Electrical colonic stimulation reduces mean transit time in a porcine model.

Abstract Electrical stimulation is a new way to treat digestive disorders such as constipation. Colonic propulsive activity can be triggered by battery operated devices. This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic examination of the caecum was routinely performed after animal sacrifice. A reduction of mean transit time was observed after electrical stimulation (19 +/- 13 h; mean +/- SD) when compared to reference (34 +/- 7 h; P = 0.045) and mean transit time after sham stimulation (36 +/- 9 h; P = 0.035). Histological examination revealed minimal chronic inflammation around the electrodes. Colonic transit time measured in a chronic porcine model is reduced by direct sequential electrical stimulation. Minimal tissue lesion is elicited by stimulation or implanted material. Electrical colonic stimulation could be a promising approach to treat specific disorders of the large bowel.

Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: a study in GLUT2-null mice.

The physiological significance of the presence of GLUT2 at the food-facing pole of intestinal cells is addressed by a study of fructose absorption in GLUT2-null and control mice submitted to different sugar diets. Confocal microscopy localization, protein and mRNA abundance, as well as tissue and membrane vesicle uptakes of fructose were assayed. GLUT2 was located in the basolateral membrane of mice fed a meal devoid of sugar or containing complex carbohydrates. In addition, the ingestion of a simple sugar meal promoted the massive recruitment of GLUT2 to the food-facing membrane. Fructose uptake in brush-border membrane vesicles from GLUT2-null mice was half that of wild-type mice and was similar to the cytochalasin B-insensitive component, i.e. GLUT5-mediated uptake. A 5 day consumption of sugar-rich diets increased fructose uptake fivefold in wild-type tissue rings when it only doubled in GLUT2-null tissue. GLUT5 was estimated to contribute to 100 % of total uptake in wild-type mice fed low-sugar diets, falling to 60 and 40 % with glucose and fructose diets respectively; the complement was ensured by GLUT2 activity. The results indicate that basal sugar uptake is mediated by the resident food-facing SGLT1 and GLUT5 transporters, whose mRNA abundances double in long-term dietary adaptation. We also observe that a large improvement of intestinal absorption is promoted by the transient recruitment of food-facing GLUT2, induced by the ingestion of a simple-sugar meal. Thus, GLUT2 and GLUT5 could exert complementary roles in adapting the absorption capacity of the intestine to occasional or repeated loads of dietary sugars.

Soil Aggregation, Organic Carbon Concentration, and Soil Bulk Density As Affected by Cover Crop Species in a No-Tillage System

Soil aggregation and the distribution of total organic carbon (TOC) may be affected by soil tillage and cover crops. The objective of this study was to determine the effects of crop rotation with cover crops on soil aggregation, TOC concentration in the soil aggregate fractions, and soil bulk density under a no-tillage system (NTS) and conventional tillage system (CTS, one plowing and two disking). This was a three-year study with cover crop/rice/cover crop/rice rotations in the Brazilian Cerrado. A randomized block experimental design with six treatments and three replications was used. The cover crops (treatments) were: fallow, Panicum maximum, Brachiaria ruziziensis, Brachiaria brizantha, and millet (Pennisetum glaucum). An additional treatment, fallow plus CTS, was included as a control. Soil samples were collected at the depths of 0.00-0.05 m, 0.05-0.10 m, and 0.10-0.20 m after the second rice harvest. The treatments under the NTS led to greater stability in the soil aggregates (ranging from 86.33 to 95.37 %) than fallow plus CTS (ranging from 74.62 to 85.94 %). Fallow plus CTS showed the highest number of aggregates smaller than 2 mm. The cover crops affected soil bulk density differently, and the millet treatment in the NTS had the lowest values. The cover crops without incorporation provided the greatest accumulation of TOC in the soil surface layers. The TOC concentration was positively correlated with the aggregate stability index in all layers and negatively correlated with bulk density in the 0.00-0.10 m layer.

Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson disease.

STUDY OBJECTIVE: A preliminary study by our group suggested an association between daytime sleepiness and the catechol-O-methyltransferase (COMT) val158met polymorphism (rs4680) in patients with Parkinson disease (PD). We sought to confirm this association in a large group of patients with PD. DESIGN: Genetic association study in patients with PD. SETTING: Movement disorder sections at 2 university hospitals. PARTICIPANTS: PD patients with and without episodes of suddenly falling asleep matched for antiparkinsonian medication, disease duration, sex, and age, who participated in a previous genetic study on dopamine-receptor polymorphisms. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: In this study, 240 patients with PD (154 men; age 65.1 +/- 6.1 years; disease duration 9.4 +/- 6.0 years) were included. Seventy had the met-met (LL), 116 the met-val (LH), and 54 the val-val (HH) genotype. In the combined LL+LH group (featuring reduced COMT activity), the mean Epworth Sleepiness Scale (ESS) score was 9.0 +/- 5.9 versus 11.0 +/- 6.1 in the HH (high COMT activity) group (P = .047). Forty-seven percent of the LL and LH patients had sudden sleep onset compared with 61% of the HH patients (P = .07). Logistic regression, however, showed that both pathologic ESS scores (i.e., > 10) and sudden sleep onset were predicted by subjective disease severity (P < .001 each) but not by the COMT genotype. CONCLUSIONS: Our previous finding that the L-allele may be associated with daytime sleepiness could not be confirmed in the present study. Altogether, our data do not support a clinically relevant effect of the COMT genotype on daytime sleepiness in PD.

Les variations du développement sexuel: «La différence au grand jour»

Contexte : Hermaphrodisme, pseudohermaphrodisme, intersexe ou encore troubles du développement du sexe (Disorders of Sex Development) : autant de termes désignant des pathologies concernant une proportion non-négligeable de la population. Dans une société où le développement génital et l'identité sexuelle sont à la fois tabous et mal connus, le corps médical a un rôle clé à jouer dans la prise en charge à long terme ainsi que dans le soutien des patients intersexués et de leur entourage proche. Cette prise en charge commence par une information complète et transparente des parents et des enfants touchés. Objectifs : Elaborer un document capable de décrire de la manière la plus complète et compréhensible possible le thème de l'intersexualité. Il sera à la fois basé sur les connaissances médicales actuelles, mais également sur les témoignages de patients, parents et groupes de soutien aux intersexes. Il sera finalement destiné à l'information des parents ainsi que de leurs enfants intersexués à différentes étapes de leur développement. Méthode : Une compréhension approfondie de la thématique de l'intersexualité sur le plan médical, impliquant une approche multidisciplinaire, est une première étape cruciale. Agrémentée de témoignages de patients, de parents et des divers groupes de soutient actifs sur ce sujet, nous obtiendrons les bases nécessaires pour concevoir un document d'information à la fois le plus complet et le plus proche possible des attentes des patients et des parents. Résultat escompté : Répondre aux attentes formulées par les différents acteurs de la thématique de l'intersexualité et ainsi promouvoir une meilleure compréhension des mécanismes et des enjeux qui la caractérisent. Obtenir un feedback positif des groupes de soutien aux intersexes sur la qualité de l'information donnée dans ce document.

PGC-1α induces mitochondrial and myokine transcriptional programs and lipid droplet and glycogen accumulation in cultured human skeletal muscle cells

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a chief activator of mitochondrial and metabolic programs and protects against atrophy in skeletal muscle (skm). Here we tested whether PGC-1α overexpression could restructure the transcriptome and metabolism of primary cultured human skm cells, which display a phenotype that resembles the atrophic phenotype. An oligonucleotide microarray analysis was used to reveal the effects of PGC-1α on the whole transcriptome. Fifty-three different genes showed altered expression in response to PGC-1α: 42 upregulated and 11 downregulated. The main gene ontologies (GO) associated with the upregulated genes were mitochondrial components and processes and this was linked with an increase in COX activity, an indicator of mitochondrial content. Furthermore, PGC-1α enhanced mitochondrial oxidation of palmitate and lactate to CO2, but not glucose oxidation. The other most significantly associated GOs for the upregulated genes were chemotaxis and cytokine activity, and several cytokines, including IL-8/CXCL8, CXCL6, CCL5 and CCL8, were within the most highly induced genes. Indeed, PGC-1α highly increased IL-8 cell protein content. The most upregulated gene was PVALB, which is related to calcium signaling. Potential metabolic regulators of fatty acid and glucose storage were among mainly regulated genes. The mRNA and protein level of FITM1/FIT1, which enhances the formation of lipid droplets, was raised by PGC-1α, while in oleate-incubated cells PGC-1α increased the number of smaller lipid droplets and modestly triglyceride levels, compared to controls. CALM1, the calcium-modulated δ subunit of phosphorylase kinase, was downregulated by PGC-1α, while glycogen phosphorylase was inactivated and glycogen storage was increased by PGC-1α. In conclusion, of the metabolic transcriptome deficiencies of cultured skm cells, PGC-1α rescued the expression of genes encoding mitochondrial proteins and FITM1. Several myokine genes, including IL-8 and CCL5, which are known to be constitutively expressed in human skm cells, were induced by PGC-1α.

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development.

Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.

Simple holographic polarogram

A new technique capable of obtaining quantitative values of the rotation angle of the polarization vector by using holography is presented. This is a two-stage holographic process; during the recording stage a hologram of the object of interest is obtained. The reference beam is composed of two beams that form a small angle between them and keep their polarization states at right angles to each other. In the reconstruction stage of the hologram, two images from the hologram are obtained along two different angles. As a result of the interference between these two images, a set of parallel fringes is formed at the image plane. The fringe contrast on the reconstruction is related to the angle of the polarization vector of the light at each position on the image plane. Measurements of the rotation of the polarization angle of a fraction of a degree were obtained. The main application of this technique is in the study of transient phenomena, where single-shot measurements are the only means of obtaining reliable data.

Cytotoxic T-cell and NK-cell Lymphomas: Current Questions and Controversies.

The cytotoxic T-cell and natural killer (NK)-cell lymphomas and related disorders are important but relatively rare lymphoid neoplasms that frequently are a challenge for practicing pathologists. This selective review, based on a meeting of the International Lymphoma Study Group, briefly reviews T-cell and NK-cell development and addresses questions related to the importance of precise cell lineage (αβ-type T cell, γδ T cell, or NK cell), the implications of Epstein-Barr virus infection, the significance of anatomic location including nodal disease, and the question of further categorization of enteropathy-associated T-cell lymphomas. Finally, developments subsequent to the 2008 World Health Organization Classification, including the recognition of indolent NK-cell and T-cell disorders of the gastrointestinal tract are presented.

Investigation phytochimique d'une plante médicinale malgache Hypoestes serpens (Vahl) R. Br. (Acanthaceae) variété glabre et étude comparative avec la variété poilue

Résumé A Madagascar, comme dans plusieurs pays en développement, une grande partie de la population utilise les plantes pour se soigner. Plusieurs espèces des plantes sont ainsi utilisées en médecine traditionnelle malgache. Par ailleurs, la plupart de ces plantes ne font l'objet que de très peu d'étude scientifique. En effet, dans le cadre de l'investigation phytochimique de plantes utilisées en médecine traditionnelle malgache et dans la recherche des nouvelles substances biologiquement actives, Hypoestes serpens (Vahl) R. Br. (Acanthaceae) a été étudiée. Elle se présente sous deux variétés (glabre et poilue) qui sont tous utilisées dans la région sud-centre de Madagascar pour traiter la blennorragie. De l'extrait dichlorométhanique des feuilles de H. serpens (Vahl) R. Br. variété glabre, 12 diterpénoides dont 8 nouveaux ont été isolés. Ils ont tous montré une activité antifongique contre un champignon pathogène des plantes, Cladosporium cucumerinum, dans la bioautographie directe sur CCM. Quelques-uns ont également présenté une activité contre une levure saprophyte chez l'homme, Candida albicans et une activité inhibitrice de l'enzyme acétylcholinesterase. Les diterpènoïdes sont déjà considérés comme les principaux métabolites secondaires du genre Hypoestes. Le fractionnement de l'extrait méthanolique a conduit à l'isolement de 5 glycosides des flavonoïdes dont 4 sous formes C-g,lycosides qui n'ont jamais été identifiés dans la famille Acanthaceae. Ces flavonoïdes ont présenté une activité antiradicalaire contre le DPPH. Le fractionnement et la purification des extraits ont été effectués à l'aide des différentes techniques chromatographiques telles que la chromatographie sur colonne ouverte, la filtration sur gel, la chromatographie liquide à haute pression, la chromatographie liquide à moyenne pression et la chromatographie liquide à basse pression. Par ailleurs, les structures des composés isolés ont été élucidées par des techniques spectroscopiques (UV, MS, RMN) et de méthode chimique (hydrolyse acide). En plus de ces techniques, certaines méthodes physiques (cristallographie par rayons-X, mesure de rotation optique) ont été réalisées pour confirmer certaines structures. Comme l'espèce Hypoestes serpens (Vahl) R. Br. se présente en deux variétés, une étude comparative a été effectuée. Cette étude avait montré que ces deux variétés ont une activité biologique similaire. Finalement, une technique analytique couplée, HPLC-UV-APC1-MS a permis de montrer la présence de toutes les substances isolées de la variété glabre dans la variété poilue. Second résumé Depuis des milliers d'almées, l'homme utilise les plantes pour se soigner. De nos jours, même avec le développement de la médecine moderne, la phytothérapie reste toujours la forme des soins de santé abordable et accessible pour la majorité des populations rurales des pays en développement. En outre, les plantes médicinales constituent une source potentielle de molécules biologiquement actives pour les industries pharmaceutiques et actuellement, on estime que 25% des médicaments commercialisés dans le monde sont à base de plantes Dans le cadre de la recherche des nouvelles molécules à intérêt thérapeutique qui pourraient devenir un médicament ou un modèle de structure ("lead compound") pour le développement de nouveaux médicaments, nous avons fait une étude sur l'espèce, Hypoestes serpens (Vahl) R. Br, plante utilisée en médecine traditionnelle malgache. Cette espèce existe en deux variétés, une glabre et une autre poilue qui sont tous utilisées dans la région sud-centre de Madagascar pour traiter la blennorragie. Par ailleurs, les tradipraticiens utilisent de préférence la variété poilue. Dans la première partie de ce présent travail, une investigation phytochimique de H serpens, variété glabre (variété moins utilisée) a d'abord été effectuée afm d'isoler et d'identifier le maximum des molécules biologiquement actives qu'elle contient. De ce fait, 17 composés dont 8 nouveaux ont été isolés. Les potentiels d'activités thérapeutiques des substances isolées ont ensuite été dépistés sur les différents cibles suivants.: deux souches de champignons (Cladosporium cucumerinum et Candida albicans), l'enzyme acétylcholinesterase et le radical DPPH. La deuxième partie de ce travail a été consacrée sur l'étude comparative des deux variétés (glabre et poilue) de H. serpens à la fois sur le plan biologique et sur le plan phytochimique. A l'issue de cette comparaison, nous avons constaté que l'utilisation de ces deux variétés en médecine traditionnelle malgache n'est pas un hasard ; les deux variétés avaient présenté une activité biologique très remarquable et contiennent les mêmes substances actives. Ces résultats démontrent les potentiels thérapeutiques de H serpens en médecine traditionnelle malgache et pourraient également encourager les tradipraticiens à utiliser la variété glabre tout en protégeant la variété poilue qui est en voie de disparition actuellement. En bref, l'investigation phytochimique de H. serpens justifiée par l'isolement et l'identification de certains de ses principes actifs ouvre la voie aux recherches des médicaments d'origine naturelle. Abstract In Madagascar, as in many developing countries, most people use plants to cure. A large number of plant species are employed in Malagasy traditional medicine. Moreover, most of these plants have been subject only very little scientific study. As part of a phytochemical investigation of plants used in Malagasy traditional medicine and in the search for new biologically active substances, Hypoestes serpens (Vah1) R.Br. (Acanthaceae) was investigated. This species exists in two varieties (glabrous and hairy) which are used in the south-center part of Madagascar to treat gonorrhoea. From the dichloromethane extract of the leaves of H. serpens (Vah1) R. Br. glabrous variety, 12 diterpenoids 8 of which were new, were isolated. They showed antifungal activity against the plant pathogen Cladosporium cucumerinum, in the direct TLC bioautography. Some of them also had activity against the yeast Candida athicans and inhibited acetylcholinesterase. The diterpenes are considered as the principal secondary metabolites of the genus Hypoestes. Fractionation of the methanol extract led to the isolation of 5 flavonoid glycosides, 4 of which were C-glycosides, never before identified in the Acanthaceae family. These flavonoids showed radical scavenging activity against DPPH. The fractionation and the purification of the extracts were achieved by different chromatographic techniques such as open-column chromatography, gel filtration, high- pressure liquid chromatography, medium-pressure liquid chromatography and low-pressure liquid chromatography. Moreover, the structures of the isolated compounds were elucidated by spectroscopic techniques (UV, MS, NMR) and chemical technique (acid hydrolysis). In addition, some physical methods (X-ray crystallography, measurement of optical rotation) were performed to confirm some structures. As the species Hypoestes serpens (Vah1) R. Br. is present in two varieties, a comparative study was carried out. This study showed that these two varieties had similar biological activity. Finally, a coupled analytical technique HPLC-UV-APCI-MS showed the presence of the same compounds in both the glabrous and hairy varieties.

Earthworm assemblages in an ecotone between forest and arable field and their relations with soil properties

The objective of this work was to assess the effects of a forest-field ecotone on earthworm assemblages. Five sites (blocks) differing in the type of crop rotation used in the field were studied in Central Bohemia, Czech Republic. In each block, sampling was carried out in seven parallel rows perpendicular to a transect from a forest (oak or oak-pine) to the centre of a field, both in spring and autumn 2001-2003. Individual rows were located in the forest (5 m from the edge), in the forest edge, and in the field (at 5, 10, 25, 50 and 100 m distances from the forest edge). The density and biomass of earthworms were lowest in the forest, increased markedly in the forest edge, decreased again at 5 or 10 m distance from the forest edge and then continuously increased along the distance to the field boundary. The highest number of species was found in the forest edge and in the field boundary. Individual species differed in their distribution along the transect. Both density and biomass of earthworms were correlated with distance from forest edge, soil organic matter content, soil porosity, and water infiltration rate.

Evolving techniques to evaluate ejaculatory function.

PURPOSE OF REVIEW: Recent findings in the physiology and neurobiology of ejaculation have expanded our understanding of male sexual function and have allowed the development of new instruments to investigate ejaculatory and orgasmic disorders. RECENT FINDINGS: The evidence-based definition of lifelong premature ejaculation has set a model in the evaluation and treatment outcome of sexual dysfunction. New instruments to objectively assess arousal, orgasm and the expulsion phase of ejaculation such as functional MRI, dynamic pelvic ultrasound, PET scans and validated questionnaires have lead to a better understanding of sexual dysfunction in men. Animal models, developments in neurobiology and clinical experience have transformed a purely psychoanalytical approach to ejaculatory and orgasmic function into a novel multidisciplinary, scientifically sound and evidence-based discipline of medicine. SUMMARY: Ejaculation is an integral part of normal sexual function. Ejaculatory dysfunction is common and may cause substantial disruption to the quality of a patient's life. A better understanding of the epidemiology, pathophysiology, neuroscience and genetics of ejaculatory and orgasmic function will eventually lead to the development of new, effective methods of treatment of disorders of ejaculation and orgasm in men.

Tukki- ja parruoptimoinnintoimivuuden kehittäminen

Diplomityön tutkimusfunktio käsittelee toimeksiantajan, Stora Enso Timber Oy Ltd Kotkan sahan, sahalinjan optimointikokonaisuuden relevanttia ongelmakenttää. Tutkimuksen alussa profiloivan sahalinjan tukinpyörityksen, pelkan sivuttaissiirron tai sivulautaoptimoinnin toimivuudesta ei ollut varmuutta. Työn painopistealue on sivulautaoptimointi, jonka toimivuus tutkimuksen alussa on hyvin kyseenalaista tuotantoajossa. Työn tavoitteet kiteytyvät paremman raaka-aineen käyttösuhteen saavuttamiselle, jolloin pitkän aikajänteen kannattavuus on realistisempaa saavuttaa. Kotkan sahalinjan optimointijärjestelmässä on kokonaisuudessaan saavutettu tuotantoajoon hyväksyttävä taso. Tukinpyörityksen tarkkuudessa saavutettiin asetettu tavoite, eli 90 % pyöritystuloksista menee virheikkunaan ± 10° , sekä virheen keskiarvon itseisarvo jasen ympärillä olevan hajonnan summa on maksimissaan 10° . Pelkan sivuttaissiirto todettiin tutkimuksessa sekundääriseksi optimointijärjestelmäksi. Ohjaus perustuu tukkimittarin mittaamaan dataan, jolloin tukinpyörityksen hajonta aiheuttaa epätarkkuutta pelkan suuntauksessa. Pelkan sivuttaisiirron käyttäminen vaatii lisämittauksia, jolloin voidaan varmistua pelkan suuntauksen optimoinnin toimivuudesta. Sivulautaoptimoinnin toimivuuden kehittämisessä saavutettiin se taso, missä todellista kehitystyötä voidaan tehdä. Koeajoissa ja optimointiohjelman tarkastamisessa havaittiin periaatteellisia virheitä, jotka korjattiin. Toimivan sivulautaoptimoinnin myötä on mahdollista hallita paremmin tuotannonohjaus, jolloin tuotanto voidaan etenkin sivulautojen osalta kohdentaa paremmin vastaamaan kysyntää sekä asete-erän hyvää käyttösuhdetta. Raaka-aineen käyttösuhde on parantunut. Yksittäisten asetevertailujen sekä esimerkkilaskelmien perusteella tuottopotentiaali tukinpyörityksen ja sivulautaoptimoinnin osalta on 0,6...1,5 MEUR Välillinen tuottopotentiaali on suurempi, koska tuotantoprosessi sahauksen osalta on erittäin joustava markkinoiden tarpeen muutoksille. Sahalinjalla on mahdollista tuottaa helposti laajalla tukkisumalla laajaa tuotematriisia, jossa sivulautaoptimoinnilla on avainrooli. Tuotannonsuunnittelufunktiota tulee kehittää vastaamaan mahdollisuuksiin,joita sivulautaoptimointi tarjoaa. Tuotematriisi ja sitä vastaavat asetteet lankeavalla tukkisumalla tulee rakentaa uudestaan niiltä osin, joihin sivulautaoptimointi antaa variaatiomahdollisuuksia.

Brain perfusion in sepsis.

Brain dysfunction is a frequent complication of sepsis, usually defined as "sepsis-associated encephalopathy" (SAE). Its pathophysiology is complex and related to numerous processes and pathways, while the exact mechanisms producing neurological impairment in septic patients remain incompletely elucidated. Alterations of the cerebral blood flow (CBF) may represent a key component for the development of SAE. Reduction of CBF may be caused by cerebral vasoconstriction, either induced by inflammation or hypocapnia. Endothelial dysfunction associated with sepsis leads to impairment of microcirculation and cerebral metabolic uncoupling that may further reduce brain perfusion so that CBF becomes inadequate to satisfy brain cellular needs. The natural autoregulatory mechanisms that protect the brain from reduced/ inadequate CBF can be impaired in septic patients, especially in those with shock or delirium, and this further contributes to cerebral ischemia if blood pressure drops below critical thresholds. Sedative agents alter cerebro-vascular reactivity and may significantly reduce CBF. Although disorders of brain perfusion and alteration of CBF and cerebral autoregulation are frequently observed in humans with sepsis, their exact role in the pathogenesis of SAE remains unknown. Brain perfusion can further become inadequate due to cerebral microcirculatory dysfunction, as evidenced in the experimental setting. Microvascular alterations can be implicated in the development of electrophysiological abnormalities observed during sepsis and contribute to neurological alterations in septic animals. The aim of this review is to provide an update on the pathophysiology of brain perfusion in sepsis, with a particular focus on human clinical investigation and novel tools for CBF monitoring in septic patients.