Iron metabolism disturbance as a marker of the severity of pathology in resuscitation patients

Forty-eight patients of resuscitation wards were examined, including 15 patients with purulent peritonitis, 12 patients with acute pancreatitis, 11 patients with thermal skin damages, and 10 patients with severe acetic acid intoxication. An increase in the serum iron, ferritin, and free hemoglobin contents of blood plasma influenced the severity of endotoxicosis. This was expressed in progressive fever, increase in the leukocytic intoxication index and concentrations of low-and middle-molecular-weight substances on erythrocytes and in the blood plasma, intensification of lipid peroxidation, and insufficiency of the antioxidant defense system, which resulted in the development of multiple organ failure in patients with the above-mentioned diseases.     

Transport of calcium to synaptosomes and subcellular membrane fractions of the brain: effects of opioid peptides

Highly purified synaptosomal and subcellular fractions identified as mitochondria and microsomes were obtained by fractionation of brain tissues. The greatest Ca-accumulating capacity and the highest rate of Ca2+ accumulation were revealed in the mitochondrial fraction. Upon further fractionation of the synaptosomal fraction the energy-dependent uptake (accumulation) of Ca2+ was revealed only in the mitochondria. It was demonstrated that opioid peptides accelerate Ca2+ uptake by the synaptosomes in a medium with physiological concentration of K+ and inhibit this process during K+-dependent membrane depolarization. It was shown that beta-endorphine, methionine-encephaline and leucine-encephaline (10(-8)-10(-5) M) inhibit the Ca-accumulating capacity of both mitochondria and microsomes from brain. The experimental data suggest that opioid peptides can modulate the release of neurotransmitters and/or neurohormones by inhibiting the potential-dependent Ca2+ influx into the nerve endings and by decreasing the intrasynaptosomal pool of Ca2+.     

A new species of the genus Theloderma Tschudi, 1838(Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau,central Vietnam

A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological,molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes:(1) bony ridges on head absent;(2) smooth skin completely lacking calcified warts or asperities;(3) pointed elongated tapering snout;(4) vocal opening in males absent;(5) vomerine teeth absent;(6) males of small body size(SVL 21.8–26.4 mm);(7) head longer than wide;ED/SVL ratio 13%–15%; ESL/SVL ratio 16%–20%;(8)small tympanum(TD/EL ratio 50%–60%) with few tiny tubercles;(9) supratympanic fold absent;(10) ventral surfaces completely smooth;(11) webbing between fingers absent;(12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape;(13) toes half-webbed:Ⅰ 2–2? Ⅱ 1?–2? Ⅲ 2–3? Ⅳ 3–1? Ⅴ;(14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent;(15) iris bicolored;(16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots;(17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearlyseparated from lighter dorsal coloration by straight contrasting edge;(18) ventral surfaces of body, throat,and chest greyish-blue with indistinct brown confluent blotches;(19) upper eyelids with few(3–5) very small flat reddish superciliary tubercles;(20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12 S rRNA to 16 S rRNA mitochondrial DNA fragment sequences(uncorrected genetic distance P8.9%). Advertisement call and tadpole morphology of the new species are described.Our molecular data showed Theloderma auratum sp. nov. to be a sister species of Th. palliatum from Langbian Plateau in southern Vietnam.     

Biomarkers of toxicity in Clarias gariepinus exposed to sublethal concentrations of polycyclic aromatic hydrocarbons

Physiological, biochemical and histological indices in Clarias gariepinus broodstock, and teratogenic indices in embryos exposed to sublethal concentrations of naphthalene, phenanthrene and pyrene were investigated in 2014 using a static-renewal bioassay protocol. Phenanthrene (1.41 mg l^?1) was the most toxic, followed by pyrene (1.53 mg l^?1) and naphthalene (7.21 mg l^?1), based on 96 h LC50 values. Hepatosomatic indices were significantly higher in naphthalene- and pyrene-treated males compared with solvent controls, whereas fecundity in females was significantly lower by factors of 2.4 (naphthalene), 2.8 (phenanthrene) and 2.4 (pyrene), compared with controls. Catalase levels were lower in female phenanthrene-treated fish compared with controls. Histological alterations observed in PAH-treated fish include oedema, inflammatory cells, epithelial lifting and hyperplasia in the gills, vacuolation, haemosiderin pigments and sinusoidal congestion in the liver, and degenerated zona radiata in the ovary. Teratogenic effects were not observed, as evidenced by the lack of histological alterations in embryos spawned from pre-exposed broodstock. Sex-specific responses and the utility of biomarkers at cellular and individual levels of organisation are therefore demonstrated for holistic evaluations of polycyclic aromatic hydrocarbons in ecotoxicological studies.     

The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration

Integrin β3 is seen as a key anti‐angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro‐ or anti‐angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3‐dependent adhesome. We show that depletion of β3‐integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3‐integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2‐driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced.     

Activation of Multimodal Areas in the Human Cerebral Cortex in Response to Biological Motion Sounds

Functional magnetic resonance imaging (fMRI) was used to investigate activation of the multimodal areas in the cerebral cortex–supramarginal and angular gyri, precuneus, and middle temporal visual cortex (MT/V5)–in response to motion of biologically significant sounds (human footsteps). The subjects listened to approaching or receding footstep sounds during 45 s, and such stimulation was supposed to evoke auditory adaptation to biological motion. Listening conditions alternated with stimulation-free control. To reveal activity in the regions of interest, the periods before and during stimulation were compared. Most stable and voluminous activation was detected in the supramarginal and angular gyri, being registered for all footstep sound types–approaching, receding and steps in place. Listening to human approaching steps activated the precuneus area, with the volume of activation clusters varying considerably between subjects. In the MT/V5 area, activation was revealed in 5 of 21 subjects. The involvement of the tested multimodal cortical areas in analyzing biological motion is discussed.     

Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3.

Intracellular signaling pathways that are involved in protection of vascular smooth muscle cells (VSMC) from apoptosis remain poorly understood. This study examines the effect of activators of cAMP/cGMP signaling on apoptosis in non-transfected VSMC and in VSMC transfected with c-myc (VSMC-MYC) or with its functional analogue, E1A-adenoviral protein (VSMC-E1A). Serum-deprived VSMC-E1A exhibited the highest apoptosis measured as the content of chromatin and low molecular weight DNA fragments, phosphatidylserine content in the outer surface of plasma membrane and caspase-3 activity (ten-, five-, four- and tenfold increase after 6 h of serum withdrawal, respectively). In VSMC-E1A, the addition of an activator of adenylate cyclase, forskolin, abolished chromatin cleavage, DNA laddering, caspase-3 activation and the appearance of morphologically-defined apoptotic cells triggered by 6 h of serum deprivation. In non-transfected VSMC and in VSMC-MYC, 6 h serum deprivation led to approximately six- and threefold activation of chromatin cleavage, respectively, that was also blocked by forskolin. In VSMC-E1A, inhibition of apoptosis was observed with other activators of cAMP signaling (cholera toxin, isoproterenol, adenosine, 8-Br-cAMP), whereas 6 h incubation with modulators of cGMP signaling (8-Br-cGMP, nitroprusside, atrial natriuretic peptide, L-NAME) did not affect the development of apoptotic machinery. The antiapoptotic effect of forskolin was abolished in 24 h of serum deprivation that was accompanied by normalization of intracellular cAMP content and protein kinase A (PKA) activity. Protection of VSMC-E1A from apoptosis by forskolin was blunted by PKA inhibitors (H-89 and KT5720), whereas transfection of cells with PKA catalytic subunit attenuated apoptosis triggered by serum withdrawal. The protection of VSMC-E1A by forskolin from apoptosis was insensitive to modulators of cytoskeleton assembly (cytochalasin B, colchicine). Neither acute (30 min) nor chronic (24 h) exposure of VSMC to forskolin modified basal and serum-induced phosphorylation of the MAP kinase ERK1/2. Thus, our results show that activation of cAMP signaling delays the development of apoptosis in serum-deprived VSMC at a site upstream of caspase-3 via activation of PKA and independently of cAMP-induced reorganization of the cytoskeleton network and the ERK1/2-terminated MAPK signaling cascade.     

Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3.

Long term elevation of the intracellular Na+/K+ ratio inhibits macromolecule synthesis and proliferation in the majority of cell types studied so far, including vascular smooth muscle cells (VSMC). We report here that inhibition of the Na+,K+ pump in VSMC by ouabain or a 1-h preincubation in K+-depleted medium attenuated apoptosis triggered by serum withdrawal, staurosporine, or okadaic acid. In the absence of ouabain, both DNA degradation and Caspase-3 activation in VSMC undergoing apoptosis were insensitive to modification of the extracellular Na+/K+ ratio as well as to hyperosmotic cell shrinkage. In contrast, protection of VSMC from apoptosis by ouabain was abolished under equimolar substitution of Na+o with K+o, showing that the antiapoptotic action of Na+,K+ pump inhibition was caused by inversion of the intracellular Na+/K+ ratio. Unlike VSMC, the same level of increment of the [Na+]i/[K+]i ratio caused by a 2-h preincubation of Jurkat cells with ouabain did not affect chromatin cleavage and Caspase-3 activity triggered by treatment with Fas ligand, staurosporine, or hyperosmotic shrinkage. Thus, our results show for the first time that similar to cell proliferation, maintenance of a physiologically low intracellular Na+/K+ ratio is required for progression of VSMC apoptosis.