Surfactant metabolism and anti-oxidative capacity in hyperoxic neonatal rat lungs: effects of keratinocyte growth factor on gene expression in vivo

Development of preterm infant lungs is frequently impaired resulting in bronchopulmoary dysplasia (BPD). BPD results from interruption of physiologic anabolic intrauterine conditions, the inflammatory basis and therapeutic consequences of premature delivery, including increased oxygen supply for air breathing. The latter requires surfactant, produced by alveolar type II (AT II) cells to lower surface tension at the pulmonary air:liquid interface. Its main components are specific phosphatidylcholine (PC) species including dipalmitoyl-PC, anionic phospholipids and surfactant proteins. Local antioxidative enzymes are essential to cope with the pro-inflammatory side effects of normal alveolar oxygen pressures. However, respiratory insufficiency frequently requires increased oxygen supply. To cope with the injurious effects of hyperoxia to epithelia, recombinant human keratinocyte growth factor (rhKGF) was proposed as a surfactant stimulating, non-catabolic and epithelial-protective therapeutic. The aim of the present study was to examine the qualification of rhKGF to improve expression parameters of lung maturity in newborn rats under hyperoxic conditions (85 % O₂ for 7 days). In response to rhKGF proliferating cell nuclear antigen mRNA, as a feature of stimulated proliferation, was elevated. Similarly, the expressions of ATP-binding cassette protein A3 gene, a differentiation marker of AT II cells and of peroxiredoxin 6, thioredoxin and thioredoxin reductase, three genes involved in oxygen radical protection were increased. Furthermore, mRNA levels of acyl-coA:lysophosphatidylcholine acyltransferase 1, catalyzing dipalmitoyl-PC synthesis by acyl remodeling, and adipose triglyceride lipase, considered as responsible for fatty acid supply for surfactant PC synthesis, were elevated. These results, together with a considerable body of other confirmative evidence, suggest that rhKGF should be developed into a therapeutic option to treat preterm infants at risk for impaired lung development.     

Differentially Expressed miRNAs Influence Metabolic Processes in Pituitary Oncocytoma

Neurochemical Research - Spindle cell oncocytomas (SCO) of the pituitary are rare tumors accounting for 0.1–0.4% of all sellar tumors. Due to their rarity, little information is available...     

Novel,X-ray supported kinetic imaging of hidden-lifestyle arthropods

Dear Editor,There are several arthropods,which live and develop covertly in plant tissues.The plant tissues surrounding them provide them with shelter during their vulnerable developing stage or ensure overwintering as well as they can supply them with essential food for their ontogenetic development(McNaughton,1983).     

Blood flow of the right and left submandibular gland during unilateral carotid artery occlusion in rat: role of nitric oxide

The aim of the present study was to investigate the effect of unilateral carotid artery occlusion on the blood flow of submandibular gland in anesthetized rats and identify the role of nitric oxide (NO) in blood flow changes after the artery occlusion. L-NAME (N omega-nitro-L-arginine-methyl-ester; 10 mg/kg/day, per os) dissolved in tap water was used to block nitric oxide synthase. Glandular blood flow was measured using Sapirstein's indicator (86Rb) distribution technique. In the control animals the blood flow of left (ligated side) submandibular gland was lower than in the right (unligated side) one (right: 76.4+/-15.4 ml/min/100 g, 64.1+/-13.4 ml/min/100 g, p<0.01). The blood flow of submandibular glands decreased in NOS blocked group versus control. The vascular resistance after L-NAME treatment was elevated (control: 11+/-2.3 R/kg, L-NAME: 17.5+/-4.1 R/kg, p<0.001). In L-NAME group the difference between blood flow value of the left and right submandibular gland was significantly lower than in the control group (control: -16%, NAME: -8%, p<0.01). Conclusion: The maintenance of the blood flow in the left submandibular gland during ligation of the left common carotid artery could be due to the good vascular anastomotic system at these regions and adaptation of the submandibular vessels to the decreased perfusion pressure. Nitric oxide may have a role in the regulation of blood flow tinder this condition.     

Structure and dynamics of thioguanine-modified duplex DNA

Mercaptopurine and thioguanine, two of the most widely used antileukemic agents, exert their cytotoxic, therapeutic effects by being incorporated into DNA as deoxy-6-thioguanosine. However, the molecular mechanism(s) by which incorporation of these thiopurines into DNA translates into cytotoxicity is unknown. The solution structure of thioguanine-modified duplex DNA presented here shows that the effects of the modification on DNA structure were subtle and localized to the modified base pair. Specifically, thioguanine existed in the keto form, formed weakened Watson-Crick hydrogen bonds with cytosine and caused a modest approximately 10 degrees opening of the modified base pair toward the major groove. In contrast, thioguanine significantly altered base pair dynamics, causing an approximately 80-fold decrease in the base pair lifetime with cytosine compared with normal guanine. This perturbation was consistent with the approximately 6 degrees C decrease in DNA melting temperature of the modified oligonucleotide, the 1.13 ppm upfield shift of the thioguanine imino proton resonance, and the large increase in the exchange rate of the thioguanine imino proton with water. Our studies provide new mechanistic insight into the effects of thioguanine incorporation into DNA at the level of DNA structure and dynamics, provide explanations for the effects of thioguanine incorporation on the activity of DNA-processing enzymes, and provide a molecular basis for the specific recognition of thioguanine-substituted sites by proteins. These combined effects likely cooperate to produce the cellular responses that underlie the therapeutic effects of thiopurines.     

Unidirectional shift in leaf morphology of coexisting species — a possible indicator of palaeoclimatic differences

The pre-Neogene basement of the Pannonian domain is built up by a collage of terranes deriving from different parts of the Tethys, which finally accreted in the Late Oligocene–Early Miocene times. Combined stratigraphical, sedimentological, palaeomagnetic and tectonic investigations have revealed the palaeogeographic position of the Palaeogene Basin, including the Buda and Bükk tectonic units However, despite floristic similarities, the Buda and Bükk regions also show important physiognomic differences. In the vicinity of Budapest (Buda unit), the large size and width of leaves are conspicuous, whereas in Eger-Kiseged (Bükk unit), leaves are definitely smaller and narrower. In order to define the differences quantitatively, morphometrical measurements were adopted. The shape and size of leaf fossils were compared by means of a circular grid (Hill, 1980). Leaves of 4 dominant species (Sloanea elliptica (Andreánszky) Z. Kva?ek & Hably, Engelhardia orsbergensis (Wessel & Weber) Jähnichen, Mai & Walther, Eotrigonobalanus furcinervis (Rossmässler) Walther & Kva?ek, and Zizyphus zizyphoides (Unger) Weyland were the target of our study. The average leaf area is 1.4–2.3 times larger in the Buda tectonic unit (Budapest locality) than in the Bükk tectonic unit (Eger-Kiseged locality). Statistical tests proved highly significant differences between these values. Regarding the asymmetry of the leaf lamina, the four species differed considerably. Nevertheless, a significant difference between the two localities was shown only in one of them (Sloanea elliptica). Consequently, a significant alteration of measures of asymmetry as a function of habitat conditions was not indicated. Smaller leaf area and significantly narrower leaf blade are possible indicators of drier climatic conditions in the Bükk unit.     

Changes in flux pattern of the central carbohydrate metabolism during kernel development in maize

Developing kernels of the inbred maize line W22 were grown in sterile culture and supplied with a mixture of [U-13C6]glucose and unlabeled glucose during three consecutive intervals (11-18, 18-25, or 25-32 days after pollination) within the linear phase of starch formation. At the end of each labeling period, glucose was prepared from starch and analyzed by 13C isotope ratio mass spectrometry and high-resolution (13)C NMR spectroscopy. The abundances of individual glucose isotopologs were calculated by computational deconvolution of the NMR data. [1,2-(13)C2]-, [5,6-(13)C2]-, [2,3-(13)C2]-, [4,5-(13)C2]-, [1,2,3-(13)C3]-, [4,5,6-(13)C3]-, [3,4,5,6-(13)C4]-, and [U-(13)C6]-isotopologs were detected as the major multiple-labeled glucose species, albeit at different normalized abundances in the three intervals. Relative flux contributions by five different pathways in the primary carbohydrate metabolism were determined by computational simulation of the isotopolog space of glucose. The relative fractions of some of these processes in the overall glucose cycling changed significantly during maize kernel development. The simulation showed that cycling via the non-oxidative pentose phosphate pathway was lowest during the middle interval of the experiment. The observed flux pattern could by explained by a low demand for amino acid precursors recruited from the pentose phosphate pathway during the middle interval of kernel development.