Extracellular Na+ removal attenuates rundown of the epithelial Na+-channel (ENaC) by reducing the rate of channel retrieval

Regulation of the epithelial sodium channel (ENaC) is important for the long-term control of arterial blood pressure as evidenced by gain of function mutations of ENaC causing Liddles syndrome, a rare form of hereditary arterial hypertension. In Xenopus laevis oocytes expressing ENaC a spontaneous decline of ENaC currents over time, so-called rundown, is commonly observed. Mechanisms involved in rundown may be physiologically relevant and may be related to feedback regulation of ENaC by intra- or extracellular Na⁺. We tested the effect of extracellular Na⁺ removal on ENaC rundown. Spontaneous rundown of ENaC was largely prevented by extracellular Na⁺ removal and was partially prevented by primaquine suggesting that it is due to endocytic channel retrieval. Liddles syndrome mutation caused a reduced rate of rundown, and in oocytes expressing the mutated channel extracellular Na⁺ removal not only prevented rundown but even increased the ENaC currents (runup). Acute exposure to high extracellular Na⁺ drastically reduced whole-cell currents and surface expression of wild-type ENaC, while these effects were much smaller in ENaC with Liddles syndrome mutation consistent with a stabilization of the mutated channel in the plasma membrane. Interestingly, the apparent intracellular Na⁺ concentration [Na⁺]_i-app was high (>60 mM) in ENaC-expressing oocytes but rundown was not associated with a further increase in [Na⁺]_i-app. We conclude that the inhibitory effect of extracellular Na⁺ removal on rundown is due to an inhibition of endocytic ENaC retrieval.     

A classification of plant food allergens

Plant food allergens can be classified into families and superfamilies on the basis of their structural and functional properties. The most widespread groups of plant proteins that contain allergens are the cupin and prolamin superfamilies and the protein families of the plant defense system. The cupin superfamily includes allergenic seed storage proteins of the vicilin and legumin type present in soybeans, peanuts, and tree nuts. The prolamin superfamily includes several important types of allergens of legumes, tree nuts, cereals, fruits, and vegetables, such as the 2S albumin seed storage proteins, the nonspecific lipid transfer proteins, and the cereal alpha-amylase and protease inhibitors. Plant food allergens are also found among the various groups of defense proteins that enable plants to resist biotic and abiotic stress, such as the pathogenesis-related proteins, certain proteases, and protease inhibitors. This review focuses on a classification system of plant food allergens that is emerging from the synopsis of allergology and protein evolution.     

Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer cells

Vitamin D and its analogues are potent regulators of cell growth and differentiation both in vivo and in vitro. We studied the effects of 25-hydroxyvitamin D(3) [25(OH)D(3)], 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and vitamin D analogue, EB 1089, on the growth of a human ovarian cancer cell line, OVCAR-3. We also studied the expression of vitamin D metabolising enzymes 24-hydroxylase (24OHase) and 1alpha-hydroxylase (1alphaOHase). Our results showed that high concentrations (10 and 100 nM) of 1,25(OH)(2)D(3) inhibited a cell proliferation, whereas low concentration (0.1 nM) stimulated growth of the OVCAR-3 cells. In the concentration range of 10-500 nM a prohormone, 25(OH)D(3), stimulated growth. An amount of 1 nM EB 1089 and 100 nM 1,25(OH)(2)D(3) inhibited growth with an equal magnitude. The expression of 24OHase was strongly induced by 1,25(OH)(2)D(3) and EB 1089 in OVCAR-3 cells, and analysis of vitamin D metabolites showed the functionality of 24OHase. An inhibition of 24OHase activity with a novel 24OHase inhibitor enhanced growth-inhibiting effects of 1,25(OH)(2)D(3) and suppressed the growth stimulation of 100 nM 25(OH)D(3). We also report the expression of a vitamin D activating enzyme, 1alphaOHase, in 7 ovarian cancer cell lines. The production of 1,25(OH)(2)D(3) in OVCAR-3 cells was low, possibly due to an extensive activity of 24OHase or a low 1alphaOHase activity. These results suggest that in ovarian cancer cells vitamin D metabolizing enzymes might play a key role in modulating the growth response to vitamin D. The possible mitogenic effects of vitamin D should be considered when evaluating treatment of ovarian cancer with vitamin D.     

Austrian infliximab experience in Crohn's disease: a nationwide cooperative study with long-term follow-up

OBJECTIVE: To determine the nationwide experience with infliximab for the treatment of Crohn's disease in Austria. DESIGN: National multicentre retrospective postal questionnaire survey. SETTING AND PARTICIPANTS: All institutions using infliximab for Crohn's disease in the years 1999 and 2000 were identified by the registry of the local provider of this drug. OUTCOME MEASURES: Response after first treatment course according to physician global assessment, number of subsequent infliximab infusions, disease activity at end of follow-up, avoidance of steroids, frequency of surgery for Crohn's disease, and adverse events. RESULTS: Questionnaires were returned by 32/35 (91%) centres approached. A total of 748 infusions were administered to 153 patients. After the first treatment course an excellent or good response occurred in 48/58 (83%) patients with luminal disease, and in 67/95 (71%) patients with fistulous disease (P < 0.05). After the first treatment course 108 (71%) patients received further infliximab therapy. At a mean follow-up of 29 months, 50% of patients had improved since baseline without requiring surgery for Crohn's disease. Steroid withdrawal was achieved in 25% of patients. Surgery had been performed in one-third of patients and was associated with lacking response to the first treatment course (P < 0.001) and with fistulous disease (P = 0.012). Co-medication with azathioprine favoured the initial response and steroid withdrawal (P < 0.05). One patient died from myocarditis; other adverse events were consistent with that seen in other studies of infliximab. CONCLUSIONS: The Austrian experience with infliximab for Crohn's disease is in general accordance with results from clinical trials and post-marketing studies from single centres. A substantial subgroup of patients appear to have a prolonged benefit from infliximab therapy.     

Life satisfaction and depression in a 15-year follow-up of healthy adults

OBJECTIVE: The aim of this study was to investigate the cross-sectional and longitudinal relationship between life satisfaction and depressive symptoms in healthy adults. METHOD: This is a 15-year prospective cohort study with a nationwide sample of healthy Finnish adults (N = 9679), aged 18-45, who responded to postal questionnaires in 1975, 1981 and 1990 including a 4-item life satisfaction (LS) scale (range 4-20) and, in 1990, the 21-item Beck Depression Inventory (BDI). RESULTS: A strong linear association was found between concurrent LS and BDI scales (r = 0.6). With an LS cut-off point of 11/12, moderate/severe depression (BDI > or = 19) was detected with 87% sensitivity, 88 % specificity and a 94% area under the ROC curve. Longitudinally, a strongly increased risk of moderate/severe depression in 1990 was observed among the dissatisfied (LS 12-20) compared with the satisfied (LS 4-6) in 1975 (OR = 6.7; 95 %CI 4.2-10.9) and in 1981 (OR = 10.4; 6.1-17.6). CONCLUSION: The 4-item LS scale can identify a group of healthy people from the general population with a high risk of having or developing depressive symptoms. Since low life satisfaction also indicates an elevated risk of other adverse health outcomes, the assessment of subjective well-being should be encouraged both in surveys and in clinical practice.     

<Superscript>123</Superscript>I-β-CIT binding and recovery from depression

Abstract. Eighteen depressive outpatients were investigated using single-photon emission computerized tomography (SPECT) with a high-affinity dopamine (DA) and serotonin transporter (SERT) specific radioligand, ¹²³I-labeled -CIT (2-carbomethoxy-3-(4-iodophenyl)-tropane). The patients were tested at the beginning of the study and on follow-up after six months. The severity of depression was evaluated using the 17-item Hamilton Rating Scale of Depression (HRSD). Eight of the eighteen patients had an HRSD score below the median (12 points) on follow-up, and they had a significantly greater increase in ¹²³I--CIT binding in the midbrain region compared with those patients who did not recover (ANCOVA: F = 8.12; df = 1, 14; p = 0.013). These results indicate that recovery from depression is associated with an increase in ¹²³I--CIT binding in the midbrain.     

Do stressful life-events or sociodemographic variables associate with depression and alexithymia among a general population?--A 3-year follow-up study

This 3-year follow-up study examined background factors, stressful life-events, and changes in alexithymia and depression scores in four groups of subjects from a general population (N = 1,339): alexithymic (A), depressed (D), simultaneously alexithymic/depressed (AD), and non-alexithymic/non-depressed (O). Alexithymia was assessed using the 20-item version of the Toronto Alexithymia Scale (TAS) and depression using the 21-item Beck Depression Inventory (BDI). A questionnaire screening sociodemography and stressful life-events was also used. The results showed that alexithymia was associated with male gender and blue-collar working, whereas depressive symptoms associated with female gender, older age, poor subjective health, poor financial situation, and low life satisfaction. During the follow-up the sum of stressful life-events was higher among groups AD and D than in groups A and O. The most common stressful life-events were the death of a close relative or friend, a negative change in the health of a family member, and financial problems. The TAS scores decreased only in groups A and AD. The BDI scores decreased in group AD but remained relatively unchanged in group D. Interestingly, if only those without depressive symptoms are considered, alexithymia appears to be a rarer phenomenon than has been reported previously. Furthermore, it seems that depressive symptoms were chronic and long-lasting among the general population.     

Alexithymia and suicidal ideation: a 12-month follow-up study in a general population

Alexithymic features are often associated with depression, which is the most important risk factor for suicidal behaviors. Nevertheless, little is known about the associations between alexithymia and suicidality. In this 12-month follow-up study we investigated the relationship between alexithymia and suicidal ideation in a sample of the general population (N = 1,563) using the 20-item Toronto Alexithymia Scale (TAS-20) and the 21-item Beck Depression Inventory (BDI). Suicidal ideation was more common among subjects with alexithymia than among nonalexithymic subjects (32% v 9% at baseline and 36% v 9% after 12 months). In cross-sectional analyses, alexithymia associated with the presence of suicidal ideation even after adjustment for sex, age, and several psychosocial and socioeconomic factors and the presence of depression. Moreover, after adjustment for depression at baseline, the decrease and increase in alexithymic features during the study period associated independently with recovery from and the occurrence of suicidal ideation, respectively. Nevertheless, these associations were no longer independent when adjusted for concomitant changes in the level of depressive symptoms. In conclusion, if depression presents alexithymic features the subject has an additive impact on the risk of suicidal ideation.