1,721,065 research outputs found
Clinical Features Associated with Delirium Motor Subtypes in Older Inpatients: Results of a Multicenter Study.
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Advances in nad-lowering agents for cancer treatment
No full textNicotinamide adenine dinucleotide (NAD) is an essential redox cofactor, but it also acts as a substrate for NAD-consuming enzymes, regulating cellular events such as DNA repair and gene expression. Since such processes are fundamental to support cancer cell survival and proliferation, sustained NAD production is a hallmark of many types of neoplasms. Depleting intratumor NAD levels, mainly through interference with the NAD-biosynthetic machinery, has emerged as a promis-ing anti-cancer strategy. NAD can be generated from tryptophan or nicotinic acid. In addition, the “salvage pathway” of NAD production, which uses nicotinamide, a byproduct of NAD degradation, as a substrate, is also widely active in mammalian cells and appears to be highly exploited by a subset of human cancers. In fact, research has mainly focused on inhibiting the key enzyme of the latter NAD production route, nicotinamide phosphoribosyltransferase (NAMPT), leading to the identification of numerous inhibitors, including FK866 and CHS-828. Unfortunately, the clinical activity of these agents proved limited, suggesting that the approaches for targeting NAD production in tumors need to be refined. In this contribution, we highlight the recent advancements in this field, including an overview of the NAD-lowering compounds that have been reported so far and the related in vitro and in vivo studies. We also describe the key NAD-producing pathways and their regulation in cancer cells. Finally, we summarize the approaches that have been explored to optimize the therapeutic response to NAMPT inhibitors in cancer
Cholinesterase Inhibitors: Cardioprotection in Alzheimer's Disease
No full textAlzheimer's disease is a life shortening disease, and the lack of disease modifying therapy implies a huge impact on life expectancy as well as an outgrowing financial and socioeconomic burden. Cholinesterase inhibitors (ChEIs) represent the first line symptomatic therapy, whose benefit to harm ratio is still a matter of debate. Acetylcholinesterase enzyme is a core interest for pharmacological and toxicological research to unmask the fine balance between therapeutic drug efficacy, tolerability, safety, and detrimental effects up to adverse drug reaction. So far, a body of evidence advocated that an increased vagal tone was associated to an increased risk of gastrointestinal and cardiac side effects (negative chronotropic, arrhytmogenic, hypotensive effects), able to hamper ChEIs effects on cognition, reducing administration feasibility and compliance, especially in older and comorbid patients. Conversely, a growing body of evidence is indicating a protective role of ChEIs on overall cardiovascular mortality in patients with dementia, through a series of in vitro and in vivo investigations. The present review is aimed to report the up to date literature in the controversial field of ChEIs and cardioprotection in dementia, offering a state of the art, which may constitute the conceptual framework to be enlarged in order to build higher evidence. Chronic vagal nerve stimulation acted upon by donepezil might improve long term survival through pharmacological properties apart from cholinesterase inhibition, able to offer cardioprotection, abating the overall cardiovascular risk, and, thus profiling a new line of therapeutic intervention for ChEI drug class
NUOVI COMPLESSI DI Pd(II) DI TIPO PORFIRAZINICO MONO- E PENTAMETALLICI COME FOTOSENSIBILIZZATORI IN SOLUZIONE DI DIMETILFORMAMMIDE PER LA PRODUZIONE DI OSSIGENO DI SINGOLETTO, 1O2.
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Determination of nitric oxide solubility in different solvents via the reaction with phthalocyaninatoiron(II)
No full textMedication management ability in older patients: Time for a reappraisal
No full textBackground. Adhering to drug regimens is a complex and multidimensional task. Elderly patients usually take an average of seven drugs but most fail to adhere to the prescribed regimen. Several performance-based instruments have been developed to assess a patient’s capacity to manage drugs but with inconsistent results. Aims. The aim of the study was to assess the prevalence of impaired medical management capacity in a sample of the oldest old hospitalized elderly patients and the main clinical factors associated with potential unintentional non-adherence. Methods. Forty-six consecutive patients were enrolled in the geriatric transitional care unit of Ospedale Policlinico San Martino, Genoa, Italy. All patients received an abbreviated comprehensive geriatric assessment and a hand grip assessment for sarcopenia. Patients’ medication management ability was assessed by administering the DRUGS tool 48-74 hours before hospital discharge. Results. The results showed a negative correlation between age and total medication management score. A positive correlation was detected between functional status, cognitive status, and medication management score. Hand grip strength < 9 kg correlated with a significant worsening of medical management capacity. In contrast, multiple morbidities and the mean number of drugs were not associated with the medical management score. Conclusions. This preliminary study indicated that drug management capacity mainly relies on frailty markers, such as functional status, sarcopenia, and cognitive performance. Further studies are warranted to identify a subset of medical parameters that can accurately predict impaired medical management ability early, particularly for highly vulnerable elderly patients
EQUILIBRIUM AND KINETIC-STUDY OF IMIDAZOLE BINDING TO PHTHALOCYANINATOIRON(II) IN DIMETHYL-SULFOXIDE
No full textBehavioral disturbances in dementia and beyond: Time for a new conceptual frame?
No full textAlzheimer’s disease and vascular dementia are estimated to be the most common causes of dementia, although mixed dementia could represent the most prevalent form of dementia in older adults aged more than 80 years. Behavioral disturbances are common in the natural history of dementia. However, so far, there is a paucity of studies that investigated the causal association between behavioral psychological symptoms of dementia and dementia sub-types, due to the high heterogeneity of methodology, study design and type of clinical assessment. To understand the scant evidence on such a relevant clinical issue, it could be hypothesized that a new shifting paradigm could result in a better identification of the relationship between behavioral disturbances and dementia. This narrative review provides an update of evidence on the behavioral patterns associated with different dementia sub-types and offers a potential future perspective as common ground for the development of new translational studies in the field of behavioral disturbances in dementia and the appropriateness of psychoactive treatments
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