Serum endocan levels in relation to traditional and non-traditional anthropometric indices in adult population

BackgroundAssociation between endocan and nontraditional anthropometric indices, as distinct cardiovascular disease risk factors, has not been examined in previous studies. Endocan is a novel inflammation biomarker with its higher levels involved in cardiometabolic diseases development. Taking into consideration that obesity is an independent risk factor for many cardiometabolic diseases, we aimed to explore the relationship between endocan levels and novel anthropometric indices [i.e., body adiposity index (BAI), cardiometabolic index (CMI), a body shape index, body roundness index, conicity index, lipid accumulation product index and visceral adiposity index] and traditional ones [i.e., waist circumference, hip circumference, body mass index, waist-to-height ratio and waist-to-hip ratio] in adult population.MethodsA total of 177 participants were included. Anthropometric indices and biochemical parametres were measured.ResultsUnivariate regression analysis demonstrated positive correlations of endocan and almost all anthropometric data. To explore independent associations of endocan and anthropometric parameters, the Model which fulfilled criteria for ordinal regression testing was created. Adjusted odds for BAI given in the Model (OR=1.120, 95% CI 1.036-1.212, P=0.004), demonstrated that a rise in BAI by 1 unit increased the probability of higher endocan concentration by 12%. As well, a rise in CMI for 1 unit, increased the probability for higher endocan levels for 2.6 times (OR=2.599, 95% CI 1.006-6.712, P=0.049). A total of 20.1% of variation in endocan levels could be explained by this Model.ConclusionsNon-traditional obesity indices, BAI and CMI independently correlated with higher serum endocan levels in adult population.     

Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson's: an in vivo imaging study

Studies showed that the dopamine (DA) transporter (DAT) modulates changes in levodopa-derived synaptic dopamine levels (Δ(DA)) in Parkinson's disease (PD). Here we evaluate the relationship between DAT and Δ(DA) in the 6-hydroxydopamine model of Parkinson's disease to investigate these mechanisms as a function of dopaminergic denervation and in relation to other denervation-induced regulatory changes. 27 rats with a unilateral 6-hydroxydopamine lesion (denervation ∼20–97%) were imaged with ¹¹C-dihydrotetrabenazine (VMAT2 marker), ¹¹C-methylphenidate (DAT marker) and ¹¹C-raclopride (D2-type receptor marker). For denervation <75%Δ(DA) was significantly correlated with a combination of relatively preserved terminal density and lower DAT. For denervation <90%, Δ(DA) was significantly negatively correlated with DAT with a weaker dependence on VMAT2. For the entire data set, no dependence on pre-synaptic markers was observed; Δ(DA) was significantly positively correlated with ¹¹C-raclopride binding-derived estimates of DA loss. These findings parallel observations in humans, and show that (i) regulatory changes attempt to normalize synaptic DA levels (ii) a lesion-induced functional dependence of Δ(DA) on DAT occurs up to ∼ 90% denervation (iii) for denervation < 75% relative lower DAT levels may relate to effective compensation; for higher denervation, lower DAT levels likely contribute to oscillations in synaptic DA associated with dyskinesias.     

Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women

Recent human and animal studies have found associations between gut microbiota composition and serum levels of sex hormones, indicating that they could be an important factor in shaping the microbiota. However, little is known about the effect of regular hormonal fluctuations over the menstrual cycle or CHC-related changes of hormone levels on gut microbiota structure, diversity and dynamics. The aim of this study was to investigate the effect of CHCs on human gut microbiota composition. The effect of CHC pill intake on gut microbiota composition was studied in a group of seven healthy pre-menopausal women using the CHC pill, compared to the control group of nine age-matched healthy women that have not used hormonal contraceptives in the 6 months prior to the start of the study. By analysing the gut microbiota composition in both groups during one menstrual cycle, we found that CHC usage is associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. These results call for further investigation of the mechanisms underlying hormonal and hormonal contraceptive-related changes of the gut microbiota and the potential implications of these changes for women's health.     

Atrazine-induced degranulation of thyroid mast cells in peripubertal and adult rats

Atrazine is a commonly used pesticide in the US and the non-EU countries. It is classified as an endocrine-disrupting chemical and is well-known for its reproductive toxicity in mammals and lower vertebrates. The study on atrazine effects on thyroid mast cells was performed on juvenile/peripubertal and adult male Wistar rats orally gavaged with atrazine at doses of 50 mg/kg of body weight (bw) or 200 mg/kg bw. In order to visualize the mast cell population within the thyroid gland, a histochemical staining method of toluidine blue was used. The results of the histological evaluation demonstrated a prominent increase in mast cell degranulation in both age groups and at both atrazine doses. According to the stereological analysis, a statistically significant decrease in the mast cell volume density in the young rats exposed to a higher dose of atrazine was found when compared to the corresponding control. The numerical density of mast cells significantly decreased in a higher-dose atrazine treated adults in comparison to the control. The obtained data suggest that atrazine-affected mast cells would probably have a consequent influence on thyroid follicular cells and/or thyroid microvasculature via paracrine action of released mediators, but might also be involved in already suggested thyroid cancerogenesis.     

Radioprotectors – the Evergreen Topic

To protect organisms from ionizing radiation (IR), and to reduce morbidity or mortality, various agents, called radioprotectors, have been utilized. Because radiation‐induced cellular damage is attributed primarily to the harmful effects of free radicals, molecules with radical‐scavenging properties are particularly promising as radioprotectors. Early development of such agents focused on thiol synthetic compounds, known as WR protectors, but only amifostine (WR‐2721) has been used in clinical trials as an officially approved radioprotector. Besides thiol compounds, various compounds with different chemical structure were investigated, but an ideal radioprotector has not been found yet. Plants and natural products have been evaluated as promising sources of radioprotectors because of their low toxicity, although they exhibit an inferior protection level compared to synthetic thiol compounds. Active plant constituents seem to exert the radioprotection through antioxidant and free radical‐scavenging activities. Our research established that plants containing polyphenolic compounds (raspberry, blueberry, strawberry, grape, etc.) exhibit antioxidative activities and protect genetic material from IR.     

Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: Preliminary structure–activity relationship and pharmacophore modeling

Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice. Cembranoid 1 acts by noncompetitive inhibition of the α7 nicotinic acetylcholine receptor. This study aims at establishing a preliminary structure–activity relationship to define the neuroprotective cembranoid pharmacophores using the hippocampal slice assay and pharmacophore modeling. Fourteen natural, semisynthetic, or biocatalytic cembranoid analogues 2–15 related to 1 were tested for their capacity to protect the population spikes from DFP-induced damage and intrinsic toxicity. Twelve cembranoids caused significant reversal of DFP toxicity; only 3 active analogues displayed minor intrinsic toxicity at 10 μM. The C-4 epimer of 1 (2) and the 4-O-methyl ether analogue of 1 (3), were totally devoid of neuroprotective activity. The results suggested a model for cembranoid binding where the hydrophobic ring surface binds to a hydrophobic (Hbic) patch on the receptor molecule and an electronegative atom (oxygen or sulfur) in proper spatial relationship to the ring surface interacts with an electropositive group in the receptor binding site. A pharmacophore model consisting of 1 hydrogen bond acceptor (HBA), 2 Hbic, and 10 exclusion spheres was established using HipHop-REFINE and supported the above mentioned pharmacophoric hypothesis.     

Surface structure of the two porcine low-density lipoprotein subclasses — a spin labelling study

Porcine low-density lipoprotein (LDL) subclasses were spin-labelled at both protein and lipid sites. The surface structures of the two subclasses were compared. E.s.r. spectra of stearic acid spin-labels [I(m/n)] and of androstanol spin-label indicated more restricted motion of the labels in LDL₂ (d = 1.063?1.090 g/ml) than in LDL₁ (d = 1.020?1.063 g/ml). Thermotropic change in the surface structure was found in both subclasses by both protein and lipid spin-labels, but at lower temperature in LDl₁, than in LDL₂. These results indicate the relationship between the size and the dynamics of the lipid components in the surface layer of the LDL subclasses.     

Reinventing Biostatistics Education for Basic Scientists

Numerous studies demonstrating that statistical errors are common in basic science publications have led to calls to improve statistical training for basic scientists. In this article, we sought to evaluate statistical requirements for PhD training and to identify opportunities for improving biostatistics education in the basic sciences. We provide recommendations for improving statistics training for basic biomedical scientists, including: 1. Encouraging departments to require statistics training, 2. Tailoring coursework to the students’ fields of research, and 3. Developing tools and strategies to promote education and dissemination of statistical knowledge. We also provide a list of statistical considerations that should be addressed in statistics education for basic scientists.     

Temperature-dependent conformation change in spin-labeled hemoglobin

Hemoglobin was spin labeled at β-93(F9)-cysteine with N-oxy-2,2,6,6-tetramelhylpiperidinylmaleimide. The inward shift of the high-field hyperfine line (ΔH_XXX) position in the ESR spectra of the Spin label was measured aS a function of temperature. One can expect that an abrupt change in the microenvironment around the tightly bound spin label will be reflected in the function ΔH_XXX(T) as a discontinuity (break point). This was shown for aquo-, azido-. nitro- and oxyhemoglobin derivatives. The presented results suggest that the microenvironment around the tightly hound spin label in those methemoglobin derivatives that exhibit the mixed-spin state of the heme iron is prone to an abrupt change above a certain ligand-specific temperature. The change in microenvironment of the spin label is probably due to a temperature-dependent change in the tertiary structure of the protein.