Platinum-based anticancer chemotherapy is associated to severe side effects because of its poor specificity. In particular, the hydrolysis of Pt-based drugs generates cationic complexes with ...electrophylic properties able to target DNA. The effectiveness of this kind of chemotherapy relies solely on the proliferation index of tumour cells, which is higher than in healthy cells. In recent years, the "drug targeting and delivery" approach has been developed in an attempt to reduce chemotherapy-related systemic side effects by using vectors that selectively deliver the cytotoxic agent to tumour cells, thus sparing healthy cells. These vectors include bioactive substances, such as nutrients, that more readily enter metabolically active tumour cells, or hormones, folates and bile acids, that are selectively conveyed by receptors/transporters often over-expressed in cancer cells (active targeting). Alternatively, macromolecular vectors, exploiting the so-called EPR (enhanced permeability and retention) effect, can be used (passive targeting). The bioactive or macromolecular vector must contain a coordinating arm capable of binding the PtX(2)-unit, acting either as carrier or leaving group for the cytotoxic Pt-moiety. In both cases, the Pt-vector conjugate should be promptly cleaved to generate the active species. The release of platinum drugs from the pharmacophore is crucial for fine-tuning of the overall cytotoxic properties of the conjugates. The "drug targeting and delivery" method represents an exciting field of research for improving the therapeutic potential of the long established, very efficient, but intrinsically non-specific Pt-based drugs.
The cisplatin-sensitive human ovarian cancer cells A2780 have been challenged with cationic liposomes containing the single drug cisplatin or valproate or their combination with an approximate 1 : 2 ...molar ratio, i.e. the same ratio present in preformed (OC-6-33)-diamminedichloridobis(valproato)platinum(iv), that releases such metabolites by intracellular Pt(iv) → Pt(ii) reduction. The results of this comparison confirm that valproate barely penetrates cells unless it is transported by liposomes or it is coordinated to a lipophilic Pt(iv) assembly. The two drugs have a synergistic action, cisplatin being the more potent antiproliferative agent. Even if the preformed (OC-6-33)-diamminedichloridobis(valproato)platinum(iv) releases cisplatin and valproate in the same amount as the liposome formulation, the Pt(iv) derivative is more active. This important feature, common to all Pt(iv) complexes having very lipophilic carboxylates, is attributable to their propensity to remain in cells and to continuously bind DNA, unlike cisplatin that is partially removed from cells by efficient efflux pathways.
Nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups were proposed as potential delivery systems for Pt(iv) antitumor prodrugs. Spherical SNPs containing two ...different external arms, i.e. 3-aminopropyl and N-(6-aminohexyl)aminomethylene, of around 125 nm hydrodynamic diameter were loaded with two different cisplatin-based Pt(iv) complexes, namely (OC-6-44)-diamminedichloridoethoxidosuccinatoplatinum(iv) and (OC-6-44)-diamminedichloridoacetylamidosuccinatoplatinum(iv), through the formation of amide bonds between the pendant amino groups on SNPs and the free carboxylic group of the complexes. In the presence of the N-(6-aminohexyl)aminomethylene arm, the Pt(iv)-SNP conjugates showed a negligible (unwanted) Pt release by hydrolysis, whereas in the presence of ascorbic acid the reduction of Pt(iv) → Pt(ii) caused the substantial release of the active metabolite cisplatin. Conjugate Pt(iv)-SNP exhibited better antiproliferative activity on the Pt-sensitive A2780 human ovarian cancer cell line than the parent cisplatin and their free Pt(iv) precursors, due to their more efficient cellular uptake, likely by endocytosis.
Intensity-modulated radiation therapy (IMRT) for nasopharyngeal cancer (NPC) allowed a better distribution of the dose to the tumor volume, sparing surrounding structures. Aim of the study is the ...objective evaluation of olfactory and gustatory impairments in patients who underwent chemo-radiotherapy for NPC. Correlation between smell and taste alterations, xerostomy, and radiation technique was investigated. Thirty healthy subjects and 30 patients treated with chemo-radiation therapy for NPC, with at least a 2-years follow-up period, were evaluated. All subjects underwent symptoms evaluation, endoscopic fiber optic nasal examination, taste strips, Sniffin' sticks tests, Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring system. Patients were divided in 2 groups: 2-dimensional radiotherapy/conformal 3-dimensional radiotherapy and IMRT. A higher percentage of rhinorrhea, nasal obstruction, xerostomy, hyposmia, hypogeusia, mucosal hyperemia, and presence of nasopharyngeal secretions was found in irradiated subjects (P < 0.05). Concerning olfactory and gustatory scores, we demonstrated a statistically significant difference between healthy subjects and irradiated patients (P < 0.05), with lower gustatory total score in IMRT group (P < 0.01). In conclusion, chemo-radiotherapy for NPC induces long-term smell and taste impairments, which can compromise quality of life. Although based on small samples, it is also important to consider that IMRT can induce higher taste dysfunction compared with traditional techniques.
Background. Chronic kidney disease (CKD) is associated with poor renal and cardiovascular (CV) outcome, and early identification largely depends on the general practitioners’ (GPs) awareness of it. ...Only a few studies have evaluated the prevalence of CKD in type 2 diabetes in primary care, and no studies are available on hypertensive diabetics. Thus, the aim of this study was to assess the prevalence of CKD and its association with CV morbidity in such a population. Methods. On the basis of an Italian national project involving GPs and nephrologists, we retrieved demographic, laboratory and clinical data regarding 7582 hypertensive type 2 diabetics (3564 men; age 25–89 years) who were selected using the diagnostic code Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for diabetes and hypertension. Blood pressure (BP) values, serum creatinine, ECG-diagnosed left ventricular hypertrophy (LVH) and the occurrence of previous major CV events were obtained for each patient from the GPs’ Health Search Database. Estimated glomerular filtration rate (GFR) was calculated according to the four-variable MDRD equation. CKD was defined as an estimated GFR < 60 mL/min/ 1.73 m2. Results. CKD prevalence was 26%, although renal disease was diagnosed by GPs in only 5.4% of cases. The prevalence of both LVH and major CV events was 8%. Adequate BP control was only achieved in 10.4% of patients. Patients whose GFR was <60 mL/min/1.73 m2 were older, prevalently female, had increased pulse pressure and higher prevalence of dyslipidaemia. Moreover, the prevalence of both LVH and major CV events was higher in patients with CKD as compared to patients with normal GFR. Multivariate logistic regression analysis showed that patients with CKD had a higher risk of LVH and/or CV events adjusted for eight covariates, and this risk increased by 23% with each 21 mL/min/1.73 m2 decrease in GFR. Conclusions. This study shows that CKD is highly prevalent in hypertensive type 2 diabetic patients, where it is a strong predictor of CV adverse outcome. However, awareness of CKD by GPs is low. Equations for calculating estimated GFR should be included in the GPs’ database in order to detect the presence of CKD and to improve CV outcome of such a high-risk population.
Introduction
Despite the availability of sophisticated devices and suitable recommendations on how to best perform insulin injections, lipohypertrophy (LH) and bruising (BR) frequently occur as a ...consequence of improper injection technique.
Aim
The purpose of this nationwide survey was to check literature-reported LH risk factors or consequences for any association with BR
Method
This was a cross-sectional, observational, multicenter study based on the identification of skin lesions at all patient-reported insulin injection sites in 790 subjects with diabetes. General and injection habit-related elements were investigated as possible BR risk factors.
Results
While confirming the close relationship existing between LH and a full series of factors including missed injection site rotation, needle reuse, long-standing insulin treatment, frequent hypoglycemic events (hypos), and great glycemic variability (GV), the observed data could find no such association with BR, which anyhow came with high HbA1c levels, missed injection site rotation, and long-standing insulin treatment.
Conclusion
BR most likely depends on the patient’s habit of pressing the injection pen hard onto the skin. Despite being worrisome and affecting quality of life, BR seems to represent a preliminary stage of LH but does not affect the rate of hypos and GV.
Trial Registration
207/19.09.2017
Results of the Italian neu_ART project Re, A; Albertin, F; Bortolin, C ...
IOP conference series. Materials Science and Engineering,
01/2012, Letnik:
37, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The neu_ART project aims at developing state of the art transmission imaging and computed tomography techniques, applied to art objects, by using neutrons as well as more conventional X-rays. In this ...paper a facility for digital X-ray radiography of large area paintings on canvas or wooden panels and for the X-ray tomography of large size wooden artifacts, recently installed in a protected area, is presented. The results of a K-edge radiography facility that will soon be installed in the same area are also shown.
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