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BACKGROUND: Disseminated non-tuberculous mycobacteria (dNTM) infections are mostly reported among individuals with an underlying congenital or acquired immunodeficiency or receiving immunosuppressive treatment, but are rarely documented in otherwise healthy subjects. CASE PRESENTATION: We describe a case of recurrent disseminated mycobacterial infection in an apparently immunocompetent Chinese woman. Mycobacterium szulgai and Mycobacterium avium-complex were identified in distinct episodes. Long-term antimycobacterial therapy was administered given the occurrence of recurrent events when off-treatment. Successful management over more than 10 years and immunologic data are reported. CONCLUSIONS: This case-report highlights that dNTM should be suspected also among apparently immunocompetent hosts and that thorough assessment of underling immune-impairments is helpful to define patients' management. Long-term antimycobacterial therapy and close monitoring is required to grant successful outcomes in case of recurrent dNTM infections.
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Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Recidiva , Humanos , Feminino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Antibacterianos/uso terapêutico , Complexo Mycobacterium avium/efeitos dos fármacos , China , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , População do Leste AsiáticoRESUMO
Nontuberculous mycobacteria are a rare but still emerging cause of difficult-to-treat prosthetic joint infection. To our knowledge only 17 cases of M. abscessus complex prosthetic joint infection are reported in literature, of which only 1 is by M. abscessus subps. abscessus. No guidelines are available for this clinical scenario. We describe a 68-years-old female patient with an early-onset M. abscessus subsp. abscessus prosthetic joint infection, successfully treated with a tailored medical-surgical strategy, and present an overview of cases currently available in the literature to assist physicians in the management of these uncommon infections.
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Abstract: Migrants have accounted for more than 40% of new HIV diagnoses in Europe in 2022. Among the population of asylum seekers currently present in the Trento Province, screening for HIV infection is poorly carried out for various reasons. Here we report our experience about screening for HIV infection in asylum seekers present in that area using rapid self HIV-testing.
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Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-Aspergillus invasive mold diseases. Here, we perform a narrative review, discussing the major advances of the last decade on prophylaxis, the diagnosis of and the treatment of IFDs in patients with high-risk neutropenic fever undergoing remission induction chemotherapy for AML/MDS and allo-HSCT. Then, we present our single-center retrospective experience on b-IFDs in 184 AML/MDS patients undergoing high-dose chemotherapy while receiving posaconazole (n = 153 induction treatments, n = 126 consolidation treatments, n = 60 salvage treatments). Six cases of probable/proven b-IFDs were recorded in six patients, with an overall incidence rate of 1.7% (6/339), which is in line with the literature focused on MAP with azoles. The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug-drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs' risk stratification), and new antifungals and their features (rezafungin and olorofim).
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West Nile Virus infections has become endemic in various locations around the world. Symptomatic cases manifest as an acute febrile illness and in less than 1% with neuroinvasive manifestations. We report one of the very few cases of probable WNV-mediated isolated hepatitis to shed light on a possibly underestimated clinical picture.
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Doenças Cardiovasculares , Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , Fatores de Risco , DNARESUMO
A new amperometric immunosensor for 2,4,6-trinitrotoluene based on the working principle of competitive enzyme-linked immunosorbent assay was developed and characterised. An electrodeposited nanogold substrate was functionalised by deposition of self-assembled monolayers of 2-aminoethanethiol as linkers for the subsequent immobilisation of polyamidoaminic dendrimers. Our approach makes use of those dendrimers to anchor a trinitrobenzene-ovalbumin conjugate on the electrode surface. The immunosensor was tested and validated for the determination of 2,4,6-trinitrotoluene showing high selectivity with respect to other nitroaromatic compounds, a limit of detection of 4.8 ng/mL and a limit of quantitation of 6 ng/mL. The immunosensor was tested for the quantification of the analyte in spiked soils and in a real sample of post-blast soil, evidencing a good recovery rate (113 %).
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Técnicas Biossensoriais/métodos , Ovalbumina/química , Poluentes do Solo/análise , Trinitrotolueno/análise , Técnicas Biossensoriais/instrumentação , Dendrímeros/química , Ouro/química , Nanopartículas Metálicas/químicaRESUMO
Melanoma progression is favoured by prevalence, within the micro-environment of primary cutaneous melanoma, of suppressive forces, e.g. exerted by CD4(+) CD25(+) FOXP3(+) regulatory T lymphocytes, over anti-melanoma immunity, e.g. exerted by CD8(+) cytolytic T lymphocytes. The CD27 glycoprotein is crucial because it is able to identify regulatory T cells endowed with strong suppressive ability, whilst CD8(+) T cells endowed with actual cytolytic ability become CD27(-). The present in situ quantitative immunohistochemical study, including a series of double labelling experiments and morphometrical cell analyses, shows that the vast majority of lymphocytes infiltrating primary cutaneous melanoma express CD27. Specifically, virtually the entire CD4(+) CD25(+) FOXP3(+) T subset infiltrating primary cutaneous melanoma also co-expressed CD27; CD27 was, moreover, co-expressed even by the vast majority of the CD8(+) T cells, and, conversely, effector/cytotoxic CD8(+)CD27(-) cells were very scarcely represented. The overwhelming CD27 co-expression may confer on the CD4(+)CD25(+)FOXP3(+) T subset a consistent capacity to suppress anti-melanoma immunity, whereas the too low CD8(+) CD27(-) cell proportion may presumably be insufficient to confer on the CD8(+) T subset a satisfactory anti-melanoma cytotoxic activity. We therefore propose that these CD27-discriminated pathways may trigger a functional imbalance within the microenvironment of primary cutaneous melanoma, thus favouring melanoma progression.
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Progressão da Doença , Linfócitos do Interstício Tumoral/metabolismo , Melanoma/patologia , Neoplasias Cutâneas/patologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Dermatite/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Subpopulações de Linfócitos/metabolismo , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Linfócitos T Reguladores/metabolismoRESUMO
The development of a voltammetric immunosensor for determination of alpha-fetoprotein (AFP) in serum is presented. ELISA assays with voltammetric reading were carried out exploiting the peculiar properties of nanobiocomposite materials based on gold nanoparticles for the immobilization of Antibody (Ab)/Antigen/Antibody-HRP (Horseradish Peroxidase) sandwich on the glassy carbon (GC) electrode surface. The electrochemical transduction was mediated by thionin, which was used in its monomeric form dissolved in the reading solution, so avoiding critical immobilization procedures. The study was aimed at the development and validation of an immunosensor able to provide results in short time, simple to use, rugged and cost-effective for AFP monitoring purposes. A crucial aspect of the study was the development of an experimental protocol leading to highly standardized and consequently reproducible sensors. Two-way analysis of variance (ANOVA) was applied to study the effect of the concentration of the solutions used for the incubation of the antibodies. The sensor was validated in serum assessing stability of the immunocomplex, linearity of response, limit of detection (3.7 ng/ml) and limit of quantitation (11 ng/ml), precision (intra- and inter-sensor repeatability) and recovery rate (103%). The stability of the GC/Ab functionalized substrate was demonstrated over one month, showing variation coefficients below 5%. Experiments carried out with real samples of clinical interest evidenced that the developed immunosensor can be considered as powerful tool in cancer screening programmes.
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Técnicas Biossensoriais/instrumentação , Condutometria/instrumentação , Imunoensaio/instrumentação , Nanoestruturas/química , Nanotecnologia/instrumentação , alfa-Fetoproteínas/análise , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Nanoestruturas/ultraestruturaRESUMO
Although tumor-infiltrating lymphocytes (TILs) of primary cutaneous melanoma (PCM) include cytolytic T cells able to exert anti-PCM immunity, progression of PCM most frequently occurs, raising the hypothesis that the PCM microenvironment may also exert suppressive forces, for example, possibly developed by regulatory T (T(REG)) lymphocytes. The aim of this study was to investigate whether TILs of PCMs include lymphocytes bearing the transcription factor forkhead box protein P3 (FOXP3), which is the T(REG) lineage specification molecule in mice, and is debated to have a similar role in humans. Fourteen patients with PCM were selected, of which four had radial growth phase (RGP) stage I melanoma, five had vertical growth phase (VGP) stage I melanoma, and five had VGP stage III-IV melanoma. Formalin-fixed, paraffin-embedded sections were utilized for immunohistochemical single and double stainings. TILs of PCMs included FOXP3-bearing lymphocytes, which predominantly were CD20- and CD8-negative, but CD3-, CD4-, and CD25-positive, thus consistent with the standard immunophenotypical characteristics of "natural" T(REG) cells. Further, the proportions of FOXP3-bearing lymphocytes were higher in vertical than in RGP (P=0.001), as well as in late than in early melanoma stages (P<0.001). Should these FOXP3-bearing lymphocytes actually exert regulatory capabilities within the PCM microenvironment, they may suppress "in vivo" the local anti-PCM immune response, thus favoring melanoma progression.
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Fatores de Transcrição Forkhead/metabolismo , Melanoma/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Cutâneas/patologia , Subpopulações de Linfócitos T/patologia , Biomarcadores/metabolismo , Linhagem da Célula/imunologia , Progressão da Doença , Humanos , Imunofenotipagem , Melanoma/imunologia , Melanoma/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologiaRESUMO
A new NIR method based on multivariate calibration for determination of ethanol in industrially packed wholemeal bread was developed and validated. GC-FID was used as reference method for the determination of actual ethanol concentration of different samples of wholemeal bread with proper content of added ethanol, ranging from 0 to 3.5% (w/w). Stepwise discriminant analysis was carried out on the NIR dataset, in order to reduce the number of original variables by selecting those that were able to discriminate between the samples of different ethanol concentrations. With the so selected variables a multivariate calibration model was then obtained by multiple linear regression. The prediction power of the linear model was optimized by a new "leave one out" method, so that the number of original variables resulted further reduced.
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The thioamido function of [CuCl2(1H)]Cl (2) (1=4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole), a cytotoxic copper complex, was converted into thioether moieties, leading to the synthesis of [CuCl2(3)]2 (4) and [CuCl2(5)] (6) (3=6-methyl-3-pyridin-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine; 5=4-amino-5-ethylthio-3-(2-pyridyl)-1,2,4-triazole). These complexes were structurally characterized, and their stability constants, along with their biological activity, were determined. 4 and 6 were slightly less stable and significantly less active than 2. However, as 2, both complexes induced nonapoptotic vacuolar cell death. Copper uptake, investigated in both 2-sensitive and -insensitive cell types, was markedly higher in sensitive cells where it was associated with an increase in oxidized glutathione. These data suggest that the thioamido function enhances the cytotoxicity of copper complexes in cancer cells promoting the accumulation of the metal and its interaction with cell thiols.
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Antineoplásicos/síntese química , Quelantes/química , Cobre , Compostos Organometálicos/síntese química , Triazóis/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologiaRESUMO
Dinuclear Cu(I) complexes with bifunctionalized homoscorpionate ligands, hydrotris(thioxotriazolyl)borato [Li(Tr(Me,o)(-)(Py)) (1) and Li(Tr(Mes,Me)) (2)], and the heteroscorpionate ligand hydro[bis(thioxotriazolyl)-3-(2-pyridyl)pyrazolyl]borato [K(Br(Mes)pz(o)(-)(Py))] (3) were synthesized and crystallographically characterized. The complexes [Cu(Tr(Mes,Me))](2) (4) and [Cu(Tr(Me,o)(-)(Py))](2) (5) exhibit a similar coordination geometry where every metal is surrounded by three thioxo groups in a trigonal arrangement. The presence of a [B-H...Cu] three-center-two-electron interaction in both compounds causes the overall coordination to become tetrahedrally distorted (S(3)H coordination for each metal). The complex [Cu(Br(Mes)pz(o)(-)(Py))](2) (6) presents a trigonal geometry in which the metals interact with two thioxo groups and a bridging pyrazolyl nitrogen atom. A weak contact with a pyridine nitrogen atom completes the coordination of the metals (S(2)N,N' coordination for each metal). [Cu(Tr(Mes,Me))](2), [Cu(Tr(Me,o)(-)(Py))](2), and [Cu(Br(Mes)pz(o)(-)(Py))](2) exhibit fluxional behavior in solution as evidenced by variable-temperature NMR spectroscopy, and for 5 and 6 two species in equilibrium [in the ratio 2/1 for 5 (CDCl(3)) and 3/2 for 6 (CD(2)Cl(2))] are distinguishable in the (1)H NMR spectra at 270 K. 2D-NOESY spectra recorded at 270 K assisted in the attribution of solution molecular geometries for each isomer of 5 and 6. The free energy of activation (DeltaG()(Tc)) was determined for both equilibria from the evaluation of the coalescence temperature. DFT calculations were performed to describe plausible molecular geometry for the minor isomer of 5 and 6 and to propose a possible mechanism of interconversion between major and minor isomers. Cyclic voltammograms were recorded in CH(2)Cl(2) (3 and 6) or CH(2)Cl(2)/CH(3)CN (1/1, v/v) (2, 4, and 5) solutions using 0.1 M TBAHFP or TBAOTf as supporting electrolytes. [Cu(Tr(Mes,Me))](2), [Cu(Tr(Me,o)(-)(Py))](2), and [Cu(Br(Mes)pz(o)(-)(Py))](2) exhibit a quasi-reversible Cu(I)/Cu(II) redox behavior with E(pa) = +719 mV and E(pc) = +538 mV for 4, E(pa) = +636 mV and E(pc) = -316 mV for 5, and E(pa) = +418 mV and E(pc) = -319 mV for 6.
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In this paper, the preliminary results of a study on concentration of heavy metals in PM2.5 (atmospheric particles with aerodynamic diameter less than 2.5 microm) fractions of atmospheric particulate matter, sampled in Milan, are presented. This work aims to develop an electroanalytical method to analyse Pb, Cu, Cd and Ni in PM2.5 and to investigate seasonal and weekly trends in the amount of PM2.5 and its composition for considered metals. The samples have been selected within the seasons ranging from September 2002 to November 2003 so that they represent the possible seasonal changes; the samples within this period have been chosen in order to have data relevant to both working days and holidays. The determination of Cd, Pb and Cu has been carried out by Differential Pulse Anodic Stripping Voltammetry, whereas the concentration of Ni has been determined by Differential Pulse Adsorptive Cathodic Stripping Voltammetry. The concentrations of the metals in the sampled atmosphere and in the PM2.5 have been evaluated; through ANOVA possible seasonal or weekly variations in the above cited concentrations have been investigated.
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Poluentes Atmosféricos/química , Monitoramento Ambiental , Metais Pesados/análise , Atmosfera , Cádmio/análise , Cobre/análise , Itália , Chumbo/análise , Níquel/análise , Estações do Ano , População UrbanaRESUMO
The formation of non-absorbing complexes in an organic phase has been exploited for the spectrophotometric determination of ionic analytes in aqueous solutions. The method is based on liquid-liquid extraction of aqueous solution with lipophylic organic phases containing an acid-base chromoionophore, a neutral lypophilic ligand (neutral carrier) selective to the analyte and a cationic (or anionic) exchanger. The method avoids all difficulties of the preparation of the very thin membranes used in optodes, so that it can advantageously be used for the study of the role physical-chemical parameters of the system in order to optimize them and to prepare, if necessary, an optimized optode. Two lipophylic derivatives of Nile Blue and 4',5-dibromofluorescein have been synthesized, in order to ensure their permanence within organic phase. Two different neutral carriers previously characterized by us as ionophores for liquid-membrane Ion Selective Electrodes have been employed. Three different ionic exchangers have been tested. Furthermore, a model allowing the interpolation of experimental data and the determination of the thermodynamic constant of the ionic-exchange equilibrium has been developed and applied.
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Eletrólitos/análise , Espectrofotometria/métodos , Troca Iônica , Ionóforos , Solventes , Termodinâmica , Água/químicaRESUMO
BACKGROUND: Fas ligand (Fas-L), which is expressed by melanoma cells, can be cleaved from cell membranes and become soluble (soluble Fas-L, sFas-L). No previous study examined sFas-L levels in patients affected with all clinical stages of melanoma. OBJECTIVE: To investigate if sFas-L can be considered a serological marker for melanoma. METHODS: Serological sFas-L values in 114 patients with melanoma and 25 controls were measured by using ELISA. RESULTS: sFas-L values in patients were not significantly higher than in controls. They were not significantly different, moreover, when patient groups belonging to different clinical stages were compared with the control group. Two patients affected with distant metastases had the highest sFas-L values. CONCLUSION: sFas-L cannot be considered, within the limits of this study, as a serological marker for the detection of melanoma. Further studies are needed to evaluate whether sFas-L can be used as a marker for disease progression and/or prediction of therapy outcome.
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Biomarcadores Tumorais/sangue , Melanoma/diagnóstico , Glicoproteínas de Membrana/sangue , Neoplasias Cutâneas/diagnóstico , Receptor fas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Criança , Ensaio de Imunoadsorção Enzimática , Proteína Ligante Fas , Feminino , Humanos , Masculino , Melanoma/sangue , Pessoa de Meia-Idade , Neoplasias Cutâneas/sangueRESUMO
BACKGROUND: Recurrences of cervical lesions associated with human papillomavirus are more frequent in HIV-infected (HIV+) than in HIV- women. Recurrences of external genital warts were investigated in HIV+ patients and HIV- control subjects. GOAL: To compare relapses after treatment of external genital warts between HIV+ and HIV- patients. STUDY DESIGN: At the sexually transmitted disease (STD) center in Brescia, Italy, 1336 patients (241 HIV+ and 1095 HIV-) with external genital warts were examined in the decade 1990 to 1999. Various local treatments were used. RESULTS: Treatments generally triggered recovery from the lesions. The relapses observed up to 1 year after the response, examined by survival analysis, were significantly (P < 0.001) more frequent in the HIV+ (160 cases; 66.4%) than in the HIV- (294 cases; 26.8%) subjects. Multiple relapses observed up to 1 year after treatment occurred in 69 of 241 HIV+ patients, as compared with 14 of 1095 HIV- control subjects (P < 0.001). CONCLUSION: According to the study findings, HIV infection can be considered a risk factor for the development and recurrence of external genital warts. Multiple relapses should drive patients to HIV testing.
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Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Condiloma Acuminado/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Adulto , Estudos de Casos e Controles , Condiloma Acuminado/etiologia , Condiloma Acuminado/terapia , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de RiscoRESUMO
A new interpretative model for interpolation of potentiometric data from liquid membrane ion selective electrodes has been formulated; the model allows one to achieve information about partitioning equilibria establishing at the membrane-analysed solution interface of hydrophilic cations present in the membrane as counterions of exchanger lipophylic anions. The fundamental importance of such equilibria is related to their contribution to the detection limit of the electrodes. The soundness of the proposed model was positively verified by employing it in the characterization of new K(+)-selective electrodes based on a calixarenic ionophore. Although the validity of interpolation based on our model does not significantly differ from that obtained with the simpler model providing the inclusion of a constant parameter in the logarithmic argument of Nicolski-Eisenman's equation, the information obtained resulted to be analytically suitable for optimising the membrane composition and, as a consequence, the performance of the electrodes.