Intended pharmacotherapeutical approaches of Alzheimer's disease therapy

Alzheimer's disease is a progressive neurodegenerative disorder mainly manifested by memory loss, personality changes, and cognitive dysfunction. Despite the fact that tireless research is being conducted, up-to-date pharmacotherapy of AD is presented only by two groups diverging in the mechanism of action. The larger one uses acetylcholinesterase inhibitors, and the second group is represented by the N-methyl-D-aspartate antagonist memantine. Even though the etiology of Alzheimer's disease is unknown, several different therapeutic approaches are being investigated. The aim of this paper is to provide an overview of the present state of intended therapeutics for AD, describing their mechanism of action if known, displaying chemical structures, and the state of clinical trials if any.     

Monocytes link atherosclerosis and cancer

From many perspectives, cardiovascular diseases and cancers are fundamentally different. On the one hand, atherosclerosis is a disease of lipid accumulation driven by diet and lifestyle, whereas cancer is an attack "from within" driven by mutations. Nevertheless, studies over the past 20 years have forced us to re-evaluate such a view. We are learning that, among other factors, the immune system is indispensable for the development and progression of both diseases. Its components are not only reactive but can also orchestrate both tumor and atherosclerotic lesion growth. In this Viewpoint, we explore how monocytes, which are key constituents of the immune system, forge links between cardiovascular diseases and cancers.     

The selective growth inhibition of oral cancer by iron core-gold shell nanoparticles through mitochondria-mediated autophagy

Nanoparticles with an iron core and gold shell (denoted "Fe@Auó") have been reported to limit cancer-cell proliferation and therefore have been proposed as a potential anti-cancer agent. However, the underlying mechanisms are still unknown. In this study, we used flow cytometry, confocal fluorescence microscopy, and transmission electron microscopy to analyse the morphological and functional alterations of mitochondria in cancerous cells and healthy cells when treated with Fe@Au. It was found that Fe@Au caused an irreversible membrane-potential loss in the mitochondria of cancer cells, but only a transitory decrease in membrane potential in healthy control cells. Production of reactive oxygen species (ROS) was observed; however, additions of common ROS scavengers were unable to protect cancerous cells from the Fe@Au-induced cytotoxicity. Furthermore, iron elements, before oxidation, triggered mitochondria-mediated autophagy was shown to be the key factor responsible for the differential cytotoxicity observed between cancerous and healthy cells.     

Clinicopathological features of ovarian Brenner tumors in Montenegro

Aim

The aim of this study was to describe the clinicopathological characteristics of ovarian Brenner tumors in Montenegro.

Methods

Twelve female patients (aged 53–80 years; mean 65 years) with ovarian Brenner tumors were selected from our histopathology records between 2010 to 2012.

Results

Tumor size ranged between 1 and 13 cm (mean 8 cm): of these, ten were benign (83%) and two were malignant (27%). Eight tumors (67%) were found incidentally. One patient (8%) had bilateral Brenner tumors. Nine patients (75%) had coexisting tumors: five (42%) coexisting mucinous cystadenomas, one (8%) mucinous cystadenocarcinoma, two (17%) endometrial carcinomas of the endometrium, and one (8%) endometrial polyp.

Conclusions

Brenner tumors are most frequently solid neoplasms of the ovary, found by chance, and may be associated with other ovarian or uterine epithelial neoplasms.     

‘We’re stuck in the corner’: Young women,embodiment and drinking in the countryside

The methodologies of school and household surveys for monitoring substance use among adolescents are compared, their respective strengths and weaknesses described and directions for improvement indicated. This work is in part based on our experience with the ongoing Dutch National School Survey, which is a monitor on substance use and its putative risk factors. It is held every 4 years among samples of 10 000 students. Starting in 1984 we now have five waves of data. Our experiences are placed in the broader context of the literature and several conclusions are drawn. The school survey offers a number of benefits: participation rates are high, costs per respondent are low, and substance use among minority groups can be monitored well. The school survey generates relevant contextual information on fellow-students, classes and schools. It can also generate contextual information on the students' households and the communities in which they live. Further, aetiological inference is enhanced when the school survey is designed as a cohort study. This, however, is only a viable option when data collecting is carried out at least every 2 years and depends on information needs.     

Polydrug Use Among Secondary School Students: combinations,prevalences and risk profiles

The aim is to describe polydrug use among secondary school students: combinations of substances, number of students per user type and corresponding risk profiles. The method employed was as follows. Data were derived from the 1999 sample of the Dutch National School Survey on Substance Use. The analysis was limited to secondary school students between 12 and 16 years, at which age it is still compulsory to attend school (N = 6236). Studied substances are alcohol, tobacco, cannabis, ecstasy, amphetamines, opiates and cocaine. Of the students, 56.7% used one or more substances. Among the users, 41.8% were polydrug users in the sense that they had used more than one substance during the previous 4 weeks. In the student population concerned of about 1 000 000, 243 000 were polydrug users of whom 146 000 use only alcohol and tobacco, 67 000 combine alcohol or tobacco with cannabis, and 21 000 combine alcohol, tobacco or cannabis with at least one hard drug such as ecstasy, cocaine, amphetamines or heroin. The risk of polydrug use increased with increasing age. Prevalence rates were highest among ethnic Dutch students, very low among Moroccan students and high at the lower educational levels. By comparison with girls, boys had a specific risk of becoming the type of polydrug user using soft or hard drugs. The high prevalence of polydrug use among young students makes this an important topic for research, monitoring and prevention.     

Barriers to Study Enrollment in Patients With Advanced Cancer Referred to a Phase I Clinical Trials Unit

Background.

We conducted this retrospective study to identify reasons that patients referred to a phase I clinical trial failed to enroll or delayed enrollment onto the trial.

Materials and Methods.

Outcome analyses were conducted independently on data collected from electronic medical records of two sets of consecutive patients referred to a phase I clinical trial facility at MD Anderson Cancer Center. Data from the first set of 300 patients were used to determine relevant variables affecting enrollment; data from the second set of 957 patients were then analyzed for these variables.

Results.

Results from the two sets of patients were similar. Approximately 55% of patients were enrolled in a phase I trial. Patients referred from within MD Anderson were more likely to be enrolled than patients seen originally outside the institution (p = .006); black patients were more likely than white patients to enroll (69% vs. 43%; p = .04). The median interval from the initial visit to initiation of treatments was 19 days. Major reasons for failure to enroll included failure to return to the clinic (36%), opting for treatment in another clinic (17%), hospice referral (11%), early death (10%), and lack of financial clearance (5%). Treatment was delayed for three weeks or more in 250 patients; in 85 patients (34%), the delay was caused by financial and insurance issues.

Conclusion.

Failure to return to the clinic, pursuit of other therapy, and rapid deterioration were the major reasons for failure to enroll; lengthy financial clearance was the most common reason for delayed enrollment onto a phase I trial.     

Thermal, dynamic mechanical, and dielectric analyses of some polyurethane biocomposites

Polymer biocomposites based on segmented poly(ester urethane) and extracellular matrix components have been prepared for the development of tissue engineering applications with improved biological characteristics of the materials in contact with blood and tissues for long periods. Thermal, dynamical, and dielectrical analyses were employed to study the molecular dynamics of these materials and the influence of changing the physical network morphology and hydrogen bond interactions accompanied by phase transitions, interfacial effects, and polarization or conductivity. All phenomena that concur in the tested materials are evaluated by cross-examination of the dynamic mechanical characteristic properties (storage modulus, loss modulus, and loss factor) and dielectric properties (relative permittivity, relative loss factor, and loss tangent) as a function of temperature. Comparative aspects were elucidated by calculating the apparent activation energies of multiplex experiments.