Conservation of L-type Ca2+ current characteristics in endo- and epicardial myocytes from rat left ventricle with pressure-induced hypertrophy

Cardiac hypertrophy alters the regional distribution of action potential duration by affecting the magnitude and kinetics of underlying ionic currents. In the present study, the effect of pressure-induced cardiac hypertrophy on the magnitude and kinetics of the L-type Ca2+ current ( I(CaL)) was investigated in endo- and epicardial myocytes of the rat left ventricular free wall. Cardiac hypertrophy was induced by stenosis of the ascending aorta (AS), which led to a pressure difference between the left ventricular peak pressure and the peripheral systolic blood pressure of 84+/-6 mmHg ( n=5, P<0.0001). Sham-operated animals served as controls ( n=7). I(CaL) was investigated using the whole-cell patch-clamp technique. The magnitude of I(CaL) as well as its inactivation, steady-state activation, steady-state inactivation and recovery from inactivation were similar in endo- and epicardial myocytes of sham-operated rats. In myocytes isolated from AS animals, I(CaL) magnitude was significantly greater than in sham-operated animals (2407+/-127 pA, n=42 versus 1904+/-102 pA, n=33; P<0.01). This difference disappeared, however, when I(CaL) was normalized to cell capacitance. The kinetic properties of I(CaL) were unaffected by AS in both endo- and epicardial myocytes. In conclusion, in pressure-induced cardiac hypertrophy the density and kinetics of I(CaL) are preserved. This suggests that an additional insertion or recruitment of channels normally underlying I(CaL) into the cell membrane compensates for the increased cell size associated with hypertrophy.     

A mimotope defined by phage display inhibits IgE binding to the plant panallergen profilin

Birch pollen and mugwort pollen allergies are often associated with hypersensitivity to plant foods. This clinical and serological cross-reactivity is mediated by IgE antibodies reacting with homologous proteins in pollen and food. Cross-reacting homologs of the important birch pollen allergen Bet v 2 (profilin) could be detected in other pollen, fruits, nuts, and vegetables, such as celery tuber. We purified IgG/IgE antibodies from the serum of an exclusively profilin-allergic patient using affinity columns either coupled with protein extracts from mugwort pollen, birch pollen, or celery tuber. Constrained and unconstrained random nonapeptide libraries were pooled and screened with the anti-profilin antibody preparations to define cross-reactive ligands. Specific ligands were enriched by successive panning rounds using the profilin-specific antibodies in series. After the last panning round enriched phage clones were screened with purified profilin-specific antibodies and IgE-binding clones were sequenced. Five out of eight positive clones (62.5 %) displayed the same circular peptide CAISGGYPVC. This peptide was synthesized and examined for its ability to inhibit IgE binding to blotted mugwort pollen, birch pollen, or celery tuber profilin. Inhibition studies showed reduction of IgE binding to profilins in all three protein extracts. As the sequence of the mimotope did not show any homology to the known birch profilin sequence this peptide is considered to mimic a common conformational IgE epitope for these examined profilins.     

Metabolic syndrome is associated with impaired health-related quality of life: Lapinlahti 2005 study

Purpose  Association of Metabolic Syndrome (MetS) with Health-Related Quality of Life (HRQoL) is poorly documented. Our objective was to examine this association in an adult general population. Methods  In our cross-sectional community-based health survey in a semirural Finnish community, we invited all the adults (n = 760) of eight birth cohorts between 30 and 65 years, of which 480 (63%) participated. A 15-dimensional, standardized HRQoL instrument (15D) was used to measure the main outcome, and the National Cholesterol Education Programme (NCEP) 2005 criteria were used for MetS classification. Results  The prevalence of MetS was 38%. MetS was significantly associated with impaired HRQoL (P < 0.001) measured by the 15D score. Participants with MetS were statistically significantly worse off than participants without MetS in the dimensions of mobility (P < 0.001), hearing (P = 0.021), breathing (P < 0.001), usual activities (P = 0.001), discomfort and symptoms (P = 0.002), vitality (P = 0.003), and sexual activity (P = 0.008). In a logistic regression analysis, a significant association persisted between MetS and impaired HRQoL (OR = 1.9). Conclusions  MetS seems to be associated closely with perceived HRQoL at community level. Therefore, reduction of risk factors of MetS may improve HRQoL.     

Effectiveness of a new perforated 0.15 mm poly-p-dioxanon-foil versus titanium-dynamic mesh in reconstruction of the orbital floor

Introduction: In recent years a new perforated PDS (poly-p-dioxanon) foil (0.15 mm) has become available and has not yet been proven to be successful in reconstruction of the orbital floor after blow-out-fractures in randomized studies. The main aim of this clinical trial is to compare this new PDS foil with titanium dynamic mesh (0.3 mm) (TD), which is well established in reconstruction of the orbital floor. Patients and Methods: In a prospective multicentre randomized trial, conducted between 1997 and 1998, out of 42 patients with fractures of the orbital floor, 28 patients needing material for reconstruction were randomized to receive either PDS foil or TD. In a comprehensive preoperative and postoperative protocol patients were monitored by the surgeon, radiologist and ophthalmologist with a postoperative follow-up of least 6 months. Results: Maximum defects of the orbital floor were comparable in both groups (PDS group: 13.3 mm, TD group: 13.9 mm). In both groups the surgical procedure was well tolerated, and functional and cosmetic results were evaluated as satisfactory by all patients. Ophthalmological evaluation, performed up to 6 months postoperatively, revealed double vision or vertical strabismus in nine patients (five PDS group, four titanium group). This was not confirmed subjectively in each single patient. Also ex- or enophthalmos, registered in seven patients of the PDS and four of the TD group (mainly +/-1 mm) were not considered as relevant by the patients. Conclusion: The new 0.15 mm perforated PDS foil was comparable to 0.3 mm titanium mesh concerning functional and cosmetic outcome. Obviously, persisting ophthalmometric disorders were compensated very well in both groups. PDS foil is felt to be the preferred material since it is bioresorbable and more convenient to handle. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.     

Carbon Monoxide Production from Desflurane, Enflurane, Halothane, Isoflurane, and Sevoflurane with Dry Soda Lime

Background : Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers.

Methods : Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Drager absorber canister (bottom to top) filled with dried soda lime (Dragersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20[degrees]C). The absorbent temperature was not controlled.

Results : Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively).     

Construct validity of the Offer Self-Image Questionnaire in Finnish 13-year-old adolescents: Differences in the self-images of boys and girls

The construct validity of the Offer Self-Image Questionnaire (OSIQ) was examined among 13-year-old Finns. Questionnaires were completed by 268 pupils at school. The construct validity was studied by means of factor analysis. Factor analysis involving 130 items yielded 5 factors with different content: an anxious self, a coping self, awareness by the adolescents of their place in the world, social relationships, and sexuality. The factor solution was moderately useful; it included most of the original items (71%) and explained 31% of the total variance. Boys were more anxious and had a more negative social and sexual self-image than the girls. The OSIQ estimates adolescents' self-images in a multidimensional manner. When interpreting the scores, it is important to consider sex differences and the developmental stage of the adolescent. Despite its limitations, the OSIQ remains a moderately valid and clinically relevant method for use in the clinical assessment of adolescents.     

Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

High blood pressure is the leading risk factor for death worldwide. One of the hallmarks is a rise of peripheral vascular resistance, which largely depends on arteriole tone. Ca²⁺-activated chloride currents (CaCCs) in vascular smooth muscle cells (VSMCs) are candidates for increasing vascular contractility. We analyzed the vascular tree and identified substantial CaCCs in VSMCs of the aorta and carotid arteries. CaCCs were small or absent in VSMCs of medium-sized vessels such as mesenteric arteries and larger retinal arterioles. In small vessels of the retina, brain, and skeletal muscle, where contractile intermediate cells or pericytes gradually replace VSMCs, CaCCs were particularly large. Targeted disruption of the calcium-activated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes eliminated CaCCs in all vessels studied. Mice lacking vascular TMEM16A had lower systemic blood pressure and a decreased hypertensive response following vasoconstrictor treatment. There was no difference in contractility of medium-sized mesenteric arteries; however, responsiveness of the aorta and small retinal arterioles to the vasoconstriction-inducing drug U46619 was reduced. TMEM16A also was required for peripheral blood vessel contractility, as the response to U46619 was attenuated in isolated perfused hind limbs from mutant mice. Out data suggest that TMEM16A plays a general role in arteriolar and capillary blood flow and is a promising target for the treatment of hypertension.     

Cytokine profile of Plasmodium falciparum-specific T cells in non-immune malaria patients

CD3⁺ T cells are important sources of both pro‐ and anti‐inflammatory cytokines during Plasmodium falciparum malaria. We studied the frequency of interleukin‐2 (IL‐2), gamma interferon (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α) and IL‐10 expressing CD3⁺ cells in 10 non‐immune malaria patients with uncomplicated malaria and in one patient with cerebral malaria after P. falciparum‐specific and non‐specific mitogenic stimulation. Analysis by fluorescence‐activated cell sorting was performed after drug‐induced clearance of parasites to allow previously sequestered T cells to be detected in peripheral blood. CD3⁺ cells of patients responded to P. falciparum infected erythrocytes with significant increases in the percentage of IL‐2, IFN‐γ, and TNF‐α, but also IL‐10, positive cells. CD3⁺ cells from malaria‐naïve donors were also responsive to specific stimulation albeit to a much lesser extent. Mitogenic stimulation of PBMC revealed no significant differences between cells of patients and controls. CD3⁺ cells of the patient with cerebral malaria were hyporesponsive both to the infecting parasite isolate as well as to our laboratory‐adapted P. falciparum isolate, whereas two patients with uncomplicated disease were more responsive to their infecting parasites than to the laboratory‐adapted isolate. The results indicate that the increased responsiveness of in vivo primed compared to malaria‐naïve CD3⁺ cells is Plasmodium‐specific and biased towards production of IFN‐γ and TNF‐α.