Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sympatho-excitation during chemoreflex active expiration is mediated by L-glutamate in the RVLM/Bötzinger complex of rats

The involvement of glutamatergic neurotransmission in the rostral ventrolateral medulla/Bötzinger/pre-Bötzinger complexes (RVLM/BötC/pre-BötC) on the respiratory modulation of sympathoexcitatory response to peripheral chemoreflex activation (chemoreflex) was evaluated in the working heart-brain stem preparation of juvenile rats. We identified different types of baro- and chemosensitive presympathetic and respiratory neurons intermingled within the RVLM/BötC/pre-BötC. Bilateral microinjections of kynurenic acid (KYN) into the rostral aspect of RVLM (RVLM/BötC) produced an additional increase in frequency of the phrenic nerve (PN: 0.38 ± 0.02 vs. 1 ± 0.08 Hz; P < 0.05; n = 18) and hypoglossal (HN) inspiratory response (41 ± 2 vs. 82 ± 2%; P < 0.05; n = 8), but decreased postinspiratory (35 ± 3 vs. 12 ± 2%; P < 0.05) and late-expiratory (24 ± 4 vs. 2 ±1%; P < 0.05; n = 5) abdominal (AbN) responses to chemoreflex. Likewise, expiratory vagal (cVN; 67 ± 6 vs. 40 ± 2%; P < 0.05; n = 5) and expiratory component of sympathoexcitatory (77 ± 8 vs. 26 ± 5%; P < 0.05; n = 18) responses to chemoreflex were reduced after KYN microinjections into RVLM/BötC. KYN microinjected into the caudal aspect of the RVLM (RVLM/pre-BötC; n = 16) abolished inspiratory responses [PN (n = 16) and HN (n = 6)], and no changes in magnitude of sympathoexcitatory (n = 16) and expiratory (AbN and cVN; n = 10) responses to chemoreflex, producing similar and phase-locked vagal, abdominal, and sympathetic responses. We conclude that in relation to chemoreflex activation 1) ionotropic glutamate receptors in RVLM/BötC and RVLM/pre-BötC are pivotal to expiratory and inspiratory responses, respectively; and 2) activation of ionotropic glutamate receptors in RVLM/BötC is essential to the coupling of active expiration and sympathoexcitatory response.

Dysautonomias in parkinson's disease: cardiovascular changes and autonomic modulation in conscious rats after infusion of bilateral 6-OHDA in substantia nigra

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)

Comparison of imaging methods for diagnosis of renal tumors and their calcifications

Background: To establish the best methodology for diagnosis and management of patients with solid and complex renal masses by comparing the costs and benefits of different imaging methods and to improve differential diagnosis of these benign and malignant lesions, particularly by investigating tumour calcifications. Methods: We performed a prospective study on 31 patients with solid or complex masses by submitting them to Abdominal Ultrasonography (US), Doppler Ultrasonography of the renal mass (US Dop), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI). Results: We found 28 patients with malignant and three with benign masses. Of the 28 malignant, 17 showed calcifications at CT; 16 central and one was of the pure peripheral curvilinear type (egg shell). Excretory Urography (IVP) had a significantly lower detection rate for central calcifications than both US and CT. Benign and malignant masses appeared as described in literature, with US, CT and MRI showing high sensitivity and specificity in renal tumor diagnosis. The exception was US Dop where we obtained lower sensitivity for the characterization of malignant tumor flow. Conclusions: In this series we were surprised to find that CT revealed central calcifications in 51.6% of patients, all with malignant lesions, while, literature reports a frequency of calcification in renal cell carcinoma between 8 and 22%, in studies using abdominal films and EU (IVP). This finding is of great importance when we consider that these calcifications occur particularly in malignant neoplasms. As a result of comparing these different imaging methods we have developed a better methodology for renal tumor investigation.

Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

Background: Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34(+) hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters. Results: By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34(+) cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34(+) cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro-apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly. Conclusions: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.

Mechanisms of blunted muscle vasodilation during peripheral chemoreceptor stimulation in heart failure patients

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O-2 and 90% N-2). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N-G-monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012; 60: 669-676.) . Online Data Supplement

Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy

Abstract Background The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system. Methods Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg-1). Animals were sacrificed seven days later. Results Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction. Conclusion FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.

Body weight, metabolism and clock genes

Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity.

Stratigraphy and Palaeontology of the Late Cretaceous Wapiti Formation, west-central Alberta, Canada

A complete stratigraphic assessment and revision of the middle Campanian to upper Maastrichtian Wapiti Formation in north-western Alberta and north-eastern British Columbia is the main aim of this research project. The study area encompasses an area of approximately 200X180 km in the Grande Prairie County (west-central Alberta) and easternmost British Columbia, Canada. Results presented here indicate that the 1300m thick succession currently reported in the literature as “undifferentiated lithostratigraphic unit”, consists of five lithostratigraphic units and four unconformity-bounded depositional sequences; their study and description have been documented integrating several geological disciplines, including sequence stratigraphic methods, well-log signatures, facies analysis, and fossil associations. On the whole, particular attention has been given to 1) age and nature of both basal and upper contacts of the Wapiti Formation, 2) effective mappability of lithostratigraphic units and depositional sequences in western Alberta, and 3) the identification of previously undetermined maximum flooding surface of the Bearpaw seaway and Drumheller Marine Tongue, which are reference marine unit in central and southern Alberta. A second, but not less important, guideline for the project has been the rich paleontological record of the Wapiti deposits. Detailed paleoenvironmental and taxonomical information on old and new finds have been the base for correlation with well known associations of Alaska, southern Alberta, and Montana. Newly discovered rich fossil localities documented an extraordinarily diverse fauna during the latest Cretaceous, including dinosaurs, squamates, and fresh-water fishes and reptiles. Lastly, in order to better characterize the Wapiti Formation, major marker beds were described: these include several bentonites (altered volcanic ash deposits) which have been documented over an area of almost 30.000 km2, as well as four major coal zones, characterized by tabular coal seams with an overall thickness of 2 meters. Such marker beds represent a formidable tool for high-resolution chronology and regional correlations within the Late Cretaceous Alberta foreland basin.

Geochronological and structural evolution of the western and central Kaoko Belt in NW Namibia

This thesis focusses on the tectonic evolution and geochronology of part of the Kaoko orogen, which is part of a network of Pan-African orogenic belts in NW Namibia. By combining geochemical, isotopic and structural analysis, the aim was to gain more information about how and when the Kaoko Belt formed. The first chapter gives a general overview of the studied area and the second one describes the basis of the Electron Probe Microanalysis dating method. The reworking of Palaeo- to Mesoproterozoic basement during the Pan-African orogeny as part of the assembly of West Gondwana is discussed in Chapter 3. In the study area, high-grade rocks occupy a large area, and the belt is marked by several large-scale structural discontinuities. The two major discontinuities, the Sesfontein Thrust (ST) and the Puros Shear Zone (PSZ), subdivide the orogen into three tectonic units: the Eastern Kaoko Zone (EKZ), the Central Kaoko Zone (CKZ) and the Western Kaoko Zone (WKZ). An important lineament, the Village Mylonite Zone (VMZ), has been identified in the WKZ. Since plutonic rocks play an important role in understanding the evolution of a mountain belt, zircons from granitoid gneisses were dated by conventional U-Pb, SHRIMP and Pb-Pb techniques to identify different age provinces. Four different age provinces were recognized within the Central and Western part of the belt, which occur in different structural positions. The VMZ seems to mark the limit between Pan-African granitic rocks east of the lineament and Palaeo- to Mesoproterozoic basement to the west. In Chapter 4 the tectonic processes are discussed that led to the Neoproterozoic architecture of the orogen. The data suggest that the Kaoko Belt experienced three main phases of deformation, D1-D3, during the Pan-African orogeny. Early structures in the central part of the study area indicate that the initial stage of collision was governed by underthrusting of the medium-grade Central Kaoko zone below the high-grade Western Kaoko zone, resulting in the development of an inverted metamorphic gradient. The early structures were overprinted by a second phase D2, which was associated with the development of the PSZ and extensive partial melting and intrusion of ~550 Ma granitic bodies in the high-grade WKZ. Transcurrent deformation continued during cooling of the entire belt, giving rise to the localized low-temperature VMZ that separates a segment of elevated Mesoproterozoic basement from the rest of the Western zone in which only Pan-African ages have so far been observed. The data suggest that the boundary between the Western and Central Kaoko zones represents a modified thrust zone, controlling the tectonic evolution of the Kaoko belt. The geodynamic evolution and the processes that generated this belt system are discussed in Chapter 5. Nd mean crustal residence ages of granitoid rocks permit subdivision of the belt into four provinces. Province I is characterised by mean crustal residence ages <1.7 Ga and is restricted to the Neoproterozoic granitoids. A wide range of initial Sr isotopic values (87Sr/86Sri = 0.7075 to 0.7225) suggests heterogeneous sources for these granitoids. The second province consists of Mesoproterozoic (1516-1448 Ma) and late Palaeo-proterozoic (1776-1701 Ma) rocks and is probably related to the Eburnian cycle with Nd model ages of 1.8-2.2 Ga. The eNd i values of these granitoids are around zero and suggest a predominantly juvenile source. Late Archaean and middle Palaeoproterozoic rocks with model ages of 2.5 to 2.8 Ga make up Province III in the central part of the belt and are distinct from two early Proterozoic samples taken near the PSZ which show even older TDM ages of ~3.3 Ga (Province IV). There is no clear geological evidence for the involvement of oceanic lithosphere in the formation of the Kaoko-Dom Feliciano orogen. Chapter 6 presents the results of isotopic analyses of garnet porphyroblasts from high-grade meta-igneous and metasedimentary rocks of the sillimanite-K-feldspar zone. Minimum P-T conditions for peak metamorphism were calculated at 731±10 °C at 6.7±1.2 kbar, substantially lower than those previously reported. A Sm-Nd garnet-whole rock errorchron obtained on a single meta-igneous rock yielded an unexpectedly old age of 692±13 Ma, which is interpreted as an inherited metamorphic age reflecting an early Pan-African granulite-facies event. The dated garnets survived a younger high-grade metamorphism that occurred between ca. 570 and 520 Ma and apparently maintained their old Sm-Nd isotopic systematics, implying that the closure temperature for garnet in this sample was higher than 730 °C. The metamorphic peak of the younger event was dated by electronmicroprobe on monazite at 567±5 Ma. From a regional viewpoint, it is possible that these granulites of igneous origin may be unrelated to the early Pan-African metamorphic evolution of the Kaoko Belt and may represent a previously unrecognised exotic terrane.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

Central Europeans towards Integration with the European Union: A Study of Public Opinion, Social Attitudes and National Identities

Since the turbulence of 1989, the countries of Central and Eastern Europe have striven to "return to Europe". Agreements have been signed with ten post-communist countries, beginning in 1991 with Czechoslovakia (before its division), Hungary and Poland. Since that time several countries have expressed a desire to become members of the EU. In 1997 the European Commission announced its opinion on the applications for EU membership of the Czech Republic, Hungary, Poland, Slovakia, and seven other applicant countries. The Commission recommended the commencement of negotiations on accession with the Czech Republic, Estonia, Hungary, Poland, and Slovenia. Mr. Kucia's report, presented in the form of a series of manuscripts totalling 91 pages, written in English and Polish and including many pages of tables and graphs, presents the results of a study of public opinion on European integration in four countries of Central Europe (CE): the Czech Republic (CZ), Hungary (H), Poland (PL), and Slovakia (SK). The research results are primarily based on a public-opinion survey known as the Central and Eastern Eurobarometer (CEEB). CEEB has been conducted on behalf of the European Commission in the Central and Eastern European countries each year in autumn since 1990. Below is a very small selection of Mr. Kucia's research findings. Throughout the 90s people in the four countries increasingly saw their countries' future tied up with the EU, since economic and political connections to the EU were growing and prospects for EU membership were increasing. Regional co-operation within CE did not gain much popular recognition. However, initially high levels of enthusiasm for the EU were gradually superseded by a more realistic approach or even scepticism. Poland was the exception in this respect; its population was more positive about the EU in 1996 than ever before. Mr. Kucia concludes that, since the political "elites" in CE are more positive about the EU than the people they serve, they should do their best to bring people round to their beliefs, lest the project of European integration become purely the business of the elites, as Mr. Kucia claims it has been in the EU up till now. He accuses the governments of the region, the EU authorities and the media of failing to provide appropriate information, especially about the two subjects which most affect them, association with the EU and the PHARE assistance programme. Respondents were asked to rank in order the countries or regions they saw their country's future most closely tied up with. In the period 92-96 the EU received the highest ratings in all of CE. The ratings were highest in CZ in 92 and 93 (46%) and in Poland in 96 (46%). They were the lowest in Hungary (22% in 94). After the EU came "Other Western European countries (non EU)", that is Austria, Sweden and Finland (before they joined the EU in 1995), Switzerland and Norway. Mr. Kucia puts the high ratings of these countries down to historical connections and geographical proximity, particularly in the case of Austria. The USA always came second in Poland, and in Hungary too its standing has always been higher than in CZ or SK. Indeed Mr. Kucia suggests that the USA's standing is disproportionately low in especially the CZ. Germany was nominated frequently by Hungarians, though in the CZ and SK, figures have been consistently low (1-2%). "Other CE/EE countries" increased their ratings in all of CE except Poland between 92 and 96. With regard to these last figures, Mr. Kucia makes an interesting note. Assuming that for the respondents in the four countries this category covered the Visegrad 4, least support was found in Poland, whose government was the most in favour of close political co-operation within the V4, while most support was in evidence in CZ and SK, for whose governments V4 was simply not a priority. Again, there is evidence of a divide between the political elites and the people. Russia has occupied a consistently modest rank. It was the highest in PL, fairly low in H and SK and the lowest in CZ. The Slovak government's policy of closer ties with Russia is reflected in a growth in the figures from 2% in 93 to 6% in 95. Every year the spontaneous answer "we should depend on ourselves" appeared, which Mr. Kucia interprets as either a sign of isolationism and disillusionment or as a call for self-reliance. Unfortunately he regards both these tendencies as unfeasible in the uniting Europe. Moving to more general conclusions, Mr. Kucia finds that the concept "Central Europe" does not have much meaning for Central Europeans. He believes that this is probably due to the failure to establish a viable regional co-operation network. Group discussions also revealed that people thought themselves European as a consequence of being Czech or Polish etc. Thus European identity is based on national identities. Generally within the surveyed period, the numbers of those who said they often think themselves European decreased, while the numbers of those who said they never think themselves European increased from 41% in PL, 36% in CZ, and 30% in H in 1990, to 67% in CZ, 58% in PL, and 51% in H in 1995.

Central Europe in the Process of European Integration. A Comparative Study of the Strategies of the Czech Republic, Hungary, Poland and Slovakia towards the Deepening and Widening of the European Union

Membership of the European Union U is usually seen as a strategic goal of the associated states of central and eastern Europe. At the beginning of the 1990s central European countries, where the economic and political transformation was relatively advanced, received preferential treatment from the European Community, which was starting to evolve a policy of differentiation. Podraza studied the strategies of four central European countries towards changes under way in the European Union, analysing several aspects for each case: (1) the process of political transformation (2) decision-making structures in the field of foreign policy and European integration (3) integration strategies: (a) main foreign policy priorities (b) application for membership of the European Union (c) the Commission option on each country (d) accession partnership, including a National Programme for the Adoption of the Acquis (NPAA) (e) regular Commission reports (f) accession negotiations

Corticospinal output and loss of force during motor fatigue

The objective of this study was to analyze central motor output changes in relation to contraction force during motor fatigue. The triple stimulation technique (TST, Magistris et al. in Brain 121(Pt 3):437-450, 1998) was used to quantify a central conduction index (CCI = amplitude ratio of central conduction response and peripheral nerve response, obtained simultaneously by the TST). The CCI removes effects of peripheral fatigue from the quantification. It allows a quantification of the percentage of the entire target muscle motor unit pool driven to discharge by a transcranial magnetic stimulus. Subjects (n = 23) performed repetitive maximal voluntary contractions (MVC) of abductor digiti minimi (duration 1 s, frequency 0.5 Hz) during 2 min. TST recordings were obtained every 15 s, using stimulation intensities sufficient to stimulate all cortical motor neurons (MNs) leading to the target muscle, and during voluntary contractions of 20% of the MVC to facilitate the responses. TST was also repetitively recorded during recovery. This basic exercise protocol was modified in a number of experiments to further characterize influences on CCI of motor fatigue (4 min exercise at 50% MVC; delayed fatigue recovery during local hemostasis, "stimulated exercise" by 20 Hz trains of 1 s duration at 0.5 Hz during 2 min). In addition, the cortical silent period was measured during the basic exercise protocol. Force fatigued to approximately 40% of MVC in all experiments and in all subjects. In all subjects, CCI decreased during exercise, but this decrease varied markedly between subjects. On average, CCI reductions preceded force reductions during exercise, and CCI recovery preceded force recovery. Exercising at 50% for 4 min reduced muscle force more markedly than CCI. Hemostasis induced by a cuff delayed muscle force recovery, but not CCI recovery. Stimulated exercise reduced force markedly, but CCI decreased only marginally. Summarized, force reduction and reduction of the CCI related poorly quantitatively and in time, and voluntary drive was particularly critical to reduce the CCI. The fatigue induced reduction of CCI may result from a central inhibitory phenomenon. Voluntary muscle activation is critical for the CCI reduction, suggesting a primarily supraspinal mechanism.

Citrate- vs. acetate-based dialysate in bicarbonate haemodialysis: consequences on haemodynamics, coagulation, acid-base status, and electrolytes

BACKGROUND: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency. METHODS: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers. RESULTS: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate. CONCLUSION: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.