Multiplanar CT evaluation of aneurysm rupture signs in subarachnoid hemorrhage

Emergency Radiology - In subarachnoid hemorrhage, noncontrast CT features are used to guide the localization of ruptured aneurysms on CT angiography and DSA. Multiplanar CT may improve the...     

A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor

Cardiac function is modulated by norepinephrine release from innervating sympathetic neurons. These neurons also form excitatory connections onto cardiac myocytes in culture. Here we report that brain-derived neurotrophic factor (BDNF) altered the neurotransmitter release properties of these sympathetic neuron-myocyte connections in rodent cell culture, leading to a rapid shift from excitatory to inhibitory cholinergic transmission in response to neuronal stimulation. Fifteen minutes of BDNF perfusion was sufficient to cause this shift to inhibitory transmission, indicating that BDNF promotes preferential release of acetylcholine in response to neuronal stimulation. We found that p75(-/-) neurons did not release acetylcholine in response to BDNF and that neurons overexpressing p75 showed increased cholinergic transmission, indicating that the actions of BDNF are mediated through the p75 neurotrophin receptor. Our findings indicate that p75 is involved in modulating the release of distinct neurotransmitter pools, resulting in a functional switch between excitatory and inhibitory neurotransmission in individual neurons.     

Enhancing repair of the mammalian heart

The injured mammalian heart is particularly susceptible to tissue deterioration, scarring, and loss of contractile function in response to trauma or sustained disease. We tested the ability of a locally acting insulin-like growth factor-1 isoform (mIGF-1) to recover heart functionality, expressing the transgene in the mouse myocardium to exclude endocrine effects on other tissues. supplemental mIGF-1 expression did not perturb normal cardiac growth and physiology. Restoration of cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by modulation of the inflammatory response and increased antiapoptotic signaling. mIGF-1 ventricular tissue exhibited increased proliferative activity several weeks after injury. The canonical signaling pathway involving Akt, mTOR, and p70S6 kinase was not induced in mIGF-1 hearts, which instead activated alternate PDK1 and SGK1 signaling intermediates. The robust response achieved with the mIGF-1 isoform provides a mechanistic basis for clinically feasible therapeutic strategies for improving the outcome of heart disease.     

Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model

Antipsychotic induced Parkinsonism (AIP) is a common adverse effect of antipsychotic drug treatment among schizophrenia patients. Two previous studies showed association of the rs4606 SNP in the 3' untranslated region of the regulator of G protein signaling 2 gene (RGS2) with susceptibility to AIP. Since rs4606 reportedly influences expression of RGS2, we applied a translational approach and studied the effect of chronic (24 days) exposure to haloperidol on AIP-like features in mice carrying a mutation that causes lower Rgs2 gene expression. Haloperidol and vehicle treated male mice heterozygous (HET) or homozygous (HOM) for the mutation, or wild type (WT), were evaluated for open field locomotion, catalepsy duration, pole test performance and rota-rod latency to fall. We showed that in haloperidol treated mice lower Rgs2 expression is associated with better performance on the open field, catalepsy and rota-rod tests but not the pole test. Results were most consistent for the 0.2 mg/kg/d haloperidol dose. These observations support the possible involvement of RGS2 in mechanisms underlying susceptibility to AIP.     

Proximal tubule overexpression of a locally acting IGF isoform, Igf-1Ea, increases inflammation after ischemic injury

ObjectiveIGF-1 is an important regulator of postnatal growth in mammals. In mice, a non-circulating, locally acting isoform of IGF-1, IGF-1Ea, has been documented as a central regulator of muscle regeneration and has been shown to improve repair in the heart and skin. In this study, we examine whether local production of IGF1-Ea protein improves tubular repair after renal ischemia reperfusion injury.DesignTransgenic mice in which the proximal-tubule specific promoter Sglt2 was driving the expression of an Igf-1Ea transgene. These animals were treated with an ischemic-reperfusion injury and the response at 24 h and 5 days compared with wildtype littermates.ResultsTransgenic mice demonstrated rapid and enhanced renal injury in comparison to wild type mice. Five days after injury the wild type and low expressing Igf-1Ea transgenic mice showed significant tubular recovery, while high expressing Igf-1Ea transgenic mice displayed significant tubular damage. This marked injury was accompanied by a two-fold increase in the number of F4/80 positive macrophages and a three-fold increase in the number of Gr1-positive neutrophils in the kidney. At the molecular level, Igf-1Ea expression resulted in significant up-regulation of proinflammatory cytokines such as TNF-α and Ccl2. Expression of Nfatc1 was also delayed, suggesting reduced tubular proliferation after kidney injury.ConclusionsThese data indicate that, unlike the muscle, heart and skin, elevated levels of IGF-1Ea in the proximal tubules exacerbates ischemia reperfusion injury resulting in increased recruitment of macrophages and neutrophils and delays repair in a renal setting.     

Pelvic enthesopathy on CT is significantly more prevalent in patients with diffuse idiopathic skeletal hyperostosis (DISH) compared with matched control patients

Clinical Rheumatology - The purpose of this study is to evaluate the prevalence of pelvic enthesopathy on computed tomography (CT) in patients with DISH compared to matched control group. Pelvic CT...     

Target cells promote the development and functional maturation of neurons derived from a sympathetic precursor cell line

The role of target interactions in the development and functional maturation of peripheral neurons was investigated using an immortalized sympathetic precursor cell line. bMAH cells underwent neuronal differentiation in response to neurotrophic factors, but maintained an immature neuronal phenotype characterized by small cell bodies and continued cell division. Co-culture with cardiac myocytes, a target of sympathetic innervation, promoted the appearance of large-diameter postmitotic bMAH neurons. Analysis of bMAH maturation in the presence and absence of co-cultured myocytes indicated that myocyte-derived factors promoted the survival of maturing bMAH neurons prior to their acquisition of nerve growth factor dependence. Myocyte interactions also promoted the functional maturation of bMAH neurons, leading to an increase in the localization of synaptic vesicle proteins into neuritic varicosities and the acquisition of sympathetic-like intrinsic electrical properties. Like primary sympathetic neurons, mature bMAH neurons formed functional connections to cardiac myocytes as measured by evoked postsynaptic responses in connected myocytes. The effects of myocyte co-culture on developing bMAH neurons could be mimicked by myocyte conditioned medium, indicating that cardiac myocytes produce soluble factors that promote the appearance of mature neurons. These experiments indicate that targets of innervation play a role in directing the development and final maturation of peripheral neurons.     

The mission of the Director General of the Ministry of Health

In France, the health and solidarity department of Employment and solidarity Ministry have just been re-organised. The Directory General of the department of Health is experiencing a complete revision of its functions and organisation. This article presents the public health context which has been taken into account for this new organisation and explains its main principles and strategic orientations. The new organisation chart is clarified. It is made up by two departments and seven under-directions. Up to now, control and administrative supervision were predominant among Health General Direction functions. They are now oriented to administrate missions prioritizing the function of health doctrines' elaboration, of programmation, animation and coordination. As the guarantor of sanitary security, the Health General Direction has also to impulse a new partnership which does not only include health professional, social and health organisation and the economic actors: citizen in general and service users in particular have to be included to promote health democracy.