Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity.

Knockout (KO) mice lacking steroidogenic factor 1 (SF-1) exhibit a phenotype that includes adrenal and gonadal agenesis, impaired gonadotropin expression, and abnormalities of the ventromedial hypothalamic nucleus (VMH). Studies in rodents with lesions of the ventromedial hypothalamus have implicated the VMH in body weight regulation, suggesting that SF-1 KO mice may provide a genetic model of obesity. To prevent death, SF-1 KO mice were rescued with corticosteroid injections, followed by syngeneic adrenal transplants from wild-type (WT) littermates. Corticosterone and ACTH levels in WT and SF-1 KO mice were indistinguishable, documenting restoration of hypothalamic-pituitary-adrenal function. Although weights at earlier ages did not differ significantly from WT littermates, SF-1 KO mice were significantly heavier by 8 wk of age and eventually weighed almost twice as much as WT controls. Obesity in SF-1 KO mice predominantly resulted from decreased activity rather than increased food intake. Leptin was increased markedly, insulin was modestly elevated, and glucose was indistinguishable from WT mice. Although sex steroids in rodents affect weight, ovariectomy did not abolish the weight difference between WT and SF-1 KO mice. These SF-1 KO mice are a genetic model of late-onset obesity that may help elucidate the role of the VMH in weight regulation.     

Hypothyroidism and heart failure

Effects of thyroid gland hormones on cardiovascular system have been known for many years. Thyroid gland hormones deficiency is connected with a range of metabolic and hemodynamic changes which can contribute to a genesis of heart failure. Recent works refer to an importance of connection of thyroid gland hormones metabolism with heart insufficiency pathophysiology. That is especially a syndrome of a low trijodthyronin level marked as euthyroid sick syndrome which is significantly more frequent in patients with chronic heart failure compared to a population of healthy individuals. Recent clinical works proved that treatment administration of thyroid gland hormones to patients with heart failure is connected with favourable hemodynamic changes and increased working capacity if the treatment is well tolerated.     

The picture of hypertrophic cardiomyopathy in the elderly

The aim of the study was to analyse the findings obtained in 27 patients with hypertrophic cardiomyopathy who lived to be 60 and more. Elderly patients are, more frequently than younger ones, women, mostly with a negative family history (81% vs. 30% in younger patients), with a lower incidence of syncope (11% vs. 25%), smaller myocardial wall thickness and lesser extent of hypertrophy. Elderly patients displayed mitral ring calcification more often (18%) than younger subjects (6%) or those of the same age but free of hypertrophic cardiomyopathy (3%). Pathological Q waves on the ECG recording were likewise less frequent (7.6% vs. 20.4%). While elderly patients exhibited manifest proneness to elevated values of left ventricular end-diastolic pressure, there were no marked differences in obstruction.     

Molecular lesions in colorectal cancer: impact on prognosis? Original data and review of the literature

BACKGROUND: In the Dukes' B and C stages of colorectal carcinoma there are considerable variations in the observed courses of the disease. Since post-operative chemotherapy in patients with Dukes' C (node-positive) colon carcinoma has been demonstrated to be effective in improving overall-survival, a more exact prognosis assessment gains additional significance and therapeutic relevance. DISCUSSION: One also hopes to derive improved prognostic factors from the clarification of the molecular pathogenesis. Because of its frequency and the accessibility and recognizability of its developmental stages colorectal carcinoma is among the best investigated of all solid tumors. Despite a multitude of suggested molecular candidate markers none of these changes has yet been able enter the everyday life of the clinic. However, it is to be expected that some of the molecular alterations presently discussed will gain importance before long in the clinical treatment of patients with colorectal carcinoma. CONCLUSION: Considering also our own findings, this review presents the latest developments in the scientific discussion of the tumor suppressor/oncogenes p53, k-ras, and DCC, biochemical determinants of the 5-fluorouracil metabolism, and defects of the DNA repair system.     

Effects of intranasal oxytocin on pupil dilation indicate increased salience of socioaffective stimuli

To investigate the mechanisms by which oxytocin improves socioaffective processing, we measured behavioral and pupillometric data during a dynamic facial emotion recognition task. In a double‐blind between‐subjects design, 47 men received either 24 IU intranasal oxytocin (OXT) or a placebo (PLC). Participants in the OXT group recognized all facial expressions at lower intensity levels than did participants in the PLC group. Improved performance was accompanied by increased task‐related pupil dilation, indicating an increased recruitment of attentional resources. We also found increased pupil dilation during the processing of female compared with male faces. This gender‐specific stimulus effect diminished in the OXT group, in which pupil size specifically increased for male faces. Results suggest that improved emotion recognition after OXT treatment might be due to an intensified processing of stimuli that usually do not recruit much attention.     

Myopodin is an F-actin bundling protein with multiple independent actin-binding regions

The assembly of striated muscle myofibrils is a multistep process in which a variety of proteins is involved. One of the first and most important steps in myofibrillogenesis is the arrangement of thin myofilaments into ordered I-Z-I brushes, requiring the coordinated activity of numerous actin binding proteins. The early expression of myopodin prior to sarcomeric α-actinin, as well as its binding to actin, α-actinin and filamin indicate an important role for this protein in actin cytoskeleton remodelling with the precise function of myopodin in this process yet remaining to be resolved. While myopodin was previously described as a protein capable of cross-linking actin filaments into thick bundles upon transient transfections, it has remained unclear whether myopodin alone is capable of bundling actin, or if additional proteins are involved. We have therefore investigated the in vitro actin binding properties of myopodin. High speed cosedimentation assays with skeletal muscle actin confirmed direct binding of myopodin to F-actin and showed that this interaction is mediated by at least two independent actin binding sites, found in all myopodin isoforms identified to date. Furthermore, low-speed cosedimentation assays revealed that not only full length myopodin, but also the fragment containing only the second binding site, bundles microfilaments in the absence of accessory proteins. Ultrastructural analysis demonstrated that this bundling activity resembled that of α-actinin. Biochemical experiments revealed that bundling was not achieved by myopodin’s ability to dimerize, indicating the presence of two individual F-actin binding sites within the second binding segment. Thus full length myopodin contains at least three F-actin binding sites. These data provide further understanding of the mechanisms by which myopodin contributes to actin reorganization during myofibril assembly.

     

Intra-bone nuclear DNA variability in Second World War metatarsal and metacarpal bones

International Journal of Legal Medicine - DNA analysis of Second World War skeletal remains is challenging because of the limited yield of DNA that is usually recovered. Recent forensic research...     

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

Purpose:To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF).Methods:Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T₁ and T₂ values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance.Results:The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P < 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T₁ value in the cerebellar WM and GM, the T₁ value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T₂ in the gray or white matter at any of the time points.Conclusion:Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.