Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men.

Data from animal experiments and clinical investigations suggest that components of the renin-angiotensin system are markedly affected by sex hormones. However, whether estrogen affects human atrial myocardium has not been investigated yet. In this study, we determined the effects of estrogen on key components of atrial renin-angiotensin system: angiotensin-converting enzyme, responsible for generation of angiotensin II and angiotensin-converting enzyme 2, counteracting majority of AngII effects, and different renin-angiotensin system receptors, AT1R, AT2R, and MAS. First, the expression levels of estrogen receptors mRNA were determined in right atrial appendages obtained from patients undergoing heart surgery. The amounts of estrogen receptor α and estrogen receptor ß mRNA were similar between women ( n = 14) and men ( n = 10). Atrial tissue slices (350 µm) were prepared from male donors which were exposed to estrogen (1-100 nM; n = 21) or stimulated at 4 Hz for 24 h in the presence or absence of 100 nM estrogen ( n = 16), respectively. The administration of estrogen did not change mRNA levels of estrogen receptors, but activated MAP kinases, Erk1/2. Furthermore, estrogen increased the amounts of angiotensin-converting enzyme 2-mRNA (1.89 ± 0.23; P < 0.05) but reduced that of angiotensin-converting enzyme-mRNA (0.78 ± 0.07, P < 0.05). In addition, the transcript levels of AT2R and MAS were upregulated by estrogen. Pacing of tissue slices significantly increased the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at both the mRNA and protein level. During pacing, administration of estrogen substantially lowered the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at the transcript (0.92 ± 0.21 vs. 2.12 ± 0.27 at 4 Hz) and protein level (0.94 ± 0.20 vs. 2.14 ± 0.3 at 4 Hz). Moreover, estrogen elicited anti-inflammatory and anti-oxidative effects on renin-angiotensin system-associated downstream effectors such as pro-oxidative LOX-1 and pro-inflammatory ICAM-1. An antagonist of estrogen receptor α reversed these anti-inflammatory and anti-oxidative effects of estrogen significantly. Overall, our results demonstrated that estrogen modifies the local renin-angiotensin system homeostasis and achieves protective effects in atrial myocardium from elderly men. Impact statement The present study demonstrates that estrogen affects the human atrial myocardium and mediates protective actions through estrogen receptors-(ER) dependent signaling. Estrogen substantially modulates the local RAS via downregulation of ACE and simultaneous upregulation of ACE2, AT2R and MAS expression levels. This is indicative of a shift of the classical RAS/ACE axis to the alternative, protective RAS/ACE2 axis. In support of this view, estrogen attenuated the expression of RAS-associated downstream effectors, LOX-1, and ICAM-1. A specific antagonist of ERα reversed the anti-inflammatory and anti-oxidative effects of estrogen in paced and non-paced atrial tissue slices. In summary, our data demonstrate the existence of protective effects of estrogen in atrial tissue from elderly men which are at least in part, mediated by the regulation of local RAS homeostasis.

Acidified nitrite: a host defence against colonization with C. difficile spores?

Proton pump inhibitor (PPI) use increases the risk of Clostridium difficile infection (CDI) despite C. difficile spores being acid resistant. Swallowed saliva contains nitrite which reacts with gastric acid, producing bactericidal nitrogen oxides. With 5mM nitrite at pH 2 (reflecting normal gastric conditions) all C. difficile spores were killed within 15 min. No reduction in count was seen with the same nitrite concentration at pH 5, representing gastric conditions in patients taking PPIs, even after 60 min. Reduced gastric acidification of salivary nitrite may explain the increased risk of CDI in patients taking PPIs.

[Dose area product of pediatric VCUG with regard to the strongly lowered German diagnostic reference levels]. / Das MCU bei Kindern. Dosiswerte im klinischen Alltag im Hinblick auf die stark gesenkten diagnostischen Referenzwerte.

PURPOSE: To compare the dose area products of pediatric VCUG in daily practice with the dramatically reduced official German diagnostic reference levels, which are based on selected data. MATERIALS AND METHODS: 413 consecutive pediatric VCUG examinations were analyzed. RESULTS: The mean dose area product of all examinations was 0.97 dGycm². This is below the lowest reference level that is valid for neonates. In 12 cases (5.6 %) the achieved dose area product was higher than the corresponding reference level. CONCLUSION: Using the available techniques for radiation protection, it is possible in the daily routine to meet the official diagnostic reference levels for children, which have been reduced by up to 80 %, even though these levels are based on a selected, possibly non-representative data set.

[Micronodular sonographic pattern of the spleen: a frequent finding in children and adolescents]. / Feinnoduläres Milzparenchym, ein häufiger sonografischer Befund bei Kindern und Jugendlichen.

UNLABELLED: In textbooks about abdominal sonography, the parenchyma of the spleen is described as homogeneous. However, using high-frequency probes, sonography of the spleen in children often reveals a micronodular pattern. AIM: To investigate the prevalence of a micronodular pattern in the pediatric spleen and to evaluate possible correlations to clinical parameters. METHODS: In 106 non-selected children (54 males, 52 females, mean age 7 years 10 months), the spleen was examined with a 17 MHz probe. Simultaneously the size of the spleen was measured, and other parameters such as leukocyte and thrombocyte counts were recorded. The pattern of the spleen was estimated using a four-step scale. 0: homogeneous tissue without micronodular components, 1: faint micronodular pattern/barely perceptible, 2 and 3: micronodular pattern clearly visible of moderate (2) or strong intensity (3). RESULTS: In 33 children a homogenous pattern was found (31.1 %) and in 48 children (45.3 %) a micronodular pattern of the spleen was clearly visible. A statistical correlation to spleen size or leukocyte or thrombocyte count or CRP could not be proven. 52 % of children with an enlarged spleen had a micronodular pattern, as well as 66.7 % of children with leukocytosis, 44.7 % of children with increased CRP, and 54.5 % of children with thrombocytosis. However, there was a strong statistical correlation to the age of the children with a maximum at the age of 1 to 5 years. CONCLUSION: A micronodular pattern of the spleen is frequent in children, even without clinical signs of infection. It is important to be aware of this finding and not to confuse it with pathological changes.

Physicians' perceptions and uses of commercial drug information sources: an examination of pharmaceutical marketing to physicians.

Data were collected from physicians attending a medical conference. This exploratory study was primarily interested in two areas. First, the investigators were interested in better understanding physicians' responses to different promotional tactics typically used by the pharmaceutical industry. Pharmaceutical representatives were most useful, followed by drug samples and infomercials in medical journals. Direct mail, promotional faxes, and promotional products were used less by physicians. Second, the investigators were interested in learning what information sources influenced physicians' drug choices. Physicians were primarily influenced by their prior experience with a drug, then by drug compendiums, and journal articles. Physicians were also influenced by information provided by the industry and other factors, like the drug's price and their patients' financial situations. Managerial implications for marketing to physicians and ideas for future research are discussed.

Reducing conduct problems among children of battered women.

This study was an experimental evaluation of an intervention designed to reduce conduct problems among children of battered women. Participants were 36 families (mothers and children) in which the mother had sought shelter because of relationship violence and had at least 1 child (4-9 years old) with clinical levels of conduct problems. The intervention consisted of 2 primary components: (a) providing instrumental and emotional support and (b) teaching child management skills to mothers. Families were randomly assigned to either the intervention condition or the existing services comparison condition and were assessed on 5 occasions over 16 months after shelter departure. Compared with families receiving existing services, children in the intervention condition improved at a faster rate, the proportion of children displaying clinical levels of conduct problems was greatly diminished, and mothers displayed greater improvements in child management skills.

Neuropsychologic impact of facial deformities in children. Neurodevelopmental role of the face in communication and bonding.

The face is the primary tool of human communication. In early childhood, the face plays a crucial role in bonding and attachment. Severe craniofacial problems may alter bonding and attachment, thereby resulting in future risk for emotional, behavioral, and social problems. Clinical and research findings, while incomplete, suggest that this is the case. This conceptual understanding of the key role of face-to-face communication in early childhood provides a compelling rationale for early repair of craniofacial deformations.

[Evaluation of rapid gradient-echo and turbo-spin-echo sequences in MRT of focal liver lesions using 0.5 tesla]. / Evaluierung schneller Gradienten-Echo- und Turbo-Spin-Echo-Sequenzen in der MRT von fokalen Leberläsionen bei 0.5 Tesla.

The value of rapid T1- and T2-weighted fast field (T1-FFE, T2-FFE) gradient-echo sequences and T2 weighted turbo-spin echo (TSE) sequences in the diagnosis of focal liver lesions using 0.5 Tesla was compared with conventional spin-echo sequences (SE). Amongst 88 liver lesions T1-SE sequences showed 98%, T2-TSE sequences showed 92%, T2-SE sequence showed 84%, T1-FFE sequence showed 78% and T2-FFE sequence showed 69%. Direct comparison has shown that TSE sequences are able to demonstrate significantly more lesions (p < 0.05) than T2-SE sequences. Quantitative assessment has shown that the tumor/liver contrast/noise ratio in the T1-SE sequence was 118% higher than in the T1-FFE sequence (p < 0.001). Comparison of T2 weighted sequences has shown that the tumour/liver contrast/noise ratio was 45% higher in the TSE sequence than in the T2-SE and 239% higher than in the T2-FFE sequence (p < 0.001). The results indicate that the TSE sequence should be used instead of the conventional T2-SE sequence because of the reduced time (about 40%), due to improved image quality and increased demonstration rate of liver lesions. Neither T1-FFE nor T2-FFE are suitable, when using moderate field strength, to replace T1-SE or TSE sequences.

Marketing to rural seniors: opportunities for the service sector.

A recent study of rural Midwestern elderly consumers revealed a need for and interest in purchasing services designed for this sizeable and rapidly growing market. The study investigated the levels of need for 54 proposed services which could be provided through non-governmental institutions (businesses and non-profit organizations), along with the elderly consumer's ability and willingness to pay a "reasonable price" for the services. Based on the research findings, those service categories possessing market potential are presented and recommendations for marketing to rural elderly consumers are discussed.