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1.
Graefes Arch Clin Exp Ophthalmol ; 259(8): 2157-2165, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33523252

RESUMO

BACKGROUND: Systemic vascular involvement in COVID-19 has been identified in several patients: not only endothelial derangement and increased permeability are reported to be early hallmarks of organ damage in patients with COVID-19 but are also the most important cause of worsening of clinical conditions in severe cases of SARS-CoV-2 infection. There are several reasons to hypothesize that the eye, and the retina in particular, could be a target of organ damage in SARS-CoV-2 infection. METHODS: This cohort observational study analyzes OCT angiography and structural OCT of 70 post-COVID-19 patients evaluated at 1-month hospital discharge and 22 healthy control subjects. Primary outcomes were macular vessel density (VD) and vessel perfusion (VP); structural OCT features were evaluated as secondary outcomes. In addition, patients and healthy volunteers were evaluated for best corrected visual acuity, slit lamp photograph, and fundus photo image. RESULTS: VD and VP in 3 × 3 and 6 × 6 mm scans for SCP and DCP showed no significant differences between the groups. Similarly, CMT and GCL did not reveal significant differences between post-COVID-19 and healthy patients. Nine patients (12.9%) featured retinal cotton wool spots and 10 patients had vitreous fibrillary degeneration. The prevalence of epiretinal membrane and macular hole was similar in the two groups. One case of extra papillary focal retinal hemorrhage was reported in the post-COVID-19 group. CONCLUSIONS: Macula and perimacular vessel density and perfusion resulted unaltered in mild post-COVID-19 patients at 1-month hospital discharge, suggesting no or minimal retinal vascular involvement by SARS-CoV-2.


Assuntos
COVID-19 , Angiofluoresceinografia , Humanos , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , SARS-CoV-2 , Tomografia de Coerência Óptica , Acuidade Visual
2.
J Proteome Res ; 19(1): 64-74, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31621329

RESUMO

The aim of this proof-of-concept, pilot study was the evaluation of the effects of steroid administration and suspension of an inhaled corticosteroid (ICS)-long-acting ß2-agonist (LABA) extrafine fixed dose combination (FDC) on metabolomic fingerprints in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that a comprehensive metabolomics approach discriminates across inhaled pharmacotherapies and that their effects on metabolomic signatures depend on the biological fluids analyzed. We performed metabolomics via nuclear magnetic resonance (NMR) spectroscopy in exhaled breath condensate (EBC), sputum supernatants, serum, and urine. Fourteen patients suffering from COPD who were on regular inhaled fluticasone propionate/salmeterol therapy (visit 1) were consecutively treated with 2-week beclomethasone dipropionate/formoterol (visit 2), 4-week formoterol alone (visit 3), and 4-week beclomethasone/formoterol (visit 4). The comprehensive NMR-based metabolomics approach showed differences across all pharmacotherapies and that different biofluids provided orthogonal information. Serum formate was lower at visits 1 versus 3 (P = 0.03), EBC formate was higher at visit 1 versus 4 (P = 0.03), and urinary 1-methyl-nicotinamide was lower at 3 versus 4 visit (P = 0.002). NMR-based metabolomics of different biofluids distinguishes across inhaled pharmacotherapies, provides complementary information on the effects of an extrafine ICS/LABA FDC on metabolic fingerprints in COPD patients, and might be useful for elucidating the ICS mechanism of action.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Corticosteroides/uso terapêutico , Quimioterapia Combinada , Fumarato de Formoterol/uso terapêutico , Humanos , Espectroscopia de Ressonância Magnética , Metabolômica , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
3.
Anticancer Drugs ; 31(1): 67-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633499

RESUMO

Cytarabine, the 4-amino-1-(ß-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.


Assuntos
Citarabina/química , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/economia , Cromatografia Líquida de Alta Pressão , Redução de Custos , Citarabina/administração & dosagem , Citarabina/economia , Custos de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Adesão à Medicação , Ressonância Magnética Nuclear Biomolecular/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Soluções/química
4.
Int J Mol Sci ; 21(23)2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33276425

RESUMO

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.


Assuntos
Extratos Vegetais/farmacologia , Serenoa/química , Urtica dioica/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico
5.
J Sep Sci ; 41(7): 1548-1557, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29282870

RESUMO

Humulus lupulus L. (hop) is highly interesting from a nutraceutical perspective. The hop phytocomplex contains a wide range of bioactive metabolites, and its characterization is challenging. To tackle such a task, for the first time we applied and compared a combined approach consisting of online comprehensive two-dimensional liquid chromatography with tandem mass spectrometry and direct infusion Fourier transform ion cyclotron mass spectrometry. A reversed phase × reversed phase approach with a shifted gradient in the second dimension ensured selectivity and two-dimensional space coverage. Hyphenation with an ion trap time-of-flight analyzer led to the identification of 83 compounds in 70 min, comprising a novel quercetin derivative and six unknown bitter acids. On the other hand, the direct infusion method was able to identify 40 analytes (except isomers) with high mass accuracy (≤ 0.1 ppm) in less than 1 min analysis time. The developed approach can be used in a complementary way, combining the separation capability and high informative spectra of two-dimensional liquid chromatography tandem mass spectrometry with the ultra-high mass accuracy of direct infusion, for potential compound discovery or the accurate profiling of bioactive compounds in different hop cultivars as well as for monitoring processing and storage of hop-based products.


Assuntos
Humulus/química , Internet , Extratos Vegetais/análise , Quercetina/análise , Cromatografia Líquida , Espectrometria de Massas , Estrutura Molecular , Espectrometria de Massas em Tandem
6.
J Sep Sci ; 40(10): 2188-2197, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28349602

RESUMO

In this study, an improved online comprehensive two-dimensional liquid chromatography platform coupled to tandem mass spectrometry was developed for the analysis of complex polyphenolic samples. A narrowbore hydrophilic interaction chromatography column (150 × 2.0 mm, 3.0 µm, cross-linked diol) was employed in the first dimension, while a reversed-phase column based on monodisperse sub-2 µm fully porous particles (50 × 3.0 mm, 1.9 µm d.p.) with high surface area (410 m2 /g) was employed in the second dimension. The combination of a trapping column modulation interface with the high retentive fully porous monodisperse reversed-phase column in the second dimension resulted in higher peak capacity values (1146 versus 867), increased sensitivity, sharper and more symmetrical peaks in comparison with a conventional loop-based method, with the same analysis time (70 min). The system was challenged against a complex polyphenolic extract of a typical Italian apple cultivar, enabling the simultaneous separation of multiple polyphenolic classes, including oligomeric procyanidins, up to degree of polymerization of 10. Hyphenation with an ion trap time-of-flight mass spectrometer led to the tentative identification of 121 analytes, showing how this platform could be a powerful analytical tool for the accurate profiling of complex polyphenolic samples.

7.
Phytochem Anal ; 28(6): 521-528, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28686312

RESUMO

INTRODUCTION: Clonal selection and hybridisation are valid strategies to obtain fruits with enhanced sensorial and nutraceutical properties. Within Citrus sinensis varieties, Tarocco clone "Lempso" is a typical product of the Calabria region (Italy) characterised by its red pulp. This is the first report concerning its accurate profiling. OBJECTIVE: To characterise in detail the flavonoid composition of Lempso clone and to compare its antioxidant potential with other Citrus varieties by a fast screening method. METHODOLOGY: Extracts were subjected to solid phase extraction and the qualitative/quantitative profile was elucidated through ultra-high performance liquid chromatography (UHPLC) coupled to photodiode array (PDA) and ion trap time-of-flight (IT-TOF) mass spectrometry detection, and compared to both Cleopatra mandarin (Citrus reticulata) and blood orange (Citrus sinensis (L.) Osbeck) Sanguinello varieties. The antioxidant activity was assessed by pre-column 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reaction coupled to UHPLC-PDA. RESULTS: Lempso is characterised by flavonoids (17) and anthocyanins (8). Flavanones content (Hesperidin: 57.19 ± 0.49, Vicenin-2: 4.59 ± 0.03, Narirutin: 5.78 ± 0.13 mg/100 mL) was considerably higher than Cleopatra and Sanguinello varieties. The developed DPPH-UHPLC-PDA method provides information regarding the single contributions to antioxidant activity, highlighting how Ferulic acid, Quercetin and Cyanidin derivatives possess considerable radical scavenging activity (> 50%). The total antioxidant activity was also evaluated and compared with positive controls, showing higher scavenging activity than Cleopatra and Sanguinello (IC50 : 333.76 ± 10.81 µg/mL vs. 452.62 ± 10.81 and 568.39 ± 26.98 µg/mL, respectively). CONCLUSION: These data evidence the nutraceutical potential of Lempso variety, which could be an ingredient for functional beverages. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Antioxidantes/química , Cromatografia Líquida de Alta Pressão/métodos , Citrus sinensis/química , Flavonoides/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Antocianinas/química , Flavonoides/metabolismo , Processos Fotoquímicos , Fatores de Tempo
8.
Molecules ; 22(4)2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28420125

RESUMO

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrussinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value.


Assuntos
Citrus sinensis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios , Antioxidantes , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/biossíntese , Flavonoides/química , Flavonoides/farmacologia , Sucos de Frutas e Vegetais , Absorção Gastrointestinal , Heme Oxigenase-1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacocinética , Polifenóis/química , Polifenóis/farmacologia , Transporte Proteico , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral , Fator de Transcrição RelA/metabolismo
9.
COPD ; 13(3): 367-71, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26645660

RESUMO

Proper use of inhaler devices may be problematic in elderly patients due to age-related difficulties. A survey was administered to elderly patients to investigate the usability of the Genuair® device and patients' subjective viewpoint on the device. A representative sample of the Italian population aged ≥ 65 years was completed with a pre-defined sample of 89 patients with hand arthritis/arthrosis. Of 526 respondents, 88 were not self-sufficient. Only the replies of the 438 self-sufficient respondents were analyzed. A total of 107 participants (24%) reported having respiratory diseases, and 81 of these (76%) were users of inhaler devices. After the first test, the device was considered "practical/handy" by 90% of patients and "easy to use" by 89%. After the second test, in which patients received a demonstration of the correct inhalation maneuver, the percentage of patients scoring ≥ 7 increased to 93% for the first characteristic and was confirmed for the second, with no differences between the groups in terms of age, educational level, use of devices, and presence of arthritis/arthrosis. The mean time to explain the inhaler technique and to perform a correct inhalation was 1'38"± 1'37", and 70% of the respondents required less than 2 minutes, with no differences between the groups in terms of age, education level, use of devices, and presence of arthritis/arthrosis. In conclusion, Genuair® was well accepted and easy to use in a representative sample of the Italian population aged ≥ 65 years. These characteristics make it a valid choice in the elderly, thus enabling patients to better cope with the problems and difficulties that are common to this age group.


Assuntos
Artrite/complicações , Nebulizadores e Vaporizadores/normas , Educação de Pacientes como Assunto , Satisfação do Paciente , Idoso , Idoso de 80 Anos ou mais , Feminino , Mãos , Humanos , Itália , Masculino , Inquéritos e Questionários , Fatores de Tempo
10.
Eur J Nutr ; 52(1): 307-16, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22406906

RESUMO

PURPOSE: The metabolic syndrome (MetS) is highly prevalent in Western older populations. MetS is an intriguing entity, because it includes potentially reversible risk factors. Some studies have suggested an inverse correlation between MetS and health-related quality of life (HRQoL), but data regarding older subjects are scanty and conflicting. The aim of this study was to assess the association between HRQoL and MetS in older, unselected community-dwelling subjects. METHODS: We analyzed data of 356 subjects aged 75+ living in Tuscania (Italy). HRQoL was assessed using the Health Utilities Index, Mark 3. Diagnosis of MetS was defined according to the National Cholesterol Education Program's ATP-III criteria. RESULTS: MetS was reported by 137 (38%) participants. According to linear regression analysis, MetS was associated with significantly better HRQoL in men (B = 0.19 95% CI = 0.06-0.32; p = 0.006), but not in women. Also, when the regression model was analyzed in men, MetS was associated with better HRQoL (B = 0.17, 95% CI = 0.01-0.32; p = 0.035) only among participants aged 80+. No significant associations were found in men between HRQoL and any of the single components of MetS. CONCLUSIONS: MetS is not associated with worse HRQoL among community-dwelling elderly; it is associated with significantly better HRQoL among the oldest men.


Assuntos
Síndrome Metabólica/epidemiologia , Qualidade de Vida , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Modelos Lineares , Masculino , Análise Multivariada , Prevalência , Fatores Sexuais
11.
J Sep Sci ; 36(20): 3351-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23922323

RESUMO

We have developed a fast ultra HPLC with ion-trap TOF-MS method for the analysis of flavonoids in Citrus bergamia juice. With respect to the typical methods for the analysis of these matrices based on conventional HPLC techniques, a tenfold faster separation was attained. The use of a core-shell particle column ensured high resolution within the fast analysis time of only 5 min. Unambiguous determination of flavonoid identity was obtained by the employment of a hybrid ion-trap TOF mass spectrometer with high mass accuracy (average error 1.69 ppm). The system showed good retention time and peak area repeatability, with maximum RSD% values of 0.36 and 3.86, respectively, as well as good linearity (R(2) ≥ 0.99). Our results show that ultra HPLC can be a useful tool for ultra fast qualitative/quantitative analysis of flavonoid compounds in citrus fruit juices.


Assuntos
Bebidas/análise , Cromatografia Líquida de Alta Pressão/métodos , Citrus/química , Flavonoides/química , Espectrometria de Massas/métodos , Extratos Vegetais/química , Frutas/química , Estrutura Molecular
12.
Commun Biol ; 6(1): 1200, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001239

RESUMO

The source and roles of fibroblasts and T-cells during maladaptive remodeling and myocardial fibrosis in the setting of pulmonary arterial hypertension (PAH) have been long debated. We demonstrate, using single-cell mass cytometry, a subpopulation of endogenous human cardiac fibroblasts expressing increased levels of CD4, a helper T-cell marker, in addition to myofibroblast markers distributed in human fibrotic RV tissue, interstitial and perivascular lesions in SUGEN/Hypoxia (SuHx) rats, and fibroblasts labeled with pdgfrα CreERt2/+ in R26R-tdTomato mice. Recombinant IL-1ß increases IL-1R, CCR2 receptor expression, modifies the secretome, and differentiates cardiac fibroblasts to form CD68-positive cell clusters. IL-1ß also activates stemness markers, such as NANOG and SOX2, and genes involved in dedifferentiation, lymphoid cell function and metabolic reprogramming. IL-1ß induction of lineage traced primary mouse cardiac fibroblasts causes these cells to lose their fibroblast identity and acquire an immune phenotype. Our results identify IL-1ß induced immune-competency in human cardiac fibroblasts and suggest that fibroblast secretome modulation may constitute a therapeutic approach to PAH and other diseases typified by inflammation and fibrotic remodeling.


Assuntos
Coração , Hipertensão Arterial Pulmonar , Animais , Humanos , Camundongos , Ratos , Fibroblastos/metabolismo , Fibrose , Miofibroblastos/metabolismo
13.
Front Psychol ; 14: 1136667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492442

RESUMO

Background: COVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation. Methods: Individuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests. Results: A total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress. Conclusion: COVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

14.
Cancer Immunol Immunother ; 61(1): 31-40, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21833592

RESUMO

Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer. BCG therapy is the most successful example of immunotherapy in cancer. Unfortunately, the treatment-related side effects are still relevant. Furthermore, non-responder patients are candidate to radical cystectomy in the absence of valuable alternative options. These aspects have prompted the search for newer biological response modifiers (BRM) with a better benefit/side effects ratio. The toll-like receptor (TLR) 2 ligand, Helicobacter pylori protein HP-NAP, has been shown to deserve a potential role as BRM. HP-NAP is capable of driving the differentiation of T helper (Th) 1 cells, both in vitro and in vivo, because of its ability to create an IL-12-enriched milieu. Herein, we report that local administration of HP-NAP decreases tumour growth by triggering tumour necrosis in a mouse model of bladder cancer implant. The effect is accompanied by a significant accumulation of both CD4+ and CD8+ IFN-γ-secreting cells, within tumour and regional lymph nodes. Noteworthy, HP-NAP-treated tumours show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Our findings strongly indicate that HP-NAP might become a novel therapeutic "bullet" for the cure of bladder tumours.


Assuntos
Vacina BCG/farmacologia , Proteínas de Bactérias/farmacologia , Helicobacter pylori/imunologia , Células Th1/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Administração Intravesical , Animais , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Feminino , Humanos , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Células Th1/metabolismo , Neoplasias da Bexiga Urinária/patologia
15.
Aging Clin Exp Res ; 24(2): 145-51, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22842833

RESUMO

BACKGROUND AND AIMS: Although the use of angiotensin-converting enzyme-inhibitors (ACE-I) is a cornerstone of treatment for heart failure (HF), these agents have been associated with decreasing hemoglobin levels in several settings. The aim of this study was to assess whether ACE-I are associated with decreasing hemoglobin in older subjects, and whether this effect is enhanced among patients with HF. METHODS: The association between starting use of ACE-I and variations in hemoglobin levels was investigated in 10,354 hospitalized elderly, 1217 of whom had a verified diagnosis of HF, enrolled in a multicenter pharmacoepidemiology survey. RESULTS: According to Cox regression analysis, the relative risk of a decrease in hemoglobin levels >0.5 g/dL associated with starting treatment with ACE-I was 1.12 (95% CI 0.98-1.26, p=0.081) among participants without HF, and 1.98 (95% CI 1.54-2.53, p<0.0001) among patients with HF, after adjusting for potential confounders. Analysis of the interaction term in Cox regression confirmed that the association between use of ACE-I and hemoglobin decrease varied according to diagnosis of HF (p=0.003) and older age (p=0.029). CONCLUSIONS: Starting treatment with ACE-I is independently associated with increased risk of hemoglobin decrease among older hospitalized patients with HF. Hemoglobin levels should be monitored in older subjects who start ACE-I.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Hemoglobinas/metabolismo , Idoso , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Farmacoepidemiologia/métodos , Fatores de Risco
16.
Clin Geriatr Med ; 38(3): 593-603, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35868675

RESUMO

Coronavirus disease 2019 is known to impact older people more severely and to cause persistent symptoms during the recovery phase, including cognitive and neurologic ones. We investigated the cognitive and neurologic features of 100 elderly patients with confirmed diagnosis of coronavirus disease 2019 evaluated in the postacute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and 8 neuropsychological tests. Overall, a total of 33 participants were found to perform at a level considered to be pathologic; more specifically, 33%, 23%, and 20% failed on Trial Making, Digit Span Backwards, and Frontal Evaluation Battery tests, respectively.


Assuntos
COVID-19 , Idoso , COVID-19/complicações , Humanos , Testes Neuropsicológicos , Síndrome de COVID-19 Pós-Aguda
17.
J Exp Med ; 201(8): 1257-68, 2005 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-15824085

RESUMO

Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix-supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy.


Assuntos
Adenocarcinoma/imunologia , Arginase/antagonistas & inibidores , Linfócitos T CD8-Positivos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Óxido Nítrico Sintase/antagonistas & inibidores , Neoplasias da Próstata/imunologia , Subpopulações de Linfócitos T/imunologia , Tirosina/análogos & derivados , Adenocarcinoma/sangue , Adenocarcinoma/enzimologia , Animais , Arginina/antagonistas & inibidores , Arginina/metabolismo , Linhagem Celular Tumoral , Humanos , Interferon gama/biossíntese , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/enzimologia , Subpopulações de Linfócitos T/química , Tirosina/biossíntese
18.
Am J Prev Med ; 60(1): 13-19, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33041095

RESUMO

INTRODUCTION: As an emerging infectious disease, the clinical and virologic course of COVID-19 requires better investigation. The aim of this study is to identify the potential risk factors associated with persistent positive nasopharyngeal swab real-time reverse transcription‒polymerase chain reaction tests in a large sample of patients who recovered from COVID-19. METHODS: After the acute phase of SARS-CoV-2 epidemic infection, the Fondazione Policlinico A. Gemelli IRCSS of Rome established a post-acute care service for patients discharged from the hospital and recovered from COVID-19. Between April 21 and May 21, 2020, a total of 137 individuals who officially recovered from COVID-19 were enrolled in this study. All patients were tested for the SARS-CoV-2 virus with nucleic acid RT-PCR tests. Analysis was conducted in June 2020. RESULTS: Of the 131 patients who repeated the nasopharyngeal swab, 22 patients (16.7%) tested positive again. Some symptoms such as fatigue (51%), dyspnea (44%), and coughing (17%) were still present in a significant percentage of the patients, with no difference between patients with a negative test and those who tested positive. The likelihood of testing positive for SARS-CoV-2 infection was significantly higher among participants with persistent sore throat (prevalence ratio=6.50, 95% CI=1.38, 30.6) and symptoms of rhinitis (prevalence ratio=3.72, 95% CI=1.10, 12.5). CONCLUSIONS: This study is the first to provide a given rate of patients (16.7%) who test positive on RT-PCR test for SARS-CoV-2 nucleic acid after recovering from COVID-19. These findings suggest that a significant proportion of patients who have recovered from COVID-19 still could be potential carriers of the virus. In particular, if patients continue to have symptoms related to COVID-19, such as sore throat and rhinitis, it is reasonable to be cautious by avoiding close contact, wearing a face mask, and possibly repeating a nasopharyngeal swab.


Assuntos
COVID-19/diagnóstico , Portador Sadio/epidemiologia , Nasofaringe/virologia , Adulto , Idoso , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Faringite/fisiopatologia , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Rinite/fisiopatologia , SARS-CoV-2/isolamento & purificação
19.
Trans R Soc Trop Med Hyg ; 115(1): 74-77, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32948871

RESUMO

BACKGROUND: In East Asia, face masks are commonly worn to reduce viral spread. In Euope and North America, however, their use has been stigmatised for a long time, although this view has radically changed during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Notwithstanding this, it is still unclear whether face masks worn by COVID-19 carriers may indeed prevent viral transmission and environmental contamination. The objective of this study was to evaluate the effectiveness of surgical face masks in filtering SARS-CoV-2. METHODS: Four male patients with COVID-19 were recruited for the study. Two patients wore a surgical mask for 5 h, while two others did not. The spread of the virus in the environment was evaluated through the approved Allplex 2019-nCoV assay. RESULTS: In the room with the two patients without surgical masks, the swab performed on the headboard and sides of the beds was positive for SARS-CoV-2 contamination. In the other room, where two patients were wearing surgical masks, all of the swabs obtained after 5 h tested negative. CONCLUSIONS: The results of the current study add to the growing body of literature supporting the use of face masks as a measure to contain the spread of SARS-CoV-2 by retaining potentially contagious droplets that can infect other people and/or contaminate surfaces. Based on the current evidence, face masks should therefore be considered a useful and low-cost device in addition to social distancing and hand hygiene during the postlockdown phase.


Assuntos
COVID-19/transmissão , Controle de Doenças Transmissíveis/métodos , Pandemias , SARS-CoV-2/crescimento & desenvolvimento , COVID-19/prevenção & controle , COVID-19/virologia , Higiene das Mãos , Humanos , Masculino , Máscaras , Pessoa de Meia-Idade , Distanciamento Físico , Isolamento Social
20.
J Clin Periodontol ; 37(2): 113-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20041974

RESUMO

AIM: Because of the ageing of populations, disability has become an emergent problem from the clinical, social, and economic perspectives. Nevertheless, the determinants of disability in older subjects are still unclear. We assessed the association between self-assessed masticatory dysfunction (MD) and functional ability in older subjects. MATERIALS AND METHODS: We analysed data of all 350 subjects aged 75+ living in Tuscania (Italy). Functional ability was estimated using the Katz' activities of daily living (ADLs), and the Lawton and Brody instrumental activities of daily living (IADLs) scales. RESULTS: MD was reported by 145 (41%) participants. Disability in the ADLs and IADLs was found in 37 (25%) and 53 (37%) of participants with MD, respectively, but only in 11 (5%) and 30 (15%) of the other participants (p<0.001). MD was associated with disability in the ADLs [odds ratio (OR)=2.40, 95% confidence interval (CI)=1.05-5.51], and IADLs (OR=2.77, 95% CI=1.07-7.16) in logistic regression, after adjusting. The association of MD with disability was stronger among subjects aged 80+. CONCLUSIONS: MD is independently associated with disability in community-dwelling elderly. Further studies are needed to evaluate the impact of early detection and correction of MD on the preservation of functional status in older populations.


Assuntos
Atividades Cotidianas , Assistência Odontológica para Idosos , Avaliação da Deficiência , Avaliação Geriátrica , Mastigação , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Inquéritos de Saúde Bucal , Feminino , Planejamento em Saúde , Humanos , Itália , Masculino , Avaliação das Necessidades , Qualidade de Vida , Valores de Referência , Autoexame
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