Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696]

Background

Stent length serves as a predictor of restenosis in use of bare metal stents (BMS). This has been demonstrated in a feasibility study that used a single short BMS implant (<9 mm) in a high proportion of lesions; the study observed a low rate of restenosis.

Methods

We performed a pilot prospective study to investigate in a series of consecutive patients the immediate and long-term effects of implantation of either 1) a single short BMS for all lesions with low probability of restenosis or 2) a drug-eluting stent (DES) for all other lesions.

Results

The 200 patients studied had 236 coronary artery lesions that were treated with short BMS in 168/236 patients (71.2%) and with DES in 68/236 patients (28.8%). Angiographic success was achieved in 230/236 lesions (97.5%) and procedural success in 194/200 patients (97.0%). Restenosis occurred in 15/153 lesions (9.8%) after short BMS, in 3/62 lesions (4.8%) after DES, and in 18/215 of all lesions (8.4%) angiographically controlled after six to eight months. Target vessel revascularization was performed in 16/218 lesion (7.4%).

Conclusion

Most of the coronary artery lesions in this small group of consecutive patients were treated sufficiently with a single BMS implant. This differential approach of treating suitable lesions in medium- to large-sized vessels with a single short BMS device and treating all other lesions with a DES implant resulted in a low incidence of restenosis.     

Early vegetation succession on gravel bars of Czech Carpathian streams

Rivers with a natural flooding regime and gravel accumulations are an important natural habitat endangered by regulations and other types of human impact. Succession after disturbances by floods creates a mosaic of different vegetation types, some of them containing rare specialist species. We studied vegetation succession and changes in plant diversity on river gravel bars of four streams in the Western Carpathians and their foothills in the eastern Czech Republic. This area experienced extreme 50-year flood event in May 2010. Gravel bar vegetation was destroyed, some of the former bars were covered by sediments, and some new bars arose. We sampled gravel bar vegetation two months after the floods and repeated the sampling on each site during the next three years. Initial vegetation has developed through a sparse and species-rich stage into denser stands with more shade-tolerant species. In the fourth year, tall herbs, such as Urtica dioica, Phalaris arundinacea and the alien Impatiens glandulifera, dominated the communities, but shrub vegetation started to develop only in a few places. Species capable of vegetative dispersal prevailed over species dispersed by seeds only. Altitude and size of gravel/stone particles were identified as important factors affecting vegetation succession. The succession ran faster on gravelly substrates at lower altitudes than on stony substrates at higher altitudes. Although the studied streams are partly influenced by human interventions and host only few gravel bar specialists, they are of considerable conservation importance.     

Serum creatine is not a reliable marker of muscular fitness in young adults

Purpose: Elevated serum creatine and higher handgrip strength are individually associated with better health profiles yet the link between two variables remains unknown. In this cross-sectional study, we evaluated serum creatine levels in relation to handgrip strength in a cohort of 130 young healthy adults (61 women and 69 men; age 23.3?±?2.6?years), while controlling for age, gender, fat-free mass and biomarkers of creatine metabolism as effect modifiers.

Materials and methods: Serum creatine, creatinine and guanidinoacetic acid (GAA) levels were measured with liquid chromatography-tandem mass spectroscopy, while handgrip strength was assessed with a hydraulic hand dynamometer.

Results: Hierarchical multiple regression revealed that our model as a whole explained 79.9% of the variance in handgrip strength (p?p?p?>?0.05).

Conclusions: Having higher blood creatine appears to be unrelated with better physical performance in young healthy adults. Serum creatine was not a reliable marker of muscular fitness in this population.     

Microtopography‐induced transient waterlogging affects switchgrass (Alamo) growth in the lower coastal plain of North Carolina,USA

Very limited information is currently available on growth responses of switchgrass (lowland cultivars) to transient waterlogging in lowland or poorly drained areas. This study investigated impacts of microtopography‐induced transient waterlogging on switchgrass (Alamo cultivar) growth, represented by leaf‐level gas exchange and biomass yield, in an established experimental field located in the Atlantic coastal plain of North Carolina, USA. Intensive leaf‐level gas exchange measurements were conducted on switchgrass at paired spots with distinct elevations in three sub‐blocks. Aboveground biomass was randomly collected across the study field to explore the potential impacts of the transient waterlogging on biomass yield. The sum of excess water (SEW) was calculated based on measured instantaneous water table depth to generalize the relationship between biomass yield and intensity of transient waterlogging. Results showed significant (P ≤ 0.0001) treatment effects on leaf‐level gas exchange, characterized by evident reduction in both CO₂ assimilation rate and stomatal conductance when water table was at or near the soil surface at low positions. Negative impacts of transient waterlogging on leaf‐level gas exchange became more evident with the increasing of elevation differences between paired subplots. Stomatal closure was found to be the main mechanism responsible for the decline of net assimilation under transient waterlogging. Aboveground biomass yields of switchgrass showed relatively high spatial variability and were positively and linearly correlated with microtopography (represented by elevation in the analysis) (P < 0.03, R² > 0.77). Further analysis showed that biomass yields were negatively correlated with SEW (P < 0.001, R² > 0.6) with an exponential relationship. Results of this study strongly demonstrated transient waterlogging could negatively affect switchgrass growth by suppressing leaf‐level gas exchange rates and ultimately reducing biomass yield. Findings from this study have critical implications for evaluating the economic viability of growing switchgrass on marginal lands that are subject to transient waterlogging stresses.     

The secretory cells of the submaxillary gland in the perinatal period of development in the rat

Summary Secretory cell differentiation in the submaxillary gland of the rat was investigated electron microscopically within the period of the 19th–22nd embryonic and the 1st–6th postnatal days.Within this period three types of secretory cells were identified which differed mainly in the morphological appearance of their secretory granules. In addition to the previously described cells of the terminal tubules and the glandular cells of the acini, we observed secretory cells with polymorphic granules, characterized by the presence of small osmiophilic bodies in the matrix of the granules, both after simple and double fixation. The chronological occurrence as well as the quantitative representation of these three types of secretory cells changes in the course of the period investigated. The cells of the terminal tubules are differentiated at the 19th embryonic day; the secretory cells with polymorphic granules by the 21st embryonic day; the glandular cells of the acini do not appear until after birth. It is presumed that the cells of the terminal tubules are precursors of the glandular cells of the acini and that the cells containing polymorphic granules represent an intermediate stage between them.

---

Zusammenfassung Die Differenzierung der Drüsenzellen der Glandula submaxillaris bei Ratten in der Periode vom 19.–22. Tage pränatal und vom 1.–6. Tage postnatal wurde elektronenmikroskopisch studiert.In dieser Periode haben wir in dieser Drüse drei Typen von sezernierenden Zellen festgestellt, welche sich morphologisch hauptsächlich bezüglich verschiedenartiger Sekretionsgranula voneinander unterscheiden. Zu den schon früher beschriebenen Zellen der terminalen Tubuli und den Drüsenzellen der Azini haben wir neu die sezernierenden Zellen mit polymorphen Granula, welche sich durch das Vorhandensein osmiophiler Körperchen in der Matrix der Granula nach einfacher sowohl als auch zweifacher Fixation auszeichnen, angereiht. Das zeitliche Erscheinen und die quantitative Verteilung der erwähnten drei Typen von Sekretionszellen änderten sich während der Beobachtungsperiode dahin, daß die Zellen der terminalen Tubuli am 19. Tage, die Sekretionszellen mit polymorphen Granula am 21. Tage der pränatalen Periode sich differenzieren und die Drüsenzellen der Azini erst nach der Geburt erscheinen.Unserer Ansicht nach sind die Zellen der terminalen Tubuli die Mutterzellen der Drüsenzellen der Azini und die sezernierenden Zellen mit polymorphen Granula das Übergangsstadium zwischen ihnen beiden.

     

Glucobrassicin a potential inhibitor of unusual type affecting the Germination and growth of plants; mechanism of its action

A water-soluble germination- and growth-inhibitor present in plants of Brassica genus was studied. Aqueous eluates from chromatograms of methanolic extracts of Savoy cabbage, cabbage and Brussels’ sprouts leaves, and of Brussels’ sprouts roots, inhibited the growth of wheat; the chromatographic behaviour of this inhibitor was similar to that of the thioglycoside glucobrassicin (GLUBR). GLUBRat 10^-3 m, and the supposed product of its enzymatic degradation, 3-indolylacetonitrile (IAN) at 10^-4 m, inhibited the growth of wheat and clover in a similar manner. At lower concentrations, both substances gradually enhanced growth. In contrast to IAN, GLUBR did not appreciably influence the growth of Savoy cabbage. Other products of GLUBR degradation, such as thiocyanate ion and ascorbigen, influenced the growth to a lesser extent and in a different way. At higher concentrations GLUBR and IAN also inhibited the germination of clover seeds. The biological effect of GLUBR is dependent on the presence of the indole nucleus in its molecule; the thioglycoside glucoiberin, which is not of indolic character, does not influence growth. The presence of free myrosinase was shown in intact wheat seedlings. Hence, GLUBR taken in by the germinating plants must undergo enzymatic cleavage. The in vitro activity of myrosinase in wheat and clover was lower than in Savoy cabbage, but the quantity of IAN formed at a pH corresponding to the natural pH was higher in wheat and clover than in Savoy cabbage, where the formation of the growth-inactive ascorbigen prevailed. On the basis of these results the hypothesis was formulated that GLUBR, the indolic complex from the generaBrassica, Raphanus, Cochleria, Nasturtium, Barbarea andSisymbrium, is a representative of a class of potential inhibitors of growth and germination, whose activity can be explained by the liberation of large amounts of growth-affecting substances during their specific enzymatic cleavage.     

Consumption of NADPH for 2-HG Synthesis Increases Pentose Phosphate Pathway Flux and Sensitizes Cells to Oxidative Stress

1. Download high-res image (163KB)
2. Download full-size image

     

Possible association of the allele status of the CS.7/HhaI polymorphism 5′ of the CFTR gene with postnatal female survival

Cystic fibrosis (CF) patients show a high degree of linkage disequilibrium between the CF transmembrane conductance regulator (CFTR) gene and polymorphisms 5′ of that gene. To determine whether the region 5′ of CFTR contains biologically important sequences, the allele frequencies of six CFTR-linked polymorphisms (metH/MspI, XV-2c/TaqI, CS.7/HhaI, KM19/PstI, MP6-d9/MspI, J44/XbaI) were determined in 417 randomly selected elderly individuals (over 75 years of age) from the Czech population. The elderly individuals were considered “escapees” of strong selective pressures that had operated during their lifetime, prior to the introduction of modern health care since 1950. The pooled allele frequencies of the analyzed marker polymorphisms in the elderly did not significantly differ from published data. However, when analyzed by sex, the allele frequencies of markers CS.7/HhaI and KM19/PstI differed significantly (P < 0.05) between elderly females and males. The allele frequencies of the six polymorphisms were then determined in 646 newborns and 345 young adults of reproductive age; these individuals were selected in a similar manner and drawn from the same population. In these control groups, the studied marker polymorphisms exhibited no statistically significant differences between sexes and/or between individuals of the same sex, only between different age groups. A gradual relative increase in the frequency of allele “2” of marker CS.7/HhaI was observed from newborn females to elderly women, the overall difference in allele frequencies of this marker polymorphism between newborn females and elderly women reaching statistical significance (P < 0.05). Interestingly, allele “2” is the major constituent of the extended “B-haplotype”, which is in strong linkage disequilibrium with common CF alleles. Taken together, our data suggest that the region spanning markers CS.7 and KM19 is associated with a genetic factor that influences postnatal female survival, providing a possible mechanism for increasing the frequency of particular mutations in the adjacent CFTR gene. Received: 30 January 1996 / Revised: 16 December 1996     

Chronic Blockade of Nitric Oxide Synthesis Elevates Plasma Levels of Catecholamines and Their Metabolites at Rest and During Stress in Rats

Formation of nitric oxide, an endothelium-derived relaxing factor, can be inhibited by administration of N-nitro-L-arginine methylesther (L-NAME). In the present study, the activity of the sympathoadrenal system in rats with blood pressure (BP) elevation induced by L-NAME was investigated. L-NAME was administered in a dose of 50 mg/kg, i.p. every 12 h for 4 days. Blood samples were collected via chronically inserted arterial catheters in conscious, freely moving rats at rest and during immobilization stress. Plasma epinephrine (EPI), norepinephrine (NE), and dopamine (DA), as well as catecholamine metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were measured by HPLC method. In L-NAME treated animals, which showed a significant increase in BP, plasma EPI levels were markedly elevated both before and during stress. Plasma NE levels were not significantly increased, however, DHPG levels, which indicate NE turnover and reuptake, were highly elevated. Plasma DA levels were not changed after L-NAME administration but DA metabolite DOPAC showed a significant elevation both under basal conditions and during stress. Thus, the present results indicate that the prolonged blockade of nitric oxide synthesis that causes arterial hypertension is associated with an activation of the sympathoadrenal system.     

NTRS, a new family of highly repetitive DNAs specific for the T1 chromosome of tobacco

Species-specific repeated DNAs are important for identifying genomic components of hybrid organisms in plant breeding and in taxonomic studies, and we have previously described the HRS60 and GRS families of highly repetitive DNA sequences in tobacco. Here we describe a new family of highly repetitive DNA sequences termed NTRS (SspI family) that we have isolated from Nicotiana tomentosiformis (Goodspeed) and characterized and that is specific for the genomes of several species of the subgenus Tabacum. In situ hybridization showed that NTRS sequences are present in three pairs of chromosomes of N. tomentosiformis, six pairs of chromosomes of N. kawakamii, and only one pair of chromosomes of N. tabacum at an intercalary site. The NTRS family is not present in the N. otophora genome. The majority of NTRS sequences appeared to be organized in tandem arrays in which local DNA structures sensitive to single strand-specific chemical probes, potassium permanganate, and osmium tetroxide complexed with pyridine revealed a periodicity of 220 bp, equal to the length of the repeat unit. The inner cytosine in CCGG and CC(A/T)GG sequences of the NTRS family is frequently methylated. Cloned and sequenced NTRS monomeric units are 212–219 bp in length and show 83.5%–95% mutual homology. They exhibit properties characteristic for molecules that possess stable intrinsic curvature, but there are differences among individual monomers in the degree of curvature. NTRS sequences like HRS60 and GRS sequences, were found to specify nucleosome positions. Received: 12 November 1996 / in revised form: 12 May 1997 / Accepted: 12 May 1997