Sintesi e caratterizzazione di cluster Ag-Cu-Fe, Au-Cu-Fe e Ni-Pd

Durante il mio periodo di tirocinio mi sono occupato della sintesi e caratterizzazione di cluster carbonilici eterometallici, ed in particolare di cluster Ag-Cu-Fe, Au-Cu-Fe, e Ni-Pd. In un primo momento il lavoro si è concentrato sullo studio della reazione tra cluster Cu-Fe e sali di Ag e Au, con lo scopo di ottenere specie Ag-Cu-Fe, e Au-Cu-Fe. Nella seconda parte l’attività è stata incentrata sulla sintesi di cluster Ni-Pd ad elevata nuclearità, attraverso reazioni tra [Ni6(CO)12]2- e composti di Pd(II). In entrambi i casi le sintesi sono state condotte variando i rapporti stechiometrici dei reagenti e i solventi, permettendo l’ottenimento di specie, caratterizzate spettroscopicamente mediante tecnica IR. In alcuni casi è stato anche possibile ottenere cristalli caratterizzati strutturalmente tramite diffrattometria a raggi X. Le reazioni di [Cu3Fe3(CO)12]3- con quantità crescenti di M=Ag, Au danno luogo alla formazione in sequenza di [Cu5Fe4(CO)16]3-, [MxCu5-xFe4(CO)16]3- (x = 0-5), [M5Fe4(CO)16]3-, [M6Fe4(CO)16]2-. Successivamente, nel caso in cui M= Ag, un ulteriore aggiunta di sali di M+ porta alla formazione di [Ag13Fe8(CO)32]3-, mentre se M= Au si formano i cosiddetti “bruni d’oro” e alla fine, [AuFe4(CO)16]-. Le specie [MxCu5-xFe4(CO)16]3- risultano particolarmente interessanti dato che possono essere viste come leghe molecolari M/Cu, che mostrano disordine sia sostituzionale che composizionale. Per quanto riguarda i cluster Ni-Pd sono state ottenute tre nuove specie carboniliche ad elevata nuclearità, ovvero [Ni37-xPd7+x(CO)48]6- (x= 0,69), [HNi37-xPd7+x(CO)48]5- (x= 0,53) and [Ni22-xPd20+x(CO)48]6- (x = 0.63). In tutte queste strutture il Pd tende ad occupare posizioni che minimizzano le interazioni Pd-CO massimizzando le interazioni M-M, mentre l’opposto risulta per il Ni. Ciò si traduce in una parziale segregazione dei due metalli, anche se alcuni fenomeni di disordine (sostituzionale e composizionale) sono presenti in tali strutture.

Chemo-physical and biological mechanisms behind the anticancer activity of plasma activated Ringer's Lactate solution for the treatment of peritoneal carcinosis from primitive epithelial ovarian/tubular tumor

Cancer research and development of targeting agents in this field is based on robust studies using preclinical models. The failure rate of standardized treatment approaches for several solid tumors has led to the urgent need to fine-tune more sophisticated and faithful preclinical models able to recapitulate the features of in vivo human tumors, with the final aim to shed light on new potential therapeutic targets. Epithelial Ovarian Cancer (EOC) serous histotype (HGSOC) is one of the most lethal diseases in women due to its high aggressiveness (75% of patients diagnosed at FIGO III-IV state) and poor prognosis (less of 50% in 5 years), whose therapy often fails as chemoresistance sets in. This thesis aimed at using the novel perfusion-based bioreactor U-CUP that provides direct perfusion throughout the tumor tissue seeking to obtain an EOC 3D ex vivo model able to recapitulate the features of the original tumor including the tumor microenvironment and maintaining its cellular heterogeneity. Moreover, we optimized this approach so that it can be successfully applied to slow-frozen tumoral tissues, further extending the usefulness of this tool. We also investigated the effectiveness of Plasma Activated Ringer’s Lactate solution (PA-RL) against Epithelial Ovarian Cancer (EOC) serous histotype in both 2D and 3D cultures using ex-vivo specimens from HGSOC patients. We propose PA-RL as a novel therapy with local intraperitoneal administration, which could act on primary or metastatic ovarian tumors inducing a specific cancer cell death with reduced damage on the surrounding healthy tissues.

Carbapenemase producing enterobacteriacae rectal colonization in dialysis patients: a large monocentric retrospective analysis

Carbapenemase-producing Enterobacteriaceae (CPE) represent a growing global public health concern due to their increasing prevalence and resistance to carbapenems, a group of last-resort antibiotics. Dialysis patients, who often have compromised immune systems, are particularly vulnerable to infections that represent the second cause of death in dialysis’ cohorts. Presenting a rectal colonization by CPE has a significative impact on patients in dialysis? Are there factors that can help us understand which patients are at a higher risk of developing CPE colonization? How can we treat a CPE colonized patient who develop fever? Our study aim to reviews the challenges posed by CPE in dialysis settings and explores current diagnostic, therapeutic, and infection control strategies on a large cohort of dialyzed patients.

Characterizing “Exposure-PK/PD-Biomarker” relationships in patients with hematologic malignancies

Antimicrobial stewardship programs are gaining more and more relevance in optimizing anti-infective treatment and in preventing the emergence of antimicrobial resistance. Personalization of antimicrobial treatment based on real-time therapeutic drug morning (TDM) and dosing adaptation may represent an important tool in antimicrobial stewardship programs. In this Ph.D project, we aim to focus on differences in pharmacokinetics (PK) for meropenem and piperacillin/tazobactam and host response biomarkers (e.g., C-reactive protein) in severe Gram‐negative related infections occurring in oncohematologic patients. We are interested in identifying optimized model‐based individualized dosing strategies for these antibiotics focusing on biomarkers-guided prediction of PK and pharmacodynamic (PD) parameters using population PK/PD modelling. We expect to identify optimal model‐based dosing targets for these antibiotics for special populations for implementation in TDM routines, and mathematical models characterizing the relationship between biomarkers and outcomes in these populations.

Modalidades de terapia renal substitutiva: hemodiálise e diálise peritoneal

Texto que compõe a unidade 3 do módulo “Manejo clínico das doenças renais” do Curso de Especialização em Nefrologia Multidisciplinar, produzido pela UNA-SUS/UFMA. Aborda as duas modalidades de terapia de substituição renal: a hemodiálise e a diálise peritoneal. Apresenta também as vantagens e desvantagens de cada terapia e a importância de orientar de maneira clara sobre as opções de escolha para que o paciente e sua família se sintam confortáveis.

Diálise peritoneal

Este material compõe o Curso de Especialização em Nefrologia Multidisciplinar (Unidade 3, Módulo 6), produzido pela UNA-SUS/UFMA. Trata-se de um vídeo que apresenta como a solução de diálise consegue depurar as toxinas e quais são os benefícios e limitações desta terapia.

Diálise peritoneal ambulatorial contínua

Este material compõe o Curso de Especialização em Nefrologia Multidisciplinar (Unidade 3, Módulo 6), produzido pela UNA-SUS/UFMA. Trata-se de um recurso educacional interativo que apresenta o processo de troca da solução de diálise, durante a DPAC (Diálise peritoneal ambulatorial contínua), também chamada de troca manual.

Diálise peritoneal: saída do líquido acumulado

Este material compõe o Curso de Especialização em Nefrologia Multidisciplinar (Unidade 3, Módulo 6), produzido pela UNA-SUS/UFMA. Trata-se de um recurso educacional interativo que apresenta o processo de osmose, ultrafiltração, difusão, convecção e permanência do líquido acumulado no organismo do paciente durante a diálise peritoneal.

Ingestão de cálcio, fósforo e vitamina D por indivíduos em diálise peritoneal

Este material compõe o Curso de Especialização em Nefrologia Multidisciplinar (Módulo 7, Unidade 4), produzido pela UNA-SUS/UFMA. Trata-se de um recurso educacional interativo que apresenta recomendações sobre a ingestão de fósforo, cálcio e vitamina D, por pacientes em diálise peritoneal.

Modalidades de terapia renal substitutiva: hemodiálise e diálise peritoneal

Neste vídeo, o Dr. Roberto Flávio Pecoits Filho explica as características de cada modalidade do tratamento dialítico, a diálise peritoneal e hemodiálise. A primeira é realizada na casa do paciente, necessitando de treinamento para os familiares, uma adequada comunicação à distância com a equipe médica e armazenamento correto do material. Já a hemodiálise é realizada em uma clínica com equipamento e equipe especializada. Ambas necessitam de atenção redobrada às complicações, que podem culminar em problemas cardiovasculares.

Adapting The Sniffin' Sticks Olfactory Test To Diagnose Parkinson's Disease In Estonia.

The aim of the study was to develop a culturally adapted translation of the 12-item smell identification test from Sniffin' Sticks (SS-12) for the Estonian population in order to help diagnose Parkinson's disease (PD). A standard translation of the SS-12 was created and 150 healthy Estonians were questioned about the smells used as response options in the test. Unfamiliar smells were replaced by culturally familiar options. The adapted SS-12 was applied to 70 controls in all age groups, and thereafter to 50 PD patients and 50 age- and sex-matched controls. 14 response options from 48 used in the SS-12 were replaced with familiar smells in an adapted version, in which the mean rate of correct response was 87% (range 73-99) compared to 83% with the literal translation (range 50-98). In PD patients, the average adapted SS-12 score (5.4/12) was significantly lower than in controls (average score 8.9/12), p < 0.0001. A multiple linear regression using the score in the SS-12 as the outcome measure showed that diagnosis and age independently influenced the result of the SS-12. A logistic regression using the SS-12 and age as covariates showed that the SS-12 (but not age) correctly classified 79.0% of subjects into the PD and control category, using a cut-off of <7 gave a sensitivity of 76% and specificity of 86% for the diagnosis of PD. The developed SS-12 cultural adaption is appropriate for testing olfaction in Estonia for the purpose of PD diagnosis.

Is Thyroid Stunning Clinically Relevant? A Retrospective Analysis Of 208 Patients.

Current guidelines have advised against the performance of (131)I-iodide diagnostic whole body scintigraphy (dxWBS) to minimize the occurrence of stunning, and to guarantee the efficiency of radioiodine therapy (RIT). The aim of the study was to evaluate the impact of stunning on the efficacy of RIT and disease outcome. This retrospective analysis included 208 patients with differentiated thyroid cancer managed according to a same protocol and followed up for 12-159 months (mean 30 ± 69 months). Patients received RIT in doses ranging from 3,700 to 11,100 MBq (100 mCi to 300 mCi). Post-RIT-whole body scintigraphy images were performed 10 days after RIT in all patients. In addition, images were also performed 24-48 hours after therapy in 22 patients. Outcome was classified as no evidence of disease (NED), stable disease (SD) and progressive disease (PD). Thyroid stunning occurred in 40 patients (19.2%), including 26 patients with NED and 14 patients with SD. A multivariate analysis showed no association between disease outcome and the occurrence of stunning (p = 0.3476). The efficacy of RIT and disease outcome do not seem to be related to thyroid stunning.

Feasibility And Reproducibility Of Diffusion-weighted Magnetic Resonance Imaging Of The Fetal Brain In Twin-twin Transfusion Syndrome.

The aim of this study is to test the feasibility and reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) evaluations of the fetal brains in cases of twin-twin transfusion syndrome (TTTS). From May 2011 to June 2012, 24 patients with severe TTTS underwent MRI scans for evaluation of the fetal brains. Datasets were analyzed offline on axial DW images and apparent diffusion coefficient (ADC) maps by two radiologists. The subjective evaluation was described as the absence or presence of water diffusion restriction. The objective evaluation was performed by the placement of 20-mm(2) circular regions of interest on the DW image and ADC maps. Subjective interobserver agreement was assessed by the kappa correlation coefficient. Objective intraobserver and interobserver agreements were assessed by proportionate Bland-Altman tests. Seventy-four DW-MRI scans were performed. Sixty of them (81.1%) were considered to be of good quality. Agreement between the radiologists was 100% for the absence or presence of diffusion restriction of water. For both intraobserver and interobserver agreement of ADC measurements, proportionate Bland-Altman tests showed average percentage differences of less than 1.5% and 95% CI of less than 18% for all sites evaluated. Our data demonstrate that DW-MRI evaluation of the fetal brain in TTTS is feasible and reproducible.

Elevated Micronucleus Frequency In Patients With Type 2 Diabetes, Dyslipidemia And Periodontitis.

The over-production of reactive oxygen species (ROS) can cause oxidative damage to a large number of molecules, including DNA, and has been associated with the pathogenesis of several disorders, such as diabetes mellitus (DM), dyslipidemia and periodontitis (PD). We hypothesise that the presence of these diseases could proportionally increase the DNA damage. The aim of this study was to assess the micronucleus frequency (MNF), as a biomarker for DNA damage, in individuals with type 2 DM, dyslipidemia and PD. One hundred and fifty patients were divided into five groups based upon diabetic, dyslipidemic and periodontal status (Group 1 - poor controlled DM with dyslipidemia and PD; Group 2 - well-controlled DM with dyslipidemia and PD; Group 3 - without DM with dyslipidemia and PD; Group 4 - without DM, without dyslipidemia and with PD; and Group 5 - without DM, dyslipidemia and PD). Blood analyses were carried out for fasting plasma glucose, HbA1c and lipid profile. Periodontal examinations were performed, and venous blood was collected and processed for micronucleus (MN) assay. The frequency of micronuclei was evaluated by cell culture cytokinesis-block MN assay. The general characteristics of each group were described by the mean and standard deviation and the data were submitted to the Mann-Whitney, Kruskal-Wallis, Multiple Logistic Regression and Spearman tests. The Groups 1, 2 and 3 were similarly dyslipidemic presenting increased levels of total cholesterol, low density lipoprotein cholesterol and triglycerides. Periodontal tissue destruction and local inflammation were significantly more severe in diabetics, particularly in Group 1. Frequency of bi-nucleated cells with MN and MNF, as well as nucleoplasmic bridges, were significantly higher for poor controlled diabetics with dyslipidemia and PD in comparison with those systemically healthy, even after adjusting for age, and considering Bonferroni's correction. Elevated frequency of micronuclei was found in patients affected by type 2 diabetes, dyslipidemia and PD. This result suggests that these three pathologies occurring simultaneously promote an additional role to produce DNA impairment. In addition, the micronuclei assay was useful as a biomarker for DNA damage in individuals with chronic degenerative diseases.