Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma

Allergic asthma is a chronic inflammatory disease of the airways. Of the different lower airway-infiltrating immune cells that participate in asthma, T lymphocytes that produce Th2 cytokines play important roles in pathogenesis. These T cells are mainly fully differentiated CCR7⁻ effector memory T (T_EM) cells. Targeting T_EM cells without affecting CCR7⁺ naïve and central memory (T_CM) cells has the potential of treating T_EM-mediated diseases, such as asthma, without inducing generalized immunosuppression. The voltage-gated K_V1.3 potassium channel is a target for preferential inhibition of T_EM cells. Here, we investigated the effects of ShK-186, a selective K_V1.3 channel blocker, for the treatment of asthma. A significant proportion of T lymphocytes in the lower airways of subjects with asthma expressed high levels of K_V1.3 channels. ShK-186 inhibited the allergen-induced activation of peripheral blood T cells from those subjects. Immunization of F344 rats against ovalbumin followed by intranasal challenges with ovalbumin induced airway hyper-reactivity, which was reduced by the administration of ShK-186. ShK-186 also reduced total immune infiltrates in the bronchoalveolar lavage and number of infiltrating lymphocytes, eosinophils, and neutrophils assessed by differential counts. Rats with the ovalbumin-induced model of asthma had elevated levels of the Th2 cytokines IL-4, IL-5, and IL-13 measured by ELISA in their bronchoalveolar lavage fluids. ShK-186 administration reduced levels of IL-4 and IL-5 and induced an increase in the production of IL-10. Finally, ShK-186 inhibited the proliferation of lung-infiltrating ovalbumin-specific T cells. Our results suggest that K_V1.3 channels represent effective targets for the treatment of allergic asthma.     

Migraine and risk of ischaemic stroke: a case-control study.

OBJECTIVES--To determine whether migraine is a risk factor for ischaemic stroke. DESIGN--A case-control study. SETTING--Two hospitals in Paris. SUBJECTS--212 patients with stroke (137 men and 75 women) and 212 controls matched for sex, age (to within five years), and history of hypertension. MAIN OUTCOME MEASURES--Ischaemic stroke, confirmed by brain computed tomography or magnetic resonance imaging, and history of headache, recorded with structured questionnaire during interview. RESULTS--Prevalence of migraine did not differ between patients with stroke and controls: 18/137 v 17/137 for men (odds ratio 1.1 (95% confidence interval 0.5 to 2.2), p = 0.86); 23/75 v 17/75 for women (odds ratio 1.6 (0.7 to 3.5), p = 0.24); and 41/212 v 34/212 for both sexes (odds ratio 1.3 (0.8 to 2.3), p = 0.33). When subjects were split into two age groups, however, prevalence of migraine was significantly higher among younger women (aged < 45) with stroke compared with their controls (13/20 v 6/20, odds ratio 4.3 (1.2 to 16.3), p = 0.03). Furthermore, the risk of ischaemic stroke was higher among younger women who smoked (7/20 v 1/20, odds ratio 10.2 (1.1 to 93.3)). CONCLUSIONS--Prevalence of migraine was not different between patients with stroke and matched controls except among women aged < 45, when migraine and stroke were significantly associated.     

Age and growth of the European catfish (Silurus glanis) in a Turkish Reservoir and comparison with introduced populations

The European catfish, Silurus glanis, is native to eastern Europe and western Asia and is among the largest freshwater fish in the world. Despite its increasing economic importance and its frequent introductions, the ecology and life-history of this species is poorly known due to the difficulty of sampling such a large species in large rivers and standing waters. Our study provides the first data on age and growth of this species in Turkish waters, where it is native. We report the length-weight relationships and age and size structure of this population, which were significantly different between females and males. A marginal increment analysis indicated that annulus formation occurred between May and June. The estimates of three growth functions (von Bertalanffy, logistic and Gompertz) are reported, with the von Bertalanffy growth providing a better fit and more realistic parameter estimates. Growth rates were significantly higher in males than in females and were overall higher compared to other native populations but similar to introduced populations of similar latitude.     

Magnetic field-induced Ca2+ intake by mesenchymal stem cells is mediated by intracellular Zn2+ and accompanied by a Zn2+ influx

Chronic exposure to magnetic fields (MFs) has a diverse range of effects on biological systems but definitive molecular mechanisms of the interaction remain largely unknown. One of the most frequently reported effects of MF exposure is an elevated concentration of intracellular Ca²⁺ through disputed pathways. Other prominent effects include increased oxidative stress and upregulation of neural markers through EGFR activation in stem cells. Further characterization of cascades triggered by MF exposure is hindered by the phenotype diversity of biological models used in the literature. In an attempt to reveal more mechanistic data in this field, we combined the most commonly used biological model and MF parameters with the most commonly reported effects of MFs.Based on clues from the pathways previously defined as sensitive to MFs (EGFR and Zn²⁺-binding enzymes), the roles of different types of channels (voltage gated Ca²⁺ channels, NMDA receptors, TRP channels) were inquired in the effects of 50 Hz MFs on bone marrow-derived mesenchymal stem cells. We report that, an influx of Zn²⁺ accompanies MF-induced Ca²⁺ intake, which is only attenuated by the broad-range inhibitor of TRP channels and store-operated Ca²⁺ entry (SOCE), 2-Aminoethoxydiphenyl borate (2-APB) among other blockers (memantine, nifedipine, ethosuximide and gabapentin). Interestingly, cation influx completely disappears when intracellular Zn²⁺ is chelated. Our results rule out voltage gated Ca²⁺ channels as a gateway to MF-induced Ca²⁺ intake and suggest Zn²⁺-related channels as a new focus in the field.     

Chickpea Ascochyta Blight: Disease Status and Pathogen Mating Type Distribution in Syria

Chickpea fields were surveyed in nine major chickpea‐growing provinces of Syria in 2008 and 2009 to determine the prevalence and severity of Ascochyta blight, and the distribution of Didymella rabiei mating types (MATs) in the country. A total of 133 Ascochyta rabiei isolates were assayed for mating type, including isolates from older collections that date back to 1982. Multiplex MAT‐specific PCR with three primers was used for MAT analysis. Out of the 133 tested isolates, 64% were MAT1‐1 and 36% were MAT1‐2. Both MATs were found in six provinces but MAT1‐1 alone was found in three provinces. Chi‐squared analysis was used to test for a 1 : 1 ratio of MAT frequencies in all samples. The MAT ratios in the six provinces were not significantly different from 1 : 1, suggesting that there is random mating of the pathogen population under natural conditions. The presence of the two MATs is expected to play a role in the evolution of novel virulence genes that could threaten currently resistant chickpea varieties. Overall analysis of the 133 isolates showed a significant deviation from the 1 : 1 ratio with almost twice as many MAT1‐1 isolates than MAT1‐2 isolates, which indicates a competitive advantage associated with MAT1‐1 in Syria. However, the overall picture of an unequal frequency in MATs indicates that there may be limited sexual recombination occurring in the Syrian population.     

The effects and interactions of three invasive fish species introduced to the aquatic ecosystem of a Turkish Lake (Eğirdir Lake)

We studied feeding behavior and prey selection of topmouth gudgeon (Pseudorasbora parva), big-scale sand smelt (Atherina boyeri) and pike-perch (Sander lucioperca) in Lake E?irdir, the second largest freshwater lake in Turkey. Fish specimens were collected between January and August in 2010 and 2011 using gill-nets and purse seines. A total of 941 specimens were analyzed for stomach contents analysis. We expressed the importance of the food items present in their guts with the relative importance index (IRI) and estimated their diet selectivity indices with Pearre’s index. Pseudorasbora parva had a diverse diet comprising mainly Nitokra hibernica (copepod), Chydorus sphaericus, and Bosmina longirostris (cladoceran) (each, at p?<?0.01), but Chironomus sp. (insect) was not a significant component of its diet (p?>?0.05). Big-scale sand smelt often preferred B. longirostris, N. hibernica, and Alona quadrangularis (each at p?<?0.01). Pike-perch positively, but not statistically significant, selected Atherina boyeri (p?>?0.05), Carassius gibelio was not preferred by pike-perch as food item (p?>?0.05). Our results indicate that invasive species altered the food chain in Lake E?irdir. Thus, because these fish species constitute a major threat for native fish species for food and breeding grounds, extensive care should be taken to prevent invasive fish species entering lakes in Turkey.