P2Y₂ receptor activation decreases blood pressure and increases renal Na⁺ excretion

ATP and UTP are endogenous agonists of P2Y(2/4) receptors. To define the in vivo effects of P2Y(2) receptor activation on blood pressure and urinary excretion, we compared the response to INS45973, a P2Y(2/4) receptor agonist and UTP analog, in wild-type (WT) and P2Y(2) receptor knockout (P2Y(2)-/-) mice. INS45973 was administered intravenously as a bolus injection or continuous infusion to determine effects on blood pressure and renal function, respectively. Within seconds, bolus application of INS45973 (0.1 to 3 mg/kg body wt) dose-dependently decreased blood pressure in WT (maximum response -35 ± 2 mmHg) and to a similar extent in endothelial nitric oxide synthase knockout mice. By contrast, blood pressure increased in P2Y(2)-/- (maximum response +18 ± 1 mmHg) but returned to basal levels within 60 s. Continuous infusion of INS45973 (25 to 750 μg·min(-1)·kg(-1) body wt) dose-dependently increased urinary excretion of Na(+) in WT (maximum response +46 ± 15%) but reduced Na(+) excretion in P2Y(2)-/- (maximum responses of -45 ± 15%) mice. In renal clearance experiments, INS45973 did not affect glomerular filtration rate but lowered blood pressure and increased fractional excretion of fluid, Na(+), and K(+) in WT relative to P2Y(2)-/- mice. The blood pressure responses to INS45973 are consistent with P2Y(2) receptor-mediated NO-independent vasodilation and implicate responses to endothelium-derived hyperpolarizing factor, and P2Y(2) receptor-independent vasoconstriction, probably via activation of P2Y(4) receptors on smooth muscle. Systemic activation of P2Y(2) receptors thus lowers blood pressure and inhibits renal Na(+) reabsorption, effects suggesting the potential utility of P2Y(2) agonism in the treatment of hypertension.     

Recovery of photosynthetic capacity in <Emphasis Type=Italic>Vaccinium vitis</Emphasis>-<Emphasis Type=Italic>idaea</Emphasis> during mild spells in winter

Recent studies suggest that evergreen plants may maintain their photosynthetic capacity through the winter. Since mild winters are predicted to be more frequent in the future, the metabolic activity of plants is also likely to increase. The aim of the present study was to assess how various environmental factors, such as temperature, photoperiod and preceding frost, affect the recovery of photosynthesis during a mild spell in winter. The recovery of photosynthesis was studied in a series of growth chamber experiments where the overwintering of lingonberry (Vaccinium vitis-idaea) was interrupted by an intermittent warm spell of 1 week during different phases of winter. Rapid activation was observed in all the experiments during the first 3–4 days. No obvious effects of the phase of winter or photoperiod on the recovery of photosynthesis were observed, but a severe freezing treatment prior to the warm spell retarded the recovery significantly. Once recovered, however, lingonberry was able to maintain high rates of photosynthesis even at near-freezing temperatures, which prevail in their natural sub-nivean environment. The apparent quantum yield of photosynthesis remained high through the winter for lingonberry. This may prove advantageous for evergreen dwarf shrubs which overwinter in dim environments under snow.     

Synthesis, 18F-labeling, and in vitro and in vivo studies of bombesin peptides modified with silicon-based building blocks

The gastrin-releasing peptide receptor (GRPr) is overexpressed on various human tumors. The goal of our study was the synthesis of new 18F-labeled bombesin analogues for the PET imaging of GRPr expression in prostate tumor using a silicon-based one-step n. c. a. radiolabeling method. The silicon-containing building blocks were efficiently coupled to the N-terminus of the peptides via solid-phase synthesis. Radiolabeling of the obtained peptide precursors proceeded smoothly under acidic conditions (34-85% conversion). Using the di-tert-butyl silyl building block as labeling moiety, products containing a hydrolytically stable 18F-label were obtained. In in vitro receptor binding experiments 2-(4-(di-tert-butylfluorosilyl)phenyl)acetyl-Arg-Ava-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH 2 ( 4b, IC50 = 22.9 nM) displayed a 12-fold higher binding affinity than 2-(4-(di-tert-butylfluorosilyl)phenyl)acetyl-Arg-Ava-Gln-Trp-Ala-Val-Gly-His(3Me)-Sta-Leu-NH2 ( 3b, IC50 = 276.6 nM), and 4b was therefore chosen for further evaluation. In vitro and ex vivo metabolite studies of [18F]4b showed no significant degradation. In biodistribution experiments, tumor uptake of [18F]4b was low and unspecific, whereas the GRPr-rich pancreas revealed a high and specific accumulation of the radiotracer. This study demonstrates the applicability of our silicon-based one-step n. c. a. radiolabeling method for the synthesis of new 18F-labeled bombesin derivatives. This innovative approach represents a general, straightforward access to radiolabeled peptides as PET imaging probes.     

Diatoms: unicellular surrogates for macroalgal community structure in streams?

As wholesale biodiversity assessment is often impractical, the use of surrogates that reflect the assemblage structure and diversity of other taxa has attracted increased attention. We sampled 47 boreal streams for diatoms and macroalgae and examined their assemblage patterns along major environmental gradients. Our main intention was to examine whether diatoms might be useful surrogates for macroalgae in boreal streams. We also assessed whether taxon richness and community composition provided similar insights into the patterns of cross-taxon concordance. According to canonical correspondence analysis, diatom distribution was most strongly related to water pH, conductivity, latitude and longitude, and macroalgal distribution to water pH and iron content, latitude and bed instability. In Mantel’s test, diatoms and macroalgae showed significant cross-taxon concordance. However, there was no significant correlation between taxon richness of the two algal groups, likely reflecting their differing responses to environmental variables. We found evidence that although diatoms and macroalgae are partly controlled by different environmental factors, they are segregated rather similarly along latitude and a few environmental gradients such as water pH and iron content. We conclude that, at least at broad geographical extents and in small streams, diatoms reflect the structure of the macroalgal community and are therefore useful surrogates for cost-effective biomonitoring of algal communities in streams.     

Season of Birth and Lung Fibrosis among Workers Exposed to Asbestos

The season of birth has been suggested to influence the development of some diseases, but its role in lung fibrosis seems to not have been studied previously. The aim of this study was to investigate the relation between the season of birth and fibrotic abnormalities as detected radiologically in high‐resolution computed tomography (HRCT) among workers exposed to asbestos. The HRCT examination was performed on 528 study subjects. Multiple ordinal regression analysis adjusting for covariates was used to study the relations between birth month or season and radiological fibrosis signs. Subjects born in autumn or winter had more extensive fibrotic changes than those born in spring or summer. This applied to all fibrotic changes, apart from subpleural nodules, but only the overall fibrosis score, septal lines, and honeycombing showed statistically significantly higher values in comparison to spring births. The highest scores were detected among those born in autumn and winter months (September–February). These results suggest that there are differences in fibrotic radiological abnormalities according to the season of birth in adults exposed to asbestos. Several hypotheses could explain the observed findings, including the effects of early respiratory infections, cold temperature, and differences in air pollution levels, as well as some metabolic and hormonal effects.     

Rapid genetic analysis in congenital hyperinsulinism

BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.     

The Effect of Ethionine Feeding on the Retention of A Single Per Os Dose of Methyl Mercury on Rat

Six adult female rats were daily fed a diet containing DL-ethionine during three weeks. One daily rat dose was 30 mg of ethionine. Six similar rats, the controls, were kept on the same diet without ethionine. On the 21st day of the experiment all rats were given one dose of 203Hg labeled methyl mercury by stomach tube. Each rat received 163 µg in terms of metallic mercury. Ninety hrs. after the mercury administration all rats were sacrificed and the mercury contents of the brains, livers, caudal femoral muscles, erythrocytes and blood plasma were determined. The mean plasma mercury content was significantly (P<0.01) greater in the ethionine fed rats when compared to the controls.