Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study

Background The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. Methods Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. Results Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8-10 min of citalopram infusion. Conclusions Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine

Aldosterone Antagonists in Monotherapy Are Protective against Streptozotocin-Induced Diabetic Nephropathy in Rats

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers

Formation of a protein corona on the surface of extracellular vesicles in blood plasma

In this study we tested whether a protein corona is formed around extracellular vesicles (EVs) in blood plasma. We isolated medium-sized nascent EVs of THP1 cells as well as of Optiprep-purified platelets, and incubated them in EV-depleted blood plasma from healthy subjects and from patients with rheumatoid arthritis. EVs were subjected to differential centrifugation, size exclusion chromatography, or density gradient ultracentrifugation followed by mass spectrometry. Plasma protein-coated EVs had a higher density compared to the nascent ones and carried numerous newly associated proteins. Interactions between plasma proteins and EVs were confirmed by confocal microscopy, capillary Western immunoassay, immune electron microscopy and flow cytometry. We identified nine shared EV corona proteins (ApoA1, ApoB, ApoC3, ApoE, complement factors 3 and 4B, fibrinogen alpha-chain, immunoglobulin heavy constant gamma 2 and gamma 4 chains), which appear to be common corona proteins among EVs, viruses and artificial nanoparticles in blood plasma. An unexpected finding of this study was the high overlap of the composition of the protein corona with blood plasma protein aggregates. This is explained by our finding that besides a diffuse, patchy protein corona, large protein aggregates also associate with the surface of EVs. However, while EVs with an external plasma protein cargo induced an increased expression of TNF-alpha, IL-6, CD83, CD86 and HLA-DR of human monocyte-derived dendritic cells, EV-free protein aggregates had no effect. In conclusion, our data may shed new light on the origin of the commonly reported plasma protein 'contamination' of EV preparations and may add a new perspective to EV research.11Ysciescopu

Western blot analysis of Na/K ATPase (NKA).

<p>Aldosterone antagonists were the most effective in decreasing diabetes and hyperglycemia induced elevation of tubular NKA protein level. Top panel: Representative examples of Western blot analysis. Lower panels: <i>A</i>: Densitometric analysis of NKA protein levels in kidney homogenates of control, diabetic and treated diabetic rats. <i>B</i>: Densitometric analysis of NKA protein levels in HK-2 tubular cells. Bar graph represents densitometric analysis from multiple experiments. Data represent means ± SD; *p<0.05 <i>vs</i> Control; §p<0.05 <i>vs</i> Diabetes, respectively; (bars show means±SD; n = 8–10/group). IOD – integrated optical density.</p

Confocal images of control, diabetic and treated diabetic rats.

<p>Aldosterone inhibitors prevented the mislocation of NKA induced by diabetes in proximal tubules. Representative pictures of immunofluorescence staining of kidney sections for Na/K ATPase (NKA, green) in control (A), streptozotocin-diabetic (B) and diabetic, Enalapril (C), Losartan (D), Spironolactone (E) and Eplerenone (F) treated rats (63x magnification; scale bar–10 μm). Nuclei are stained blue with Hoechst. PT-proximal tubule, DT-distal tubule, Bm-basal membrane, Lu – apical membrane at the lumen and Nucl – nuclei. Fluorescent signal intensity of NKA (green) generated from a line shown as red arrow in the merged image are shown on the bottom right of each panel.</p

Metabolic and renal parameters of control, diabetic and treated diabetic rats.

<p>Data are means ± SD, n = 8–10/group, ^*p<0.05 vs. C; ^§p<0.05 vs. D, ^**p<0.01 vs. C; ^§§p<0.01 vs. D, ^***p<0.001 vs. C; ^§§§p<0.001 vs. D; respectively. UD–undetectable.</p

Renal histopathology in control, diabetic and treated diabetic rats.

<p>Aldosterone antagonists were the most effective in attenuating the structural lesions of DN. Representative PAS staining of kidney sections (40x magnification; scale bar –50 μm): non-diabetic control (A), STZ-induced diabetic (B), Enalapril (E), Losartan (F), Spironolactone (G) and Eplerenone (H) treated diabetic rats (n = 8–10/group). Long, wide headed arrows point on mesangial matrix; long, narrow headed arrows on arterioles. Armanni-Ebstein lesions are marked with short, wide headed arrows. <i>C</i>: Mesangial fractional volume values (Vv) are defined by the ratio of mesangial area/glomerular tuft area. The mesangial area is determined by assessment of PAS-positive and nucleus-free areas in the mesangium. *p<0.05 <i>vs</i> Control; §p<0.05 <i>vs</i> Diabetes, respectively; (bars show means ± SD). <i>D</i>: Arteriolar hyalinosis is defined by the average of hyalinized quarters of arterioles. The hyalin is determined by assessment of PAS-positive and nucleus-free areas within the arterioles. *p<0.05 <i>vs</i> Control; §p<0.05 <i>vs</i> Diabetes, respectively; (bars show means ± SD).</p

Neurocognitive functions of pediatric kidney transplant recipients

BACKGROUND: End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited. METHODS: We conducted a cross-sectional analysis comparing cognitive functions (using the Woodcock-Johnson International Edition, WJIE) in 35 kidney transplant and 35 healthy control children. Data on laboratory measurements, comorbidities, and social characteristics were collected. RESULTS: Transplant children had significantly worse scores on the intelligence quotient (IQ) test compared with controls [Full Scale IQ score 85 (26) vs 107 (10), p 9 months) were associated with lower test scores. Age-standardized duration of hospitalization was inversely correlated with IQ (r = -0.46, p <0.01) and was an independent significant predictor (Beta = -0.38, p = 0.02) of IQ scores in transplanted children. CONCLUSIONS: Child kidney transplant recipients have neurocognitive function impairments that are associated with markers of socioeconomic status (SES) and factors related to disease severity

Agricultural economics and transition: What was expected, what we observed, the lessons learned Proceedings (Volume I / II)

Over fifteen years have elapsed since the transition from the centrally planned economic system started in the early 1990’s. During this time agricultural and rural areas of Central and Eastern Europe have undergone profound structural changes with wide variations in the degree of transformation and in the rate of success in creating a competitive market and private ownership based food and agricultural system. By becoming member of the European Union the "transition" in its traditional interpretation has been concluded in ten of the Central East European countries. The transition to market based agriculture, however, is far from completion in Southern and Eastern Europe and especially in the CIS countries. International Association of Agricultural Economists (IAAE) and European Association of Agricultural Economists (EAAE) in collaboration with the Corvinus University of Budapest and with a number of other institutions in Hungary organized an inter-conference seminar on the subject of agricultural transition in Central and Eastern Europe and Central Asia. The major objective of the seminar was to discuss and draw conclusions on the role of agricultural policy in the transition process in the light of actual progress and current situation in Central and East European countries and in formal Soviet States. In addition the contribution of agricultural economics – both from the West and from the East – as a discipline and a profession to the transition process in agriculture were discussed. A specific objective was to identify priorities and means to strengthen the agricultural economics profession in the transition countries and determine research and educational priorities for the future. The seminar was attended by 118 participants representing 26 countries from Europe, North America and Asia. The Seminar was the largest professional meeting organized by the two associations in 2007. Over 110 abstracts were submitted and evaluated by the International Program Committee. In the two day program of the meeting, 8 presentations were made during the 3 plenary sessions, 66 papers were presented in the 15 contributed paper sessions in 8 subject categories. In addition there were 15 posters discussed in the poster session and the findings of a World Bank study on distortions of agricultural incentives in the region was the subject of a pre-conference workshop. Plenary speakers included Ulrich Koester, Johan Swinnen, Jerzy Wilkin, Zvi Lerman, Eugenia Serova and József Popp-Gábor Udovecz. At the end of the seminar David Colman, President of IAAE gave a global assessment of the status of agricultural economics discipline and profession, while Csaba Csáki, former President of IAAE made summary comments on major issues discussed during the seminar. This volume includes the plenary and contributed papers presented at the seminar and submitted for publications by the authors as well as the abstracts of the poster papers discussed. The seminar was supported and sponsored by a number of organizations and persons. All of their contributions have to be greatly acknowledged. First the two international organizations IAAE and EAAE have to be mentioned, which provided overall organizational framework and logistical support. The IAAE provided in addition a generous grant to support the participation of young agricultural economists from Central and Eastern Europe on the seminar. On the Hungarian side the Corvinus University of Budapest, the Szent István University of Gödöllő, the Research Institute for Agricultural Economics, the Hungarian Agricultural Economics Association, the Hungarian Association of Agricultural Sciences and the Hungarian Ministry of Agriculture and Rural Development were the major material and organizational supporters. The International Program committee was chaired by David Colman and Csaba Csáki and included Ulrich Koester, Joe Swinnen, Eugenia Serova and Jerzy Wilkin. The local Organizing committee was chaired by Csaba Forgács and István Szűcs and included Zoltán Lakner, András Nábrádi, József Popp, József Tóth, Gábor Udovecz, László Vajda, László Villányi, Krisztina Fodor, Attila Jámbor and Tamás Mizik. Finally IAMO, Halle facilitated the publication of this proceedings