Ultraviolet Light Induced Generation of Reactive Oxygen Species.

As ultraviolet (UV) radiation is naturally and ubiquitously emitted by the sun, almost everyone is exposed to it on a daily basis, and it is necessary for normal physiological function. Human exposure to solar UV radiation thus has important health implications. The generation of reactive oxygen species (ROS) by UV radiation is one of the mechanisms through which UV light can manifest its possible detrimental effects on health. When an imbalance develops due to ROS generation exceeding the body's antioxidant defence mechanisms, oxidative stress can develop. Oxidative stress can lead to cellular damage (e.g. lipid peroxidation and DNA fragmentation), apoptosis and cell death. Broadly UV can induce ROS by affecting the cellular components directly or by means of photosensitization mechanisms. More specifically UV light can induce ROS by affecting the enzyme catalase and up-regulating nitric oxide synthase (NOS) synthesis. It may also cause a decrease in protein kinase C (PKC) expression leading to increased ROS production. UVR is capable of modifying DNA and other chromophores resulting in elevated ROS levels. The effects of raised ROS levels can vary based on the intracellular oxidant status of the cell. It is therefore important to protect yourself against the potentially harmful effects of UV light as it can lead to pathological UV-induced ROS production.

The burden and management of FXIII deficiency.

Factor XIII congenital deficiency (FXIII CD) is a serious bleeding disorder resulting in a lifelong bleeding tendency, defective wound healing and recurrent miscarriage. The aim of this study was to review available literature on the burden and management of FXIII CD. To this end, Medline, Embase and Cochrane databases were searched. In current literature, FXIII CD is described as one of the most severe forms of a congenital coagulation disorder, primarily due to a high risk of severe bleeding events. The published literature suggests that over 50% of untreated FXIII CD patients experience severe bleeding symptoms. Intracranial haemorrhage (ICH)--a major cause of death and morbidity--is reported to occur in up to one-third of patients. Nonetheless, data on the social and financial burden in patients with FXIII CD are sparse. Identified reports on the effectiveness and safety of recommended treatments support that patients with FXIII CD should receive prophylactic treatment as early as possible in their lives to prevent the occurrence of bleeds, including potentially life-threatening ICHs. In conclusion, limited data on the social and economic consequences related specifically to FXIII CD have been published to date. However, it is widely acknowledged that the high risk of severe bleeds and ICH results in a high level of burden in patients with bleeding disorders. To inform future clinical decision-making and reimbursement decisions, further research is required to gain insight in how specifically FXIII CD affects quality of life and to fully understand associated economic consequences.

Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.

Genetic factors contribute to the risk of sudden death from cardiac arrhythmias. Here, positional cloning methods establish KVLQT1 as the chromosome 11-linked LQT1 gene responsible for the most common inherited cardiac arrhythmia. KVLQT1 is strongly expressed in the heart and encodes a protein with structural features of a voltage-gated potassium channel. KVLQT1 mutations are present in affected members of 16 arrhythmia families, including one intragenic deletion and ten different missense mutations. These data define KVLQT1 as a novel cardiac potassium channel gene and show that mutations in this gene cause susceptibility to ventricular tachyarrhythmias and sudden death.

Prolonged or repeated copulation and male longevity in the tick Ixodes rubicundus.

Male Ixodes rubicundus were found in copula with attached females in 59% of individuals. The number of males attaching to the female integument or to the the host negligible. In laboratory experiments, males enclosed with females in a small vial had significantly longer life spans than solitary males. Paired males were found to be in copula on 20-34% of observations. Solitary males lost weight while paired males gained weight over a 2-day period. However, the specific energy content of the 2 groups remained constant.

Estrogen effects in the myocardium: inhibition of NF-kappaB DNA binding by estrogen receptor-alpha and -beta.

We have previously shown that estrogen effects in the heart include direct hormone effects on the myocardium. In a recent study we found that one beneficial effect of estradiol on the myocardium is the inhibition of apoptosis in cardiac myocytes. This effect was associated with a reduction of NF-kappaB activity. In the present study we have analyzed the functional mechanism of NF-kappaB inhibition in the myocardium by estrogen receptors-alpha and -beta. Despite the previous finding that 17-beta-estradiol (10 nM) inhibited the staurosporine-induced binding of p65/p50 NF-kappaB complexes to their cognate DNA elements in cultured rat cardiac myocytes, myocyte extracts showed no change in expression or cellular localization of p65, p50, and IkappaB upon staurosporine or estradiol treatment. Addition of either estrogen receptor-alpha or estrogen receptor-beta as recombinant protein was sufficient to inhibit staurosporine-dependent p65/p50 DNA binding in cardiac myocytes. 17-beta-Estradiol inhibits staurosporine-induced p65/p50 DNA binding associated with apoptotic cell death of cardiac myocytes via estrogen receptors-alpha and -beta. This is not associated with changes in p65, p50 and IkappaB expression or subcellular localization. Thus, inhibition of NF-kappaB activity by estrogenic compounds might inhibit NF-kappaB dependent gene expression such as pro-inflammatory cytokines in the myocardium.

Effects of benzo(a)pyrene and size of organic matter particles on bioaccumulation and growth of Asellus aquaticus.

The effects of sediment-bound toxicants to aquatic invertebrates may vary due to differences in bioavailability, food quality, or food structure. The equilibrium partitioning theory (EPT) assumes that organic matter content of sediments and not structure of organic matter is relevant for biological effects of polycyclic aromatic hydrocarbons. To test this hypothesis effects of benzo(a)pyrene (B(a)P) and size of sediment organic matter particles on the bioaccumulation and growth of the waterlouse Asellus aquaticus were studied in laboratory microcosms. Sediments and A. aquaticus were both sampled in an unpolluted, spring-fed pond. The sampled sediment was divided into two portions. From one portion the size of the organic matter particles was mechanically reduced. One set of each sediment fraction (fine and coarse) was spiked with B(a)P and incubated for 3 weeks resulting in a concentration of 70 mg B(a)P per kg sediment. Bioassays of 32 days were performed in a 2 x 2 factorial design with four replicas of each treatment. The results showed that the growth of A. aquaticus was mainly influenced by the size of organic matter particles. Growth was significantly less (27%) on finer sediments than on coarser sediments. The increase in length was 9-14% lower in the spiked sediments, but this difference was not significant. The reduced growth of A. aquaticus on finer sediments may be due to a change in the availability and/or quality of food together with a change in feeding behavior. The coarse and fine spiked sediment types did not differ significantly with respect to the sediment water partition coefficient, the organic carbon water partition coefficient, and the bioconcentration factor. In contrast, the biota to sediment accumulation factors were significantly 15% higher in the cosms with coarse sediments than in cosms with fine sediments. However, this difference is too small to conflict with EPT.

Mechanisms of estrogen receptor action in the myocardium. Rapid gene activation via the ERK1/2 pathway and serum response elements.

We have previously shown that the myocardium is a target tissue for estrogen. Here, we have identified rapid non-nuclear estrogen effects on the expression of the early growth response gene-1 (Egr-1) in cardiomyocytes. Egr-1 mRNA and protein were rapidly and strongly induced by estrogen in an estrogen receptor-dependent manner via the extracellular signal-regulated kinase, ERK1/2. A promoter analysis study of a 1.2-kilobase Egr-1 promoter fragment revealed that the serum response elements (SREs) but not the estrogen response elements or AP-1 sites are responsible for Egr-1 induction by estrogen, identifying a novel mechanism of estrogen receptor-dependent gene activation in the myocardium. Both estrogen receptor-alpha and -beta induced the Egr-1 promoter via the SREs as well as an artificial promoter consisting of only five SREs in cardiomyocytes. Electrophoretic mobility shift assays showed that a protein complex containing serum response factor or an antigenically related protein was recruited to the SREs by estrogen treatment of primary cardiomyocytes. The recruitment of the protein complex was inhibited by the specific estrogen receptor antagonist ICI 182,780 as well as the MEK inhibitor PD 98059. Taken together, these results identify SREs as important promoter control elements for an estrogen receptor-dependent mechanism of gene activation in the myocardium.

Evidence of a long QT founder gene with varying phenotypic expression in South African families.

We report five South African families of northern European descent (pedigrees 161, 162, 163, 164, and 166) in whom Romano-Ward long QT syndrome (LQT) segregates. The disease mapped to a group of linked markers on chromosome 11p15.5, with maximum combined two point lod scores, all generated at theta = 0, of 15.43 for the D11S922, 10.51 for the D11S1318, and 14.29 for the tyrosine hydroxylase (TH) loci. Recent studies have shown that LQT is caused by an Ala212Val mutation in a potassium channel gene (KVLQT1) in pedigrees 161 to 164. We report that the same mutation is responsible for the disease in pedigree 166. Haplotype construction showed that all the families shared a common haplotype, suggesting a founder gene effect. DNA based identification of gene carriers allowed assessment of the clinical spectrum of LQT. The QTc interval was significantly shorter in both carriers and non-carriers in pedigree 161 (0.48 s and 0.39 s, respectively) than the same two groups in pedigree 161 (0.52 s and 0.42 s, respectively). The spectrum of clinical symptoms appeared more severe in pedigree 162. The possible influence of modulating genetic factors, such as HLA status and sex of family members, on the expression of an LQT founder gene is discussed.