileptiform discharges on eye closure, ceasing upon eye opening. We compared BOLD activation in the patient and in a control group of three normal volunteers. f-MRI showed that occipital cortex and frontal areas were activated in relation to eye movement in normal subjects during eye opening but not during eye closing. While persistent interictal spike and wave activity was present over the posterior and anterior scalp in the patient upon eye closing, f-MRI showed bilateral activation of the parietal and temporal regions. This fMRI study documents the activation of posterior and temporal areas related to continuous intercritical spikes evoked by eye closure, which are diffuse over the scalp. This activation was absent in the control group during eye closure.

17.
Neurol Sci ; 26(1): 55-6, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15877190
18.
Med Oncol ; 22(1): 45-56, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15750196

RESUMO

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8-2.0 Gy. The indications for radiosurgery were tumor volume <20 cm3, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with 1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.


Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias Embrionárias de Células Germinativas/secundário , Radiocirurgia/métodos , Neoplasias Testiculares/patologia , Adolescente , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia
19.
Neurol Sci ; 24(1): 40-3, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12754657

RESUMO

A case of symptomatic syringomyelia which appeared six years after Listeria meningoencephalitis is described. Chronic spinal arachnoiditis, as shown by standard MRI and dynamic phase contrast (PC) cine-MRI, may occur after spinal infection and is likely the cause of syringomyelia. To our knowledge, there are no previous reports of delayed spinal complications following Listeria monocytogenes infection. The possibility of developing syringomyelia should be always considered in any patient with a history of central nervous system infection.


Assuntos
Meningite por Listeria/diagnóstico , Siringomielia/diagnóstico , Alcoolismo/complicações , Humanos , Meningite por Listeria/tratamento farmacológico , Pessoa de Meia-Idade , Medula Espinal/microbiologia , Medula Espinal/patologia , Siringomielia/tratamento farmacológico
20.
Inhal Toxicol ; 15(4): 343-56, 2003 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-12635003

RESUMO

Surfactant lipids of the alveolar space protect the lung from various environmental stimuli. We investigated the influence of ultrafine (UF) CdO particles inhalation on two key enzymes involved in lung sphingolipid metabolism, serine palmitoyltransferase (SPT), and sphingomyelinase (SMase). Rats inhaled either 0.63 mg UF-CdO/m(3) for 6 h (group 1), or 1.08 mg UF-CdO/m(3) 12 h/day for 10 days (group 2). Two corresponding control groups inhaled filtered clean air. Additional rats intratracheally instilled with lipopolysaccharide (LPS) were used as positive controls. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) of lung tissue showed a significant increase in the level of SPT mRNA (LCB2 subunit) expression in group 2 compared to the corresponding controls (p <.01). Group 1 and LPS were not statistically different from control. No alteration in the mRNA level of SMase was detected in any exposure group. The immunohistochemical analysis showed that SPT (LCB2 subunit) localization was stronger in the alveolar type II cells of group 2 lungs compared to the corresponding controls. These results were correlated with alterations in BALF cellular and biochemical parameters and lung morphology. Since SPT is the key enzyme for de novo sphingolipid synthesis in lung surfactant and SMase is responsible for sphingomyelin catabolism, we can postulate that high-dose UF-CdO exposure for 10 days induces an increase in sphingolipid synthesis in the type II cells of rat lungs that would not be promptly followed by its degradation.


Assuntos
Aciltransferases/metabolismo , Compostos de Cádmio/administração & dosagem , Compostos de Cádmio/efeitos adversos , Glicoesfingolipídeos/biossíntese , Pulmão/enzimologia , Pulmão/patologia , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Esfingomielina Fosfodiesterase/efeitos dos fármacos , Esfingomielina Fosfodiesterase/metabolismo , Aciltransferases/análise , Aciltransferases/fisiologia , Administração por Inalação , Aerossóis , Análise de Variância , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Glicoesfingolipídeos/fisiologia , Imuno-Histoquímica , Lipopolissacarídeos/administração & dosagem , Tamanho do Órgão , Tamanho da Partícula , Alvéolos Pulmonares/enzimologia , Alvéolos Pulmonares/fisiopatologia , Proteínas Associadas a Surfactantes Pulmonares/análise , DNA Polimerase Dirigida por RNA/metabolismo , Ratos , Ratos Endogâmicos F344 , Serina C-Palmitoiltransferase , Fatores de Tempo
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