Flavone Derivatives as Inhibitors of Insulin Amyloid-Like Fibril Formation

Several natural and synthetic flavone derivatives have been reported to inhibit formation of amyloid fibrils or to remodel existing fibrils. These studies suggest that the numbers and positions of hydroxyl groups on the flavone rings determine their effectiveness as amyloid inhibitors. In many studies the primary method for determining the effectiveness of inhibition is measuring Thioflavin T (ThT) fluorescence. This method demonstrably results in a number of false positives for inhibition. We studied the effects of 265 commercially available flavone derivatives on insulin fibril formation. We enhanced the effectiveness of ThT fluorescence measurements by fitting kinetic curves to obtain halftime of aggregation (t ₅₀). Maximal values of ThT fluorescence varied two fold or more in one third of all cases, but this did not correlate with changes in t ₅₀. Changes in t ₅₀ values were more accurate measures of inhibition of amyloid formation. We showed that without a change in an assay, but just by observing complete kinetic curves it is possible to eliminate numbers of false positive and sometimes even false negative results. Examining the data from all 265 flavones we confirmed previous observations that identified the importance of hydroxyl groups for inhibition. Our evidence suggests the importance of hydroxyl groups at locations 5, 6, 7, and 4’, and the absence of a hydroxyl group at location 3, for inhibiting amyloid formation. However, the main conclusion is that the positions are not additive. The structures and their effects must be thought of in the context of the whole molecule.     

3D cellular spheroids as tools for understanding carboxylated quantum dot behavior in tumors

Background

Monolayer cell cultures have been considered the most suitable technique for in vivo cellular experiments. However, a lot of cellular functions and responses that are present in natural tissues are lost in two-dimensional cell cultures. In this context, nanoparticle accumulation data presented in literature are often not accurate enough to predict behavior of nanoparticles in vivo. Cellular spheroids show a higher degree of morphological and functional similarity to the tissues.

Trends in the Attack Rates,Incidence, and Mortality of Stroke during 1986–2012: Data of Kaunas (Lithuania) Stroke Registry

BackgroundThere is a lack of reliable epidemiological data on longitudinal trends in stroke attack rates, incidence, and mortality in the countries of the Baltic region.AimsThe aim of the present study was to explore the longitudinal trends of stroke in middle-aged urban population of Lithuania during the period of 1986 through 2012.MethodsAll stroke events in the studied population were ascertained and validated according to the standardized criteria outlined by the WHO MONICA Project. The study included all patients in Kaunas (Lithuania) city aged 25 to 64 years who experienced a stroke between 1986 and 2012. Estimates of time-trends of the annual percentage change in stroke attack rates, incidence of stroke, and mortality from this condition were made by applying the Joinpoint regression analysis.ResultsDuring the study period, 9,992 stroke events were registered. The overall proportion of recurrent events was 25.7%. Overall, 18.9% of the events (20.0% in men, and 17.4% in women) were fatal within 28 days. During the period of 1986 to 2012, a flat trend in the incidence of stroke was observed among both male and female middle-aged inhabitants of Kaunas city, while attack rates were increasing due to the increase in recurrent strokes. Both mortality and 28-day case fatality of stroke declined significantly over the study period in both sexes.ConclusionsAn increase both in the incidence and recurrence of stroke among middle-aged men residing in Kaunas city and in the recurrence of stroke among women denotes the inefficiency of measures applied both for primary and secondary prevention of stroke in Lithuania. The revision of current prevention strategies and the introduction of new ones are of paramount importance in order to fight the epidemic of stroke.     

Examination of the stability of hydrophobic (CdSe)ZnS quantum dots in the digestive tract of rats.

Semiconductor quantum dots show promise as alternatives to organic dyes for biological labelling because of their bright and stable photoluminescence. The typical quantum dots is CdSe because colloidal synthesis for nanocrystals of this semiconductor is well established. CdSe is usually passivated with zinc sulfide. While the cytotoxicity of bulk CdSe is well documented, questions about (CdSe)ZnS potential toxicity and behaviour in vivo remain unanswered. The distribution and stability of (CdSe)ZnS quantum dots in Wistar line rats' digestive tract were investigated. Hydrophobic quantum dots were mixed with fat or sonificated in water and administered orally. The distribution and stability of quantum dots moving through the digestive system of rats was followed by fluorescence spectroscopy. In both ways prepared quantum dots were degraded in the digestive tract of animals. Quantum dots mixed with fat were more stable and degraded more slowly than quantum dots sonificated in water. The data obtained suggest possible toxicity of (CdSe)ZnS quantum dots due to the liberation of Cd(2+).     

Smoking and other risk factors for pancreatic cancer: A cohort study in men in Lithuania

Background: Cancer of the pancreas is a relatively rare, but highly fatal cancer worldwide. Cigarette smoking has been recognized as an important risk factor, but the relation to other potential determinants is still inconsistent. We investigated the association between different lifestyle, biological and anthropometric factors and the risk of pancreatic cancer in a prospective population-based cohort study from Kaunas, Lithuania. Methods: Our study included 7132 urban men initially free from any diagnosed cancer, followed for up to 30 years. 77 incident cases of pancreatic cancer were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Compared to never smokers, current smokers had a significantly increased risk of pancreatic cancer, HR was 1.79 (95% CI 1.03–3.09) after adjustment for age, body mass index, education and alcohol consumption. Among smokers, a significant association with higher smoking intensity was shown (≥20 cigarettes/day: HR = 2.60; 95% CI 1.42–4.76, P_trend = 0.046). We also observed a significantly increased risk for ≥30 pack-years of smoking (HR = 2.24; 95% CI 1.12–4.49, P_trend = 0.16) and for age at starting smoking <18 years (HR = 2.29; 95% CI 1.11–4.70, P_trend = 0.43) as compared to never smokers. Alcohol consumption, body mass index and total cholesterol level were not significantly associated with pancreatic cancer. Conclusions: Smoking significantly increases pancreatic cancer incidence and its high prevalence in Lithuania may partly explain high incidence of the disease. No convincing evidence was found that alcohol consumption, body mass index or serum cholesterol level were associated with pancreatic cancer risk, although the assessment was limited by the lack of statistical power.     

Spectroscopic study of ALA-induced endogenous porphyrins in arthritic knee tissues: targeting rheumatoid arthritis PDT.

The inflamed synovium of rheumatoid arthritis exhibits many features typical for neoplastic tissue implying that the photodynamic therapy might be an efficient modality for chronic poliarthritis. The accumulation of endogenously produced porphyrins after administration of exogenous 5-aminolevulinic acid (ALA) in a rabbit model of rheumatoid arthritis was evaluated by fluorescence spectroscopy. Independent of the way, intravenously or intra-articularly, in which ALA was administered to the experimental animals, the highest fluorescence intensity of endogenously produced porphyrins was detected in the tissues of the inflamed joints. Besides, the application of ALA had a systemic sensitising effect on the whole organism of rabbits. The highest amount of endogenously produced porphyrins in the inflamed joints measured from the surface of the skin above the synovium tissues was detected 1-3 h after the administration of ALA. Fluorescence measurements performed on the tissue specimens ex vivo showed the predominant accumulation of porphyrins in the synovium of the inflamed joints. The fluorescence of porphyrins was also observed in the cartilage tissues taken from knee joints. However, the fluorescence spectra features indicated that the composition of porphyrins detected in the cartilage tissues was different than that in the synovial tissues. The selective accumulation of porphyrins in the inflamed synovial tissues stands up for the application of photodynamic therapy in the treatment of rheumatoid arthritis and implies the possibility to use optical non-invasive methods based on fluorescence detection of endogenously produced porphyrins for diagnostics of inflamed tissues.     

Spectroscopic study of TPPS4 nanostructures in the presence of bovine serum albumin.

The influence of bovine serum albumin (BSA) on the formation of J-aggregates of meso-tetra(4-sulfonatophenyl)porphine (TPPS4) in aqueous acid solution (pH 1.3) has been investigated by means of absorption and fluorescence spectroscopy. TPPS4 concentration was kept constant at 2 microM while BSA concentration was varied to get TPPS4 : BSA molar ratios from 1 : 0.005 to 1 : 20. In the presence of protein at all used concentrations the intensity of J-aggregates absorption band was higher than that in the pure solution. Spectral changes indicated that the dynamic equilibrium of the aggregated TPPS4 species was highly dependent on the molar ratio between TPPS4 and BSA. Small relative concentrations of BSA (TPPS4 : BSA, 1 : 0.005-1 : 0.1) had a stimulating effect on formation of J-aggregates. Several fractions of J-aggregates located in protein and aqueous moieties were detected in mixed solutions at intermediate BSA concentrations (TPPS4 : BSA, 1 : 0.5-1 : 8), when the absorbance intensity of the J-aggregates was the highest. At the highest used BSA concentrations (TPPS4 : BSA, 1 : 10-1 : 20) the spectral properties of the remaining J-aggregates were similar to those typical for pure porphyrin solution. Additionally, the split of the Soret band into two with peaks at 440 nm and 423 nm was followed by the simultaneous appearance of Q bands and reflected the formation of TPPS4-BSA complexes including both protonated and deprotonated TPPS4 forms.     

The Prognostic Value of Family History for the Estimation of Cardiovascular Mortality Risk in Men: Results from a Long-Term Cohort Study in Lithuania

Aim

To evaluate the additional prognostic value of family history for the estimation of cardiovascular (CVD) mortality risk in middle-aged urban Lithuanian men.

Methods

The association between family history of CVD and the risk of CVD mortality was examined in a population-based cohort of 6,098 men enrolled during 1972–1974 and 1976–1980 in Kaunas, Lithuania. After up to 40 years of follow-up, 2,272 deaths from CVD and 1,482 deaths from coronary heart disease (CHD) were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for CVD and CHD mortality.

Results

After adjustment for traditional CVD risk factors, the HR for CVD mortality was 1.24 (95% CI 1.09–1.42) and for CHD mortality 1.20 (1.02–1.42) in men with first-degree relatives having a history of myocardial infarction (MI), compared to men without positive family history. A significant effect on the risk of CVD and CHD mortality was also observed for the family history of sudden cardiac death and any CVD. Addition of family history of MI, sudden death, and any CVD to traditional CVD risk factors demonstrated modest improvement in the performance of Cox models for CVD and CHD mortality.

Conclusions

Family history of CVD is associated with a risk of CVD and CHD mortality significantly and independently of other risk factors in a middle-aged male population. Addition of family history to traditional CVD risk factors improves the prediction of CVD mortality and could be used for identification of high-risk individuals.     

Cardiovascular risk factors and cognitive function in middle aged and elderly Lithuanian urban population: results from the HAPIEE study

Background

The purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.

Methods

Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.

Results

The scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR?=?2.52; 95% CI?=?1.75-3.64; in female OR?=?2.45; 95% CI?=?1.75, 3.64) as well as ischemic heart disease history (among male OR?=?1.28; 95% CI?=?1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR?=?1.32; 95% CI?=?1.03-1.69), poor self-rated health (among male OR?=?1.57; 95% CI?=?1.15-2.14) and poor quality of life (in male OR?=?1.67; 95% CI?=?1.07-2.61; in female OR?=?2.81; 95% CI?=?1.92-4.11) were related to lowered cognitive function.

Conclusions

The findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.