Neuroimaging diagnosis in neurodegenerative diseases

Dementia affects about 8% of people age 65 years and older. Identification of dementia is particularly difficult in its early phases when family members and physicians often incorrectly attribute the patient’s symptoms to normal aging. The most frequently occurring ailments that are connected with neurodegeneration are: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. A variety of powerful techniques that have allowed visualization of organ structure and function with exact detail have been introduced in the last twenty-five years. One such neuroimaging technique is positron emission tomography (PET), which measures in detail the functioning of distinct areas of the human brain and as a result plays a critical role in clinical and research applications. Radiotracer-based functional imaging provides a sensitive means of recognizing and characterizing the regional changes in brain metabolism and receptor binding associated with cognitive disorders. The next functional imaging technique widely used in the diagnosis of cognitive disorders is single photon emission computed tomography (SPECT). New radiotracers are being developed and promise to expand further the list of indications for PET. Prospects for developing new tracers for imaging other organ diseases also appear to be very promising. In this review, we present current opportunities of neuroimaging techniques in the diagnosis and differentiation of neurodegenerative disorders. Nuclear Med Rev 2010; 13, 1: 23–3

The role of vitamin C in skin care and health

Background. The effect of vitamin C on the skin. The skin is a protective barrier against harmful factors from the external environment, which is due to its unique structure. The skin contains vitamin C in various concentrations depending on the individual layers. Skin keratinocytes have the capacity to accumulate high concentrations of vitamin C, which may reduce inflammation caused by excessive exposure to UV irradiation. Aim of the study. The aim of the study was to systematize knowledge about the topical use of vitamin C in the care or treatment of skin defects based on a literature review and to indicate potential benefits in damages related to the overproduction of reactive oxygen species (ROS) and the skin aging process. Materials and methods. The literature review was performed by searching scientific databases: PubMed and Google Scholar. The search for relevant articles on the role of vitamin C in the skin was carried out using the following keywords: “vitamin C", "ascorbic acid", "magnesium ascorbyl phosphate", "ascorbyl-6-palmitate", "skin", "photoprotection", "photoaging". In order to increase the efficiency of work, the authors developed a concept of the publication that included division into subchapters that were assigned to individual authors in order to avoid duplicating information while editing the manuscript. The described methodology allowed for obtaining reliable information. Results. Vitamin C protects the keratinocyte from apoptosis and increases cell survival. It acts as an antioxidant that plays an important role by stimulating collagen synthesis and assisting in antioxidant protection against UV-induced photodamage. Vitamin C also influences gene expression of antioxidant enzymes, the organisation and accumulation of phospholipids, and promotes the formation of the stratum corneum and the differentiation of the epithelial cells in general. The provision of vitamin C to the skin greatly assists wound healing and minimises raised scar formation. Vitamin C supplementation for nutritional purposes is also important and can be combined with topical application. The effect of the comprehensive action of vitamin C is to protect tissues against oxidative damage by removing free radicals that damage the most important structures of the body: cell membranes, DNA and proteins. Conclusions. The effectiveness of vitamin C affects the condition of the skin and the rate of its aging. This study contains examples of research methods for reconstructed human epidermis or keratinocytes, but the literature review shows that these models lack other skin components such as fibroblasts, Langerhans cells, melanocytes and hair follicles. The human skin model has been developed in laboratories and is currently limited by the lack of many critical biological and structural features of the skin. Engineering a human skin equipped with, among others, into immune cells and capable of generating all components, including appendages, is a major challenge. Therefore, further research is needed to elucidate the exact mechanisms of action of vitamin C using a human skin model that containing other skin components

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer’s disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future

<Book Review> Yamanoi Kazunori, How does the politics change the social security

WSTĘP. Celem pracy była ocena wpływu otyłości oraz cukrzycy typu 2 na przerost lewej komory serca u pacjentów z nadciśnieniem tętniczym. MATERIAŁ I METODY. Badaniem objęto grupę 554 osób z nadciśnieniem tętniczym (62% mężczyzn, 38% kobiet) oraz 97 osób z nadciśnieniem tętniczym i cukrzycą typu 2 (61% mężczyzn, 39% kobiet). Średni wiek w obu grupach wynosił 53 &#177; 13 lat v. 58 &#177; 8 lat. U wszystkich badanych wykonano echokardiografię, dwukrotny pomiar ciśnienia tętniczego, mierzono obwód talii i bioder oraz określano wskaźnik masy ciała (BMI). WYNIKI. Masa lewej komory (LVM) oraz wskaźnik masy lewej komory serca (LVMI) były istotnie wyższe w grupie osób z nadciśnieniem tętniczym i cukrzycą typu 2 w porównaniu z grupą osób bez cukrzycy, wynosiły one odpowiednio: LVM &#8212; 280,6 &#177; 67,4 g v. 247,3 &#177; 74,8 g, p < 0,0001; LVMI &#8212; 145,2 &#177; 33 g/ /m2 v. 129,9 &#177; 36 g/m2, p < 0,0001. W przypadku osób z nadciśnieniem tętniczym nieobciążonych cukrzycą wykazano dodatnią korelację BMI z LVMI (r = 0,17, p < 0,0001), zarówno wśród mężczyzn, jak i kobiet. W przypadku wskaźnika talia/biodro wykazano dodatnią korelację z LVMI tylko w grupie kobiet (r = 0,26, p < 0,0001). U pacjentów ze współistniejącą cukrzycą typu 2 nie stwierdzono związku BMI oraz wskaźnika talia/biodro z przerostem lewej komory serca. WNIOSKI. Czynnikami zwiększającymi ryzyko przerostu lewej komory serca wśród osób z nadciśnieniem tętniczym są wysoki wskaźnik masy ciała oraz otyłość brzuszna w przypadku kobiet. Pacjenci ze współistniejącą cukrzycą typu 2 cechują się bardziej zaznaczonym przerostem lewej komory serca. (Diabet. Prakt. 2011, tom 12, nr 4, 134&#8211;141)INTRODUCTION. The aim of this study was to assess the influence of obesity and diabetes mellitus on left ventricular hypertrophy in patients with arterial hypertension. MATERIAL AND METHODS. Study population consisted of 554 patients with hypertension (62% men, 38% women), and 97 patients with hypertension and concomitant diabetes mellitus (DM) (61% men, 39% women). The mean age in these two groups was 53 &#177; 13 years v. 58 &#177; 8 years respectively. We performed echocardiography as well as blood pressure (twice) and waist and hip circumference measurements. Body mass index (BMI) was assessed. RESULTS. Left ventricular mass (LVM) and left ventricular mass index (LVMI) were significantly higher in the group with hypertension and concomitant DM than in the group without DM, LVM &#8212; 280.6 &#177; 67.4 g v. 247.3 &#177; 74.8 g, p < 0.0001, LVMI &#8212; 145.2 &#177; 33 g/m2 v. 129.9 &#177; 36 g/m2, p < < 0.0001. In patients with hypertension without DM, BMI positively correlated with LVMI (r = 0.17, p < < 0,0001) in men and in women. Waist/hip ratio positively correlated with LVMI in women (r = 0.26, p < 0.0001). In the group of patients with concomitant DM, BMI and waist/hip ratio didn&#8217;t correlate with left ventricular hypertrophy. CONCLUSIONS. Higher body mass index and abdominal obesity in women are risk factors for left ventricular hypertrophy. Left ventricular hypertrophy is more prevalent in the group with concomitant DM. (Diabet. Prakt. 2011, vol. 12, no 4, 134&#8211;141

Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests

High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study

Badanie możliwości związków koordynacyjnych opartych na tetrazolach

W ramach badań związanych z pracą zostały przeprowadzone syntezy, badania fotofizyczne oraz strukturalne związków koordynacyjnych opartych na ligandach tetrazolowych. Ligandy zostały wybrane na podstawie ich szczególnych właściwości luminescencyjnych w związkach z Re(I), Ru(II), Nd(III) i Eu(III). Dobór takich metali centralnych był motywowany ich potencjalnymi zastosowaniami w urządzeniach emitujących oraz pochłaniających promieniowanie z zakresu światła widzialnego i podczerwieni. Uzyskane wyniki wskazują na otrzymanie związków kompleksów o pożądanych właściwościach luminescencyjnych.Researches connected with thesis concerned: syntheses, photophysical and structural investigations of coordination compounds containing rich nitrogen ligands. Selected ligands were tetrazolato-based molecules, whereas metal used in construction of luminescence coordination complexes were Re(I), Ru(II), Nd(III) and Eu(III). Such selections of metals were supported by their interesting photophysical properties and possible applications as a light-emitting or light-harvesting devices. Obtained results shown that synthesized complexes have eligible luminescence properties

The Influence of Selected Antipsychotic Drugs on Biochemical Aspects of Alzheimer&rsquo;s Disease

The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide (PIM), quetiapine (QUET) and promazine (PROM)) on the main pathological hallmarks of Alzheimer&rsquo;s disease (AD). Binary mixtures of donepezil and antipsychotics produce an anti-BuChE effect, which was greater than either compound alone. The combination of rivastigmine and antipsychotic drugs (apart from PNF) enhanced AChE inhibition. The tested antipsychotics (excluding HAL and PNF) significantly reduce the early stage of A&beta; aggregation. BRMP, PIM, QUET and PROM were found to substantially inhibit A&beta; aggregation after a longer incubation time. A test of human erythrocytes hemolysis showed that short-term incubation of red blood cells (RBCs) with QUET resulted in decreased hemolysis. The antioxidative properties of antipsychotics were also proved in human umbilical vein endothelial cells (HUVEC); all tested drugs were found to significantly increase cell viability. In the case of astrocytes, BNP, PNF, PIM and PROM showed antioxidant potential