Effect of ethanol and acetaldehyde at clinically relevant concentrations on atrial inward rectifier potassium current IK1: separate and combined effect.

Atrial fibrillation is the most common arrhythmia at alcohol consumption. Its pathogenesis is complex, at least partly related to changes of cardiac inward rectifier potassium currents including IK1. Both ethanol and acetaldehyde have been demonstrated to considerably modify IK1 in rat ventricular myocytes. However, analogical data on the atrial IK1 are lacking. The present study aimed to analyse IK1 changes induced by ethanol and acetyldehyde in atrial myocytes. The experiments were performed by the whole cell patch-clamp technique at 23 ± 1°C on enzymatically isolated rat and guinea-pig atrial myocytes as well as on expressed human Kir2.3 channels. Ethanol (8 - 80 mM) caused a dual effect on the atrial IK1 showing the steady-state activation in some cells but inhibition in others in agreement with the ventricular data; on average, the activation was observed (at 20 mM by 4.3 and 4.5% in rat and guinea-pig atrial myocytes, respectively). The effect slightly increased with depolarization above -60 mV. In contrast, the current through human Kir2.3 channels (prevailing atrial IK1 subunit) was inhibited in all measured cells. Unlike ethanol, acetaldehyde (3 µM) markedly inhibited the rat atrial IK1 (by 15.1%) in a voltage-independent manner, comparably to the rat ventricular IK1. The concurrent application of ethanol (20 mM) and acetaldehyde (3 µM) resulted in the steady-state IK1 activation by 2.1% on average. We conclude that ethanol and even more acetaldehyde affected IK1 at clinically relevant concentrations if applied separately. Their combined effect did not significantly differ from the effect of ethanol alone.

Investigation of sanguinarine and chelerythrine effects on LPS-induced inflammatory gene expression in THP-1 cell line.

Quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine have been used in folk medicine for their wide range of useful properties. One of their major effect is also anti-inflammatory activity, that is not clarified in detail. This study focused on the ability of these alkaloids to modulate the gene expression of pro-inflammatory tumour necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1, also known as CCL-2), interleukin (IL)-6, IL-1ß and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and IL-10. The effect of these alkaloids was compared with that of conventional drug prednisone. Human monocyte-derived macrophages were pre-treated with alkaloids or prednisone and inflammatory reaction was induced by lipopolysaccharide. Changes of gene expression at the transcriptional level of mentioned cytokines were measured. In our study mainly affected pro-inflammatory cytokines were CCL-2 and IL-6. Two hours after LPS stimulation, cells influenced by sanguinarine and chelerythrine significantly declined the CCL-2 expression by a factors of 3.5 (p<0.001) and 1.9 (p<0.01); for those treated with prednisone the factor was 5.3 (p<0.001). Eight hours after LPS induction, both alkaloids significantly diminished the CCL-2 expression. The lower expression was found for sanguinarine--lower by a factor of 4.3 than for cells treated with the vehicle (p<0.001). Two hours after LPS stimulation, cells treated with sanguinarine decreased the IL-6 mRNA level by a factor of 3.9 (p<0.001) compared with cells treated with the vehicle. Chelerythrine decreased the level of IL-6 mRNA by a factor of 1.6 (p<0.001). Sanguinarine decreased gene expression of CCL-2 and IL-6 more than chelerythrine and its effect was quite similar to prednisone. Four hours after LPS stimulation, cells pre-treated with sanguinarine exhibited significantly higher expression (a factor of 1.7, p<0.001) of IL-1RA than cells without sanguinarine treatment. Our results help to clarify possible mechanisms of action of these alkaloids in the course of inflammation.

Effect of diplacone on LPS-induced inflammatory gene expression in macrophages.

Flavonoids are commonly studied for their anti-inflammatory effects; however, this is the first paper describing the possible antiphlogistic activity of a geranylated flavanone. This study focused on the ability of diplacone to modulate the gene expression of pro-inflammatory tumour necrosis factor alpha and monocyte chemoattractant protein 1, and of anti-inflammatory zinc finger protein 36. The action of diplacone was also compared with that of conventional drug indomethacin. Human monocyte-derived macrophages of the human monocytic leukaemia cell line were pretreated with diplacone or indomethacin. Subsequently, inflammatory reaction was induced by lipopolysaccharide, and changes of tumour necrosis factor alpha, monocyte chemoattractant protein 1 and zinc finger protein 36 gene expression at the transcriptional level were measured. In this model, diplacone significantly down-regulated the expression of tumour necrosis factor alpha and monocyte chemoattractant protein 1 and up-regulated the zinc finger protein 36 expression. This makes diplacone a promising molecule for treatment of the inflammatory stage of diseases. The effect of diplacone in decreasing lipopolysaccharide-induced inflammatory gene expression is in many ways similar to that of the conventional drug indomethacin.

Monitoring of persistent organic pollutants in Africa. Part 2: design of a network to monitor the continental and intercontinental background.

A network for the study of long-term trends of the continental background in Africa and the intercontinental background of persistent organic pollutants as resulting from long-range transport of contaminants from European, South Asian, and other potential source regions, as well as by watching supposedly pristine regions, i.e. the Southern Ocean and Antarctica is designed. The results of a pilot phase sampling programme in 2008 and meteorological and climatological information from the period 1961-2007 was used to apply objective criteria for the selection of stations for the monitoring network: out the original 26 stations six have been rejected because of suggested strong local sources of POPs and three others because of local meteorological effects, which may prevent part of the time long-range transported air to reach the sampling site. Representativeness of the meteorological patterns during the pilot phase with respect to climatology was assessed by comparison of the more local airflow situation as given by climatological vs. observed wind roses and by comparison of backward trajectories with the climatological wind (NCEP/NCAR re-analyses). With minor exceptions advection to nine inspected stations was typical for present-day climate during the pilot phase, 2008. Six to nine stations would cover satisfyingly large and densely populated regions of North-eastern, West and East Africa and its neighbouring seas, the Mediterranean, Northern and Equatorial Atlantic Ocean, the Western Indian Ocean and the Southern Ocean. Among the more densely populated areas Southern Cameroon, parts of the Abessinian plateau and most of the Great Lakes area would not be covered. The potential of the network is not hampered by on-going long-term changes of the advection to the selected stations, as these do hardly affect the coverage of target areas.

[Gene expression changes during insulin resistance and "diabesity" in insulin-sensitive tissues and possibilities of their regulation]. / Zmeny v genové expresi behem inzulínové rezistence a "diabezity" v inzulín-senzitivnich tkáiních a moznosti jejich regulace.

Type 2 diabetes mellitus (T2DM) gains considerable and pandemic proportions and becomes noticeable problem in a social and economic sphere. In spite of all effort, exact mechanism of T2DM origin has not been elucidated yet. Studying of transcriptom is one possibility how to explain pathophysiological processes in insulin-sensitive tissues. Obtained data can serve as a base for predicting of new therapeutic targets of this disease. This overall review introduces crucial genes whose level of products changes during T2DM. The article gives notice to a diet composition, which is an important environmental factor, which is able to influence a disease outbreak. Not only the role of fats, but also influence of some plant compounds, which would be able to serve as an alternative to present prophylaxis or treatment of T2DM, have been discussed.

Frequency of representative single nucleotide polymorphisms associated with inflammatory bowel disease in the Czech Republic and Slovak Republic.

Involvement of genetic factors in the aetiology of inflammatory bowel disease (IBD) has been known for a long time. Our aim was to investigate the prevalence of polymorphisms in NOD2, ICAM-1 and CCR5 genes in Czech and Slovak patients with IBD in comparison with healthy controls. The frequency of well-known mutations (R702W, G908W and 1007fs in the NOD2 gene; K469E in the ICAM-1 gene, and Delta32 in the CCR5 gene) involved in IBD was tested in 45 patients with CD and 22 patients with UC. The allele frequency of these mutations was determined and genotype-phenotype correlation was specified. Isolated DNA was genotyped, and allele frequency was counted and statistically verified. Significant differences between the healthy control group and CD patients were observed in mutation 1007fs of the NOD2 gene (P = 0.0203). We also associated allele E469 of the ICAM-1 gene with CD (P = 0.0024). No significant association between other alleles and CD was found, and no gene variation was linked to UC. The number of mutations and mutated genes was higher among patients with CD than among patients with UC. Our results support previous findings about participation of mutations of NOD2 and ICAM-1 genes in IBD. We confirmed that both CD and UC are polygenic diseases with a genedosage effect. This observation strengthens the opinion that genetic factors play a more important role in CD than in UC.

[The Rubinstein-Taybi syndrome or a broad thumb-hallux syndrome]. / Rubinstein-Taybi syndrom nebo-li syndrom sirokých palcu.

The Rubinstein-Taybi syndrome (broad thumb-hallux syndrome) is a rare congenital disease with prevalence 1:125,000 of life-born children. It is characterised by multiplex malformations, which includes growth and psychomotor retardation. Up to this date, over 1000 cases have been described in literature. This review is mainly focused on a description of symptoms, which occur in the syndrome mentioned above and serve as main diagnostic markers. Mutations in the CBP and the p300 genes have been associated with this disease as well. Therefore, substantial part is devoted to aetiology, where emphasis is put on a genetic origin of the Rubinstein-Taybi syndrome. Possibilities of this diagnose are mentioned at the end of the article.

Demonstration of acid phosphatase in Eimeria spp.: partial characterization of the enzyme in E. vermiformis.

Sporozoite extracts of E. vermiformis, E. stiedai, and E. tenella are rich in acid phosphatase activity. They contain specific enzyme activities equal to or greater than those reported for other highly virulent protozoan parasites. The absolute amount of enzyme activity per oocyst dramatically increases during sporulation of E. stiedai and E. vermiformis. Partial characterization of the acid phosphatase activity of E. vermiformis indicates that sporozoites account for greater than 92% of the total activity in sporulated oocysts, that the enzyme is resistant to inhibition by tartrate, and that it can be separated into two forms by anion exchange chromatography.

Improved method for high-yield excystation and purification of infective sporozoites of Eimeria spp.

This report describes a new, gentle procedure for rapid and efficient excystation of large numbers of infective sporozoites of Eimeria vermiformis and Eimeria stiedai. Excysted sporozoites are purified using modifications of a previously described ion-exchange chromatography method. The procedure avoids physical breakage of oocysts and results in greater than 70% recovery of the sporozoites present as sporulated oocysts (i.e. 5-6 sporozoites per sporulated oocyst). The recovered sporozoites are greater than 95% pure and are infective in vivo. We routinely isolate greater than 2 x 10(8) sporozoites without the use of specialized or expensive equipment.

Teaching and hospital costs: the case of radiology.

Investigates production and cost effects of teaching in radiology departments. If students are substitutes for physicians, production costs may be less in teaching than in non-teaching hospitals for a given level of output. Empirical results for Veterans Administration hospitals suggest that teaching reduces costs for most radiology procedures. If teaching can reduce costs of primary products, teaching hospitals may be able to provide a given program of patient care at lower costs than non-teaching hospitals. However, costs might still be higher at teaching hospitals than non-teaching hospitals because of differences in case mix, medical techniques, or quality of care.