Differential regulation of extracellular matrix constituents in myocardial remodeling with and without heart failure following pressure overload

Patients with aortic stenosis develop various degrees of myocardial hypertrophy and heart failure (HF) despite comparable transvalvular gradients. An important element in the transition from compensated hypertrophy to HF is dilatation of the left ventricle (LV). The molecular pathology associated with LV dilatation and development of HF is not known. Thus, we examined potential differences in the regulation of myocardial extracellular matrix (ECM) constituents in mice with hypertrophy only (ABnonHF) and with HF (ABHF) as response to comparable pressure overload. The ascending aorta was banded, or left loose in sham-operated mice. Increased lung weight and left atrial diameter indicating pulmonary congestion were used to identify ABHF mice. Cardiac function and geometry were evaluated by echocardiography. Despite comparable pressure gradients and cardiac output, ABHF had reduced fractional shortening (23%), reduced systolic (28%) and diastolic (32%) tissue velocity and increased LV internal dimension in diastole (10%) and systole (17%) (LVIDd/s) compared to ABnonHF (p ≤ 0.05). Microarray analyses identified 120 differently regulated genes related to ECM in ABHF compared to ABnonHF (p ≤ 0.05). Interestingly, in ABHF, we found a 24% (p ≤ 0.05) reduction of the LV collagen VIII protein levels despite increased levels of LV total collagen by 23% (p ≤ 0.05). LV collagen VIII correlated negatively with LVIDd (R = 0.55, p = 0.03) and LVIDs (R = 0.72, p = 0.002). As this protein may function as a “sealant” binding collagen fibrils together, reduction of collagen VIII could potentially contribute to LV dilatation and development of HF.     

A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure–activity relationships

A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior.     

Cross-sectional study of ocular optical components interactions in emmetropes

Purpose of the paper was to evaluate ocular optical components (OOC) interactions in a large number of emmetropes. A cross-sectional study of 1,000 emmetropes, aged from 18-40 years, has been conducted. Complete ophthalmological examination, corneal radius (CR) measurement, keratometry and echobiometry of both eyes were performed. The highest correlation of OOC was that of axial length (Ax) with vitreal body (CV) on both eyes (r = 0.79 for the right eye (RE); r = 0.81 for the left eye (LE)). The axial length had a positive correlation with the anterior chamber depth (ACD) on both eyes as well, but the coefficient was very low (r = 0.29 for the RE; r = 0.32 for the LE). The only negative correlation Ax had on both eyes was with the lens (L) (r = -0.17 for the RE; r = -0.19 for the LE). Keratometry of the horizontal (K1) and vertical meridian (K2) showed a negative correlation with CV and Ax on both eyes (for K1 r = -0.64 for CV r = -0.54 for Ax; for K2 r = -0.67 for CV r = -0.68 for Ax). CR had a positive correlation with Ax (r = 0.74) and CV (r = 0.79). It showed a negative correlation with L (r = -0.58). CV had a high, positive correlation with Ax (r = 0.72 for the RE; r = 0.75 for the LE). The correlation with K1 and K2 was negative. Our study showed that the axial length, keratometry, corneal radius, lens thickness and vitreal body were the most important OOC that correlated with each other following a pattern in our group of emmetropes. They interacted in such a way that in the subjects with axial length above the average value, the vitreal body was longer but the lens was thinner and the cornea was of less power. This could explain at least one of the mechanisms of emmetropization.     

Exploring immunogenicity of tick salivary AV422 protein in persons exposed to ticks: prospects for utilization

Experimental and Applied Acarology - In order to determine whether conserved tick salivary protein AV422 is immunogenic, the goal of our study was to detect specific IgG response within at-risk...     

The impact of the flower mite Aceria acroptiloni on the invasive plant Russian knapweed,Rhaponticum repens,in its native range

Rhaponticum repens (L.) Hidalgo is a clonal Asteraceae plant native to Asia and highly invasive in North America. We conducted open-field experiments in Iran to assess the impact of the biological control candidate, Aceria acroptiloni Shevchenko & Kovalev (Acari, Eriophyidae), on the target weed. Using three different experimental approaches, we found that mite attack reduced the biomass of R. repens shoots by 40–75 %. Except for the initial year of artificial infestation by A. acroptiloni of R. repens shoots, the number of seed heads was reduced by 60–80 % and the number of seeds by 95–98 %. Morphological investigations of the mite complex attacking R. repens at the experimental field site revealed that A. acroptiloni was by far the dominant mite species. We conclude that the mite A. acroptiloni is a promising biological control candidate inflicting significant impact on the above-ground biomass and reproductive output of the invasive plant R. repens.     

Essential‐Oil Composition of the Needles Collected from Natural Populations of Macedonian Pine (Pinus peuce Griseb.) from the Scardo‐Pindic Mountain System

The needle‐terpene profiles of two natural Pinus peuce populations from the Scardo‐Pindic mountain system (Mt. O?ljak and Mt. Pelister) were analyzed. Among the 90 detected compounds, 87 were identified. The dominant constituents were α‐pinene (45.5%), germacrene D (11.1%), β‐pinene (10.8%), and camphene (10.3%). The following eight additional components were found to be present in medium‐to‐high amounts (0.5–10%): bornyl acetate (5.0%), β‐phellandrene (3.4%), β‐caryophyllene (2.9%), β‐myrcene (0.9%), germacrene D‐4‐ol (0.9%), tricyclene (0.7%), (E)‐hex‐2‐enal (0.7%), and bicyclogermacrene (0.6%). Although the general needle‐terpene profiles of the populations from Mt. O?ljak and Mt. Pelister were found to be similar to those of the populations from Zeletin, Sjekirica, and Mokra Gora (Dinaric Alps), principle component analysis (PCA) of eight terpenes (α‐pinene, β‐myrcene, α‐terpinolene, bornyl acetate, α‐terpinyl acetate, β‐caryophyllene, trans‐β‐farnesene, and germacrene D) in 139 tree samples suggested a divergence between the two population groups, i.e., the samples from the Scardo‐Pindic mountain system and those from the Dinaric Alps. Genetic analysis of the β‐pinene content demonstrated a partial divergence between the two geographical groups. The profiles of both population groups differed from those published for populations from the Balkan‐Rhodope mountains system (literature results), which were characterized by high contents of bornyl acetate and citronellol (Greek populations) or δ‐car‐3‐ene (Bulgarian populations).     

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells

We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy.     

Removal of water turbidity by natural coagulants obtained from chestnut and acorn

The ability of seed extracts of several species of chestnut and acorn to act as natural coagulants was tested using a synthetic turbid water. Active components were extracted from ground seeds of Horse chestnut and acorns of some species of family Fagaceae: Common oak, Turkey oak, Northern red oak and European chestnut. All investigated extracts had coagulation capabilities and their amounts depended on pH values and initial turbidities. The seed extracts from European chestnut and Common oak acorn were the most efficient expressing the highest coagulation activities, about 80% and 70%, respectively, in both low and medium investigated water turbidities at the lowest coagulant dose 0.5 ml/L.     

Influence of lipid metabolism disorders on venous thrombosis risk

Background: To investigate the influence of lipid metabolism disorders on the risk of deep vein thrombosis. Methods: A total of 200 subjects participated in the study, 100 of whom experienced DVT with or without PTE, and 100 healthy subjects representing the control group. We classified patients and controls in terms of serum concentrations of chylomicrons, LDL, IDL, VLDL, and HDL particles, as those with or without hyperlipoproteinemia and in terms of serum Lp (a) lipoprotein levels, as those with hyperLp (a) lipoproteinemia (serum Lp (a) values >0.3 g/L) and those without hyperLp (a) lipoproteinemia (serum Lp (a) values <0.3 g/L). Based on the modified and supplemented Fredrickson classification, participants with verified existences of hyperlipoproteinemia were classified into subgroups based on the type of hyperlipoproteinemia. Unconditional logistic regression was used to calculate ORs with 95% CIS as a measure of the relative risks for venous thrombosis in participants with hyperlipoproteinemia compared with those without hyperlipoproteinemia. The analysis was adjusted for all potential confounders (age, sex, obesity) related to the functionality of the lipid metabolism, and at the same time, may have an impact on the risk of venous thrombosis. Results: The results of the comparison of the mean values of individual lipid status parameters between the patient group and the control group clearly indicate higher concentrations of total cholesterol (5.93 mmol/L vs. 5.52 mmol/L), total triglycerides (1.58 mmol/L vs. 1.50 mmol/L), and LDL-cholesterol (3.83 mmol/L vs. 3.44 mmol/L) in the patient group relative to the control group, with a statistically significant difference observed only in the case of LDL-cholesterol concentrations. We have found that type IIa hyperlipoproteinemia is associated with a nearly double increased risk for deep vein thrombosis (OR 1.99; Cl 1.01-3.90), while type IIb, IV, or hyperLp (a) lipoproteinemia did not influence the risk (OR 1.22; 95% Cl 0.79-1.84; OR 0.89; 95% Cl 0.52-1.54 OR 1.85; 95% CI 0.84-4.04). Conclusions: Hypercholesterolemia doubles the risk of deep vein thrombosis development.