Effects of different dietary fatty acids profiles on the growth performance and body composition of juvenile tench (<Emphasis Type="Italic">Tinca tinca</Emphasis> (L.))

Juvenile tench (initial weight of about 57 g) were fed feed supplemented with fish oil (group FO), linseed oil (group LO), peanut oil (group PO), or rapeseed oil (group RO) containing 47% protein and 12% fat for 55 days. The inclusion of the tested oils was 50 g kg⁻¹ (42% total crude lipids in diets). No significant differences were noted in the fish growth performance. The proximate composition of the whole fish bodies and the viscera (water, protein, fat, ash) was similar in all the dietary treatments (P > 0.05). Differences were noted only with regard to the ash content of the fillets (P < 0.05). The analysis of the fatty acids profiles of tench (whole fish) indicated there were significant differences in the total content of monoenoic and polyenoic (PUFA) acids. Significant differences were also noted with regard to n-3 PUFA and n-6 PUFA. Consequently, the ratio of n-3/n-6 acids ranged from 1.6 (group PO) to 2.08 (group LO; P < 0.05). The feed applied was not confirmed to have had an impact on the fatty acids profile of the tench fillets. There was a statistically significant intergroup difference in the content of saturated fatty acids (SFA) in tench viscera. In the fish fed vegetable oils supplemented diets, the level of SFA was lower (P < 0.05).     

The in vitro effect of new muramyl peptide derivatives on cytotoxic activity of NK (Natural Killer) cells from hamsters bearing AB Bomirski Melanoma

The modulation of NK activity by muramyl dipeptides derivatives against Ab (amelanotic) Bomirski melanoma and human erythroleukemia K562 cells was studied in vitro. The stimulatory effect was observed for 3 of 7 muramyl dipeptides: MDP(L-Ala)C921, MDPC857 and L18-MDP(Ala) in relation to cytotoxic activity of NK cells obtained from peripheral blood and spleen of healthy and Ab Bomirski melanoma bearing hamsters. An increased of cytotoxic activity NK cells isolated from animals before and during the transplantable phase of the tumor against K562 was found. A similar stimulation was received for NK cells obtained from animals against their own melanoma cells. The most significant influence of examined MDP derivatives on the cytotoxic activity of NK cells were obtained from animals between 10 to 12 days of tumor growth. The extent of the modulation of cytotoxic activity of NK cells was dependent on its initial value both in healthy control and Ab Bomirski melanoma bearing hamsters. If natural cytotoxic activity was high the stimulatory effect of the examined MDP derivatives was only slightly expressed.     

GRACE Score among Six Risk Scoring Systems (CADILLAC,PAMI, TIMI,Dynamic TIMI,Zwolle) Demonstrated the Best Predictive Value for Prediction of Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction

Aim

To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients.

Methods and Results

A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores—the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE—showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73–0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80–0.83).

Conclusions

All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model.     

Pharmacological profile of the "triple" monoamine neurotransmitter uptake inhibitor, DOV 102,677

1. The molecular and behavioral pharmacology of DOV 102,677 is characterized. 2. This characterization was performed using radioligand binding and neurotransmitter uptake assays targeting the monoamine neurotransmitter receptors. In addition, the effects of DOV 102,677 on extracellular neurotransmitter levels were investigated using in vivo microdialysis. Finally, the effects of DOV 102,677 in the forced swim test, locomotor function, and response to prepulse inhibition was investigated.3. DOV 102,677 is a novel, "triple" uptake inhibitor that suppresses [(3)H]dopamine (DA), [(3)H]norepinephrine (NE) and [(3)H]serotonin (5-HT) uptake by recombinant human transporters with IC(50) values of 129, 103 and 133 nM, respectively. Radioligand binding to the dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters is inhibited with k (i) values of 222, 1030, and 740 nM, respectively. DOV 102,677 (20 mg/kg IP) increased extracellular levels of DA and 5-HT in the prefrontal cortex to 320 and 280% above baseline 100 min after administration. DA levels were stably increased for the duration (240 min) of the study, but serotonin levels declined to baseline by 200 min after administration. NE levels increased linearly to a maximum of 348% at 240 min post-dosing. Consistent with these increases in NE levels, the density of beta-adrenoceptors was selectively decreased in the cortex of rats treated with DOV 102,677 (20 mg/kg per day, PO, 35 days). 4. DOV 102,677 dose-dependently reduced the amount of time spent immobile by rats in the forced swim test, a model predictive of antidepressant activity, with a minimum effective dose (MED) of 20 mg/kg and a maximal efficacy comparable to imipramine. This decrease in immobility time did not appear to result from increased motor activity. Further, DOV 102,677 was as effective as methylphenidate in reducing the amplitude of the startle response in juvenile mice, without notably altering motor activity. 5. In summary, DOV 102,677 is an orally active, "balanced" inhibitor of DAT, NET and SERT with therapeutic versatility in treating neuropsychiatric disorders beyond depression.     

Reduction of lamin B receptor levels by miR-340-5p disrupts chromatin,promotes cell senescence and enhances senolysis

A major stress response influenced by microRNAs (miRNAs) is senescence, a state of indefinite growth arrest triggered by sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as a novel miRNA that foments cellular senescence. miR-340-5p was highly abundant in diverse senescence models, and miR-340-5p overexpression in proliferating cells rendered them senescent. Among the target mRNAs, miR-340-5p prominently reduced the levels of LBR mRNA, encoding lamin B receptor (LBR). Loss of LBR by ectopic overexpression of miR-340-5p derepressed heterochromatin in lamina-associated domains, promoting the expression of DNA repetitive elements characteristic of senescence. Importantly, overexpressing miR-340-5p enhanced cellular sensitivity to senolytic compounds, while antagonization of miR-340-5p reduced senescent cell markers and engendered resistance to senolytic-induced cell death. We propose that miR-340-5p can be exploited for removing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in pathologies of human aging.     

Thioridazine induces erythrocyte stomatocytosis due to interactions with negatively charged lipids

Despite the fact that thioridazine is used clinically as a neuroleptic drug, little is known about the molecular mechanisms underlying its biological effects, in particular about its interactions with membranes. In the present work we investigate the influence of thioridazine on model and cell membranes, using calorimetry, DPH fluorescence polarization measurements, studies of haemolysis and scanning electron microscopy. The experiments show that thioridazine interacts with lipid bilayers and intercalates into bilayer structure. We found that erythrocyte stomatocytosis induced by the drug might be related to preferential interaction of thioridazine with charged lipids.     

Nijmegen breakage syndrome (NBS)

Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alstr?m disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.