bluuebunny/crossref_metadata_2025 huggingface dataset:
Flood lavas on Earth, Io and Mars
Authors: Keszthelyi Laszlo , Self Stephen , Thordarson Thorvaldur
Published: February 2006

Flood lavas are major geological features on all the major rocky planetary bodies. They provide important insight into the dynamics and chemistry of the interior of these bodies. On the Earth, they appear to be associated with major and mass extinction events. It is therefore not surprising that there has been significant research on flood lavas in recent years. Initial models suggested eruption durations of days and volumetric fluxes of order 10
7
m
3
s
−1
with flows moving as turbulent floods. However, our understanding of how lava flows can be emplaced under an insulating crust was revolutionized by the observations of actively inflating pahoehoe flows in Hawaii. These new ideas led to the hypothesis that flood lavas were emplaced over many years with eruption rates of the order of 10
4
m
3
s
−1
. The field evidence indicates that flood lava flows in the Columbia River Basalts, Deccan Traps, Etendeka lavas, and the Kerguelen Plateau were emplaced as inflated pahoehoe sheet flows. This was reinforced by the observation of active lava flows of ≥100 km length on Io being formed as tube-fed flows fed by moderate eruption rates (10
2
–10
3
m
3
s
−1
). More recently it has been found that some flood lavas are also emplaced in a more rapid manner. New high-resolution images from Mars revealed ‘platy–ridged’ flood lava flows, named after the large rafted plates and ridges formed by compression of the flow top. A search for appropriate terrestrial analogues found an excellent example in Iceland: the 1783–1784 Laki Flow Field. The brecciated Laki flow top consists of pieces of pahoehoe, not aa clinker, leading us to call this ‘rubbly pahoehoe’. Similar flows have been found in the Columbia River Basalts and the Kerguelen Plateau. We hypothesize that these flows form with a thick, insulating, but mobile crust, which is disrupted when surges in the erupted flux are too large to maintain the normal pahoehoe mode of emplacement. Flood lavas emplaced in this manner could have (intermittently) reached effusion rates of the order of 10
6
m
3
s
−1
.
Carbonate isotope chemostratigraphy suggests revisions to the geological history of the West Finnmark Caledonides, northern Norway
Authors: Slagstad T. , Melezhik V.A. , Kirkland C.L. , Zwaan K.B. , Roberts D. , Gorokhov I.M. , Fallick A.E.
Published: February 2006

Strontium and carbon isotopic data from amphibolite-facies marbles of the Falkenes formation, Sørøy succession (structurally upper Kalak Nappe Complex) in West Finnmark, northern Norway, indicate that the marbles were deposited between 760 and 710 Ma. Marbles of similar age have previously been identified only in the Uppermost Allochthon in north–central Norway, where they are considered to have a Laurentian ancestry. A similar origin and tectonostratigraphic position appears likely for the Falkenes formation. In contrast, structurally lower units within the Kalak Nappe Complex appear to have Baltican affinities. This dichotomy requires that commonly held ideas regarding the tectonostratigraphy of the West Finnmark Caledonides be revised. Combined with recent U–Pb dating of zircon and monazite from rocks associated with the marbles, the isotopic data suggest that the Sørøy succession of the Kalak Nappe Complex is not a continuous, depositional sequence as previously thought, but rather consists of a number of disparate and probably unrelated thrust-sheets, assembled during Late Silurian, Scandian orogenesis. This work shows that the West Finnmark Caledonides share a generally similar tectonometamorphic history with certain other parts of the Scandinavian Caledonides, and contributes to already existing data that may allow ‘chemostratigraphic’ correlation and reconstruction of the entire Caledonian belt.
Upper Cretaceous carbon- and oxygen-isotope stratigraphy of hemipelagic carbonate facies from southern Tibet, China
Authors: Li Xianghui , Jenkyns Hugh C. , Wang Chengshan , Hu Xiumian , Chen Xi , Wei Yushuai , Huang Yongjian , Cui Jie
Published: February 2006

A high-resolution carbon-isotope curve derived from Upper Cretaceous hemipelagic sediments cropping out at Tingri, southern Tibet, shows similarities to patterns established on other continents, notably in the presence of a well-defined positive excursion across the Cenomanian–Turonian boundary where δ
13
C values exceed 3.5‰. From the upper Turonian to the lower Campanian, δ
13
C values generally decline, apart from a minor positive excursion in the middle Coniacian: a trend that departs from that recorded from Europe. Relatively low δ
13
C values (
c
. 1‰) at the Santonian–Campanian and Campanian–Maastrichtian boundaries in Tibet define a prominent broad positive excursion centred in the middle Campanian and terminated by an abrupt fall towards the close of the stage. When compared with data from Europe and North Africa, the δ
13
C values of the Tibetan section are generally lower by
c
. 1.5‰, except for the middle Campanian positive excursion where values (δ
13
C
c
. 2‰) are comparable with those documented from Europe and North Africa. These differences are interpreted as reflecting variable mixing of water masses carrying different carbon-isotope signatures, such that areas close to the major sinks of marine organic carbon recorded higher δ
13
C values than those located in more distal regions. Oxygen-isotope ratios, albeit affected by diagenesis, may record a palaeotemperature signal.
Convergent morphology in small spiral worm tubes (‘
Spirorbis
’) and its palaeoenvironmental implications
Authors: Taylor Paul D. , Vinn Olev
Published: February 2006

Calcareous tube-worms generally identified as

Spirorbis

range from Ordovician to Recent, often profusely encrusting shells and other substrates. Whereas Recent

Spirorbis

is a polychaete annelid, details of tube structure in pre-Cretaceous ‘

Spirorbis

’ suggest affinities with the Microconchida, an extinct order of possible lophophorates. Although characteristically Palaeozoic, microconchid tube-worms survived the Permian mass extinction before being replaced in late Mesozoic ecosystems by true

Spirorbis

. Recent

Spirorbis

is stenohaline but spirorbiform microconchids also colonized freshwater, brackish and hypersaline environments during the Devonian–Triassic. Anomalies in the palaeoenvironmental distributions of fossil ‘

Spirorbis

’ are explained with the recognition of this striking convergence between microconchids and true

Spirorbis

.
A review of coal mining induced fault reactivation in Great Britain
Authors: Donnelly L.J.
Published: February 2006

Fault reactivation has been observed at several locations in almost every British coalfield. The movement of faults during mining subsidence has been known for at least 150 years, but the affects and consequences are not widely appreciated by other geologists, engineers, insurers, builders, lawyers and planners. This has lead to widespread damage to land, houses, roads, railways, engineered structures (bridges, tunnels, dams), utilities (sewers, pipelines, cables). Disputed cases of fault reactivation have resulted in lands tribunals and claims for compensation for damage to land and property, often incurring significant financial losses. These sources of data on fault reactivation includes anecdotal accounts, archive information and detailed case examples supported with surveying observations. The reactivation of a fault in an area undergoing mining subsidence may result in the generation of a fault scarp along the ground surface, accompanied by compression or fissuring. Ground deformation caused by reactivated faults varies from subtle flexures across the ground surface to steeply inclined scarps, 3–4 m high and at least 4 km long. In the latter, this may influence the morphology of an entire moorland plateaux and has a contributory role in groundwater flow and the drainage of the landscape, or the initiation (and reactivation) of landslides. Not all types of faults reactivate when subject to mining subsidence stresses. Furthermore, movement along faults does not continue indefinitely. It is usually the principal faults which cross the coalfields and define structural blocks and cells that are more prone to reactivation. Several phases of fault reactivation are possible, during multi-seam (3+) mining operations, separated by periods of relative stability. In some circumstances, such as minewater rebound or residual mining subsidence, further movements along a previously reactivated fault are possible. The objectives of this paper are to provide, for the first time, a comprehensive account of reported and recorded cases of mining-induced fault reactivation in Britain. These have been compiled over a 15 years period, from 1990 to 2005. There are 227 recorded cases of fault reactivation and this is thought to represents a large under estimation of the actual number. This may be attributed to a relatively poor understanding of geology and fault reactivation mechanisms by past investigators. There was a tendency to ignore fault reactivation cases to reduce mining subsidence compensation claims. Furthermore, relatively fewer investigations were undertaken compared to the more conventional widespread mining subsidence observations. Many cases of fault reactivation have been undocumented, not recorded or incorrectly interpreted. This paper also aims to draw attention to potential geotechnical hazards, liabilities, risks and consequences associated with faulted ground.
Landslides in the Alaknanda Valley of Garhwal Himalaya, India
Authors: Sarkar S. , Kanungo D.P. , Patra A.K.
Published: February 2006

The occurrence of landslides is a recurring problem along the hill roads of Himalaya. Roads are often blocked due to landslides, which sometimes also leads to casualties. Identification of such unstable slopes is an imperative task to save life and property. The paper outlines features of major landslides along a National Highway in the Alaknanda valley of Garhwal Himalaya through photo documentation.
Antioxidants N-acetyl-l-cysteine and manganese(III)tetrakis (4-benzoic acid)porphyrin do not prevent β-cell dysfunction in rat islets cultured in high glucose for 1 wk
Authors: Khaldi M. Z. , Elouil H. , Guiot Y. , Henquin J. C. , Jonas J. C.
Published: February 2006

We previously showed that the stimulation of heme oxygenase-1 expression by high glucose and hydrogen peroxide (H2O2) in cultured rat islets is prevented by antioxidants and suggested that this effect of high glucose results from an oxidative stress. However, the role of oxidative stress in high-glucose-induced β-cell dysfunction is unclear. We therefore compared the preventative effects of N-acetyl-l-cysteine (NAC), a free radical scavenger, and manganese(III)tetrakis (4-benzoic acid)porphyrin (MnTBAP), a superoxide dismutase/catalase mimetic agent, on the alteration of stimulus-secretion coupling induced in rat islets by overnight exposure to hydrogen peroxide (H2O2-treated islets) or 1-wk culture in 30 vs. 10 mmol/l glucose (High-glucose vs. Control islets). The features of β-cell dysfunction differed between the two groups: reduced glucose-induced insulin secretion without changes in glucose sensitivity in H2O2-treated islets; increased sensitivity to glucose with parallel reductions in insulin content and maximal rate of glucose-induced insulin secretion in High-glucose islets. The latter alterations were accompanied by a decrease in preproinsulin without changes in pancreatic and duodenal homeobox gene 1 mRNA levels. The functional alterations induced by H2O2 were significantly prevented by addition of NAC or MnTBAP in the culture medium. In contrast, neither NAC nor MnTBAP affected the functional alterations induced by high glucose. These results suggest that β-cell dysfunction induced by 1-wk culture in high glucose does not result from an increase in oxidative stress.
Iron Imports. V. Transport of iron through the intestinal epithelium
Authors: Ma Yuxiang , Yeh Mary , Yeh Kwo-yih , Glass Jonathan
Published: February 2006

Iron absorption across the brush-border membrane requires divalent metal transporter 1 (DMT1), whereas ferroportin (FPN) and hephaestin are required for exit across the basolateral membrane. However, how iron passes across the enterocyte is poorly understood. Both chaperones and transcytosis have been postulated to account for intracellular iron transport. With iron feeding, DMT1 undergoes endocytosis and FPN translocates from the apical cytosol to the basolateral membrane. The fluorescent metallosensor calcein offered to the basolateral surface of enterocytes is found in endosomes in the apical compartment, and its fluorescence is quenched when iron is offered to the apical surface. These experiments are consistent with vesicular iron transport as a possible pathway for intracellular iron transport.
Longitudinal movements and resulting shear strain of the arterial wall
Authors: Cinthio Magnus , Ahlgren Åsa Rydén , Bergkvist Jonas , Jansson Tomas , Persson Hans W. , Lindström Kjell
Published: February 2006

There has been little interest in the longitudinal movement of the arterial wall. It has been assumed that this movement is negligible compared with the diameter change. Using a new high-resolution noninvasive ultrasonic method, we measured longitudinal movements and diameter change of the common carotid artery of 10 healthy humans. During the cardiac cycle, a distinct bidirectional longitudinal movement of the intima-media complex could be observed in all the subjects. An antegrade longitudinal movement, i.e., in the direction of blood flow, in early systole [0.39 mm (SD 0.26)] was followed by a retrograde longitudinal movement, i.e., in the direction opposite blood flow [−0.52 mm (SD 0.27)], later in systole and a second antegrade longitudinal movement [0.41 mm (SD 0.33)] in diastole. The corresponding diameter change was 0.65 mm (SD 0.19). The adventitial region showed the same basic pattern of longitudinal movement; however, the magnitude of the movements was smaller than that of the intima-media complex, thereby introducing shear strain and, thus, shear stress within the wall [maximum shear strain between the intima-media complex and the adventitial region was 0.36 rad (SD 0.26). These phenomena have not previously been described. Measurements were also performed on the abdominal aorta ( n = 3) and brachial ( n = 3) and popliteal ( n = 3) arteries. Our new information seems to be of fundamental importance for further study and evaluation of vascular biology and hemodynamics and, thus, for study of atherosclerosis and vascular diseases.
Cadmium and calcium uptake in isolated mitochondria-rich cell populations from the gills of the freshwater rainbow trout
Authors: Galvez Fernando , Wong Denise , Wood Chris M.
Published: February 2006

A novel cell isolation technique was used to characterize cadmium and calcium uptake in distinct populations of gill cells from the adult rainbow trout ( Oncorhynchus mykiss). A specific population of mitochondria-rich (MR) cell, termed the PNA+MR cell (PNA is peanut lectin agglutinin), was found to accumulate over threefold more109Cd than did PNA−MR cells, pavement cells (PV cells), and mucous cells during a 1-h in vivo exposure at 2.4 μg/l109Cd. In vitro109Cd exposures, performed in standard PBS and Cl−-free PBS, at concentrations from 1 to 16 μg/l109Cd, were also carried out to further characterize Cd2+uptake kinetics. As observed during in vivo experiments, PNA+MR cells accumulated significantly more109Cd than did other cell types when exposures were performed by an in vitro procedure in PBS. Under such conditions, Cd2+accumulation kinetics in all cell types could be described with Michaelis-Menten relationships, with Kmvalues of ∼3.0 μg/l Cd (27 nM) for both MR cell subtypes and 8.6 μg/l Cd (77 nM) for PV cells. In similar experiments performed in Cl−-free conditions, a significant reduction in109Cd accumulation in PNA+MR cells was seen but not in PNA−MR or in PV cells. In vitro45Ca fluxes were also performed to determine the cellular localization of Ca2+transport in these functionally distinct populations of gill cells.45Ca uptake was most pronounced in PNA+MR cells, with levels over threefold higher than those found in either PNA−MR or in PV cells. Results from the present study suggest that the PNA+MR cell type is a high-affinity and high-capacity site for apical entry of Cd2+and Ca2+in the gill epithelium of rainbow trout.
Vascular Na+/Ca2+exchanger: implications for the pathogenesis and therapy of salt-dependent hypertension
Authors: Iwamoto Takahiro
Published: February 2006

The Na+/Ca2+exchanger is an ion transporter that exchanges Na+and Ca2+in either Ca2+efflux or Ca2+influx mode, depending on membrane potential and transmembrane ion gradients. In arterial smooth muscle cells, the Na+/Ca2+exchanger is thought to participate in the maintenance of vascular tone by regulating cytosolic Ca2+concentration. Recent pharmacological and genetic engineering studies have revealed that the Ca2+influx mode of vascular Na+/Ca2+exchanger type-1 (NCX1) is involved in the pathogenesis of salt-dependent hypertension. SEA0400, a specific Na+/Ca2+exchange inhibitor that preferentially blocks the Ca2+influx mode, lowers arterial blood pressure in salt-dependent hypertensive models, but not in normotensive rats or other types of hypertensive rats. Furthermore, heterozygous mice with reduced expression of NCX1 are resistant to development of salt-dependent hypertension, whereas transgenic mice with vascular smooth muscle-specific overexpression of NCX1 readily develop hypertension after high-salt loading. SEA0400 reverses the cytosolic Ca2+elevation and vasoconstriction induced by nanomolar ouabain, as well as humoral factors in salt-loaded animals. One possibility is that circulating endogenous cardiotonic steroids may be necessary for NCX1-mediated hypertension. These findings help to explain how arterial smooth muscle cells in blood vessels contribute to salt-elicited blood pressure elevation and suggest that NCX1 inhibitors might be therapeutically useful for salt-dependent hypertension.
Salt intake and depletion increase circulating levels of endogenous ouabain in normal men
Authors: Manunta Paolo , Hamilton Bruce P. , Hamlyn John M.
Published: February 2006

High-salt diets elevate circulating Na+ pump inhibitors, vascular resistance, and blood pressure. Ouabain induces a form of hypertension mediated via the α2-Na+ pump isoform and the calcium influx mode of the vascular sodium calcium exchanger (NCX). Whereas elevated levels of an endogenous ouabain (EO) and NCX have been implicated in salt-sensitive hypertension, acute changes in sodium balance do not affect plasma EO. This study investigated the impact of longer-term alterations in sodium balance on the circulating levels and renal clearance of EO in normal humans. Thirteen normal men consumed a normal diet, high-salt diet, and hydrochlorothiazide (HCTZ), each for 5-day periods to alter sodium balance. EO and other humoral and urinary variables were determined daily. On a normal diet, urinary sodium excretion (140 ± 16 meq/day), plasma EO (0.43 ± 0.08 nmol/l) and urinary EO excretion (1.04 ± 0.13 nmol/day) were at steady state. On the 3rd day of a high-salt diet, urine sodium excretion (315 ± 28 meq/day), plasma EO (5.8 ± 2.2 nmol/l), and the urinary EO excretion (1.69 ± 0.27 nmol/day) were significantly increased, while plasma renin activity and aldosterone levels were suppressed. The salt-evoked increase in plasma EO was greater in older individuals, in subjects whose baseline circulating EO was higher, and in those with low renal clearance. During HCTZ, body weight decreased and plasma renin activity, aldosterone, and EO (1.71 ± 0.77 nmol/l) rose, while urinary EO excretion remained within the normal range (1.44 ± 0.31 nmol/day). Blood pressure fell in one subject during HCTZ. HPLC of the plasma extracts showed one primary peak of EO immunoreactivity with a retention time equivalent to ouabain. High-salt diets and HCTZ raise plasma EO by stimulating EO secretion, and a J-shaped curve relates sodium balance and EO in healthy men. Under normal dietary conditions, ∼98% of the filtered load of EO is reabsorbed by the kidney, and differences in the circulating levels of EO are strongly influenced by secretion and urinary excretion of EO. The dramatic impact of high-salt diets on plasma EO is consistent with its proposed role as a humoral vasoconstrictor that links salt intake with vascular function in hypertension.
Roles of glutamatergic and serotonergic mechanisms in reflex control of the external urethral sphincter in urethane-anesthetized female rats
Authors: Chang Hui-Yi , Cheng Chen-Li , Chen Jia-Jin J. , de Groat William C.
Published: February 2006

This study was conducted to examine reflex mechanisms that mediate urinary bladder and external urethral sphincter (EUS) coordination in urethane-anesthetized female Sprague-Dawley rats. We investigated the properties of EUS reflexes elicited by electrical stimulation of pelvic nerve afferent axons (pelvic-EUS reflex). The changes in the reflexes induced by bladder distension and administration of agonists or antagonists for glutamatergic or serotonergic receptors were examined. The reflexes consisted of an early response (ER, 18- to 22-ms latency) and a late, long-duration (>100-ms latency) response (LR), which consisted of bursts of activity at 20- to 160-ms interburst intervals. In a few experiments, a reflex with an intermediate (40- to 70-ms) latency was also identified. With the bladder empty, the ER, but not the LR, was detected in the majority of experiments. The LR was markedly enhanced when the bladder was distended. The ER remained, but the LR was abolished, after spinal cord transection at T8–T9. The ER and LR were significantly decreased 75 and 35%, respectively, by the N-methyl-d-aspartate receptor antagonist MK-801 (0.3 mg/kg iv), but only decreased 18 and 14%, respectively, by the α-amino-5-methylisoxazole-4-propionate receptor antagonist LY-215490 (3 mg/kg iv). The serotonin (5-HT1A) receptor agonist 8-hydroxy-2-(di- n-propylamino)-tetralin (1 mg/kg iv) enhanced spontaneous EUS activity and the pelvic-EUS reflex. WAY-100635 (0.1–1 mg/kg iv), a 5-HT1Aantagonist, reversed the effect of 8-hydroxy-2-(di- n-propylamino)-tetralin and suppressed EUS activity and the pelvic-EUS reflex. These results indicate that glutamatergic and serotonergic mechanisms are important in the reflex pathways underlying bladder- sphincter coordination in rats.
Testosterone and estrogen have opposing actions on inflammation-induced plasma extravasation in the rat temporomandibular joint
Authors: Flake Natasha M. , Hermanstyne Tracey O. , Gold Michael S.
Published: February 2006

The present study was designed to test the hypothesis that estrogen exacerbates inflammation of the temporomandibular joint (TMJ). Evans blue dye was used to quantify plasma extravasation (PE) around the rat TMJ. In an initial set of experiments, TMJ PE was compared in naïve intact male and female rats, as well as in both groups after complete Freund’s adjuvant (CFA)-induced inflammation of the TMJ. In contrast to our hypothesis, TMJ PE was significantly greater in both naïve and CFA-inflamed male rats than in females. To determine whether these differences were due to gonadal hormones, four additional groups of rats were studied: gonadectomized (Gx) males and females, Gx males with chronic testosterone (T) replacement, and Gx females with chronic estrogen (E) replacement. The sex difference in baseline TMJ PE appeared to reflect the actions of T. However, in the presence of TMJ inflammation, T augmented TMJ PE in males, while E attenuated TMJ PE in females. Changes in PE were also assessed in the contralateral TMJ. Results from this analysis indicated that there is a transient contralateral increase in TMJ PE in females but not males. Given that there is an inverse relationship between PE and joint damage, our results suggest that testosterone may mitigate, but estrogen may exacerbate, TMJ damage, particularly in the presence of overt inflammation. Importantly, our results may help explain both the higher prevalence and severity of temporomandibular disorder pain in females than males.
Physiological role of the α1- and α2-isoforms of the Na+-K+-ATPase and biological significance of their cardiac glycoside binding site
Authors: Dostanic-Larson Iva , Lorenz John N. , Van Huysse James W. , Neumann Jon C. , Moseley Amy E. , Lingrel Jerry B
Published: February 2006

An interesting feature of Na+-K+-ATPase is that it contains four isoforms of the catalytic α-subunit, each with a tissue-specific distribution. Our laboratory has used gene targeting to define the functional role of the α1- and α2-isoforms. While knockout mice demonstrated the importance of the α1- and α2-isoforms for survival, the knockin mice, in which each isoform can be individually inhibited by ouabain and its function determined, demonstrated that both isoforms are regulators of cardiac muscle contractility. Another intriguing aspect of the Na+-K+-ATPase is that it contains a binding site for cardiac glycosides, such as digoxin. Conservation of this site suggests that it may have an in vivo role and that a natural ligand must exist to interact with this site. In fact, cardiac glycoside-like compounds have been observed in mammals. Our recent study demonstrates that the cardiac glycoside binding site of the Na+-K+-ATPase plays a role in the regulation of blood pressure and that it mediates both ouabain-induced and ACTH-induced hypertension in mice. Whereas chronic administration of ouabain or ACTH caused hypertension in wild-type mice, it had no effect on blood pressure in mice with a ouabain-resistant α2-isoform of Na+-K+-ATPase. Interestingly, animals with the ouabain-sensitive α1-isoform and a ouabain-resistant α2-isoform develop ACTH-induced hypertension to a greater extent than wild-type animals. Taken together, these results demonstrate that the cardiac glycoside binding of the Na+-K+-ATPase has a physiological role and suggests a function for a naturally occurring ligand that is stimulated by administration of ACTH.
Tubular kidney injury molecule-1 in protein-overload nephropathy
Authors: van Timmeren Mirjan M. , Bakker Stephan J. L. , Vaidya Vishal S. , Bailly Veronique , Schuurs Theo A. , Damman Jeffrey , Stegeman Coen A. , Bonventre Joseph V. , van Goor Harry
Published: February 2006

Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 ± 313 vs. 18 ± 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/β-actin, 4.08 ± 2.56 vs. 0.52 ± 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 ± 1.19 vs. 0.39 ± 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 ± 592 vs. 87 ± 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression ( r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (α-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage.
Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation
Authors: Leffler Charles W. , Parfenova Helena , Jaggar Jonathan H. , Wang Rui
Published: February 2006

This review focuses on two gaseous cellular messenger molecules, CO and H2S, that are involved in cerebrovascular flow regulation. CO is a dilatory mediator in active hyperemia, autoregulation, hypoxic dilation, and counteracting vasoconstriction. It is produced from heme by a constitutively expressed enzyme [heme oxygenase (HO)-2] expressed highly in the brain and by an inducible enzyme (HO-1). CO production is regulated by controlling substrate availability, HO-2 catalytic activity, and HO-1 expression. CO dilates arterioles by binding to heme that is bound to large-conductance Ca2+-activated K+channels. This binding elevates channel Ca2+sensitivity, that increases coupling of Ca2+sparks to large-conductance Ca2+-activated K+channel openings and, thereby, hyperpolarizes the vascular smooth muscle. In addition to dilating blood vessels, CO can either inhibit or accentuate vascular cell proliferation and apoptosis, depending on conditions. H2S may also function as a cerebrovascular dilator. It is produced in vascular smooth muscle cells by hydrolysis of l-cysteine catalyzed by cystathione γ-lyase (CSE). H2S dilates arterioles at physiologically relevant concentrations via activation of ATP-sensitive K+channels. In addition to dilating blood vessels, H2S promotes apoptosis of vascular smooth muscle cells and inhibits proliferation-associated vascular remodeling. Thus both CO and H2S modulate the function and the structure of circulatory system. Both the HO-CO and CSE-H2S systems have potential to interact with NO and prostanoids in the cerebral circulation. Much of the physiology and biochemistry of HO-CO and CSE-H2S in the cerebral circulation remains open for exploration.
The structural basis of airways hyperresponsiveness in asthma
Authors: Brown Robert H. , Pearse David B. , Pyrgos George , Liu Mark C. , Togias Alkis , Permutt Solbert
Published: February 2006

We hypothesized that structural airway remodeling contributes to airways hyperresponsiveness (AHR) in asthma. Small, medium, and large airways were analyzed by computed tomography in 21 asthmatic volunteers under baseline conditions (FEV1= 64% predicted) and after maximum response to albuterol (FEV1= 76% predicted). The difference in pulmonary function between baseline and albuterol was an estimate of AHR to the baseline smooth muscle tone (BSMT). BSMT caused an increase in residual volume (RV) that was threefold greater than the decrease in forced vital capacity (FVC) because of a simultaneous increase in total lung capacity (TLC). The decrease in FVC with BSMT was the major determinant of the baseline FEV1( P < 0.0001). The increase in RV correlated inversely with the relaxed luminal diameter of the medium airways ( P = 0.009) and directly with the wall thickness of the large airways ( P = 0.001). The effect of BSMT on functional residual capacity (FRC) controlled the change in TLC relative to the change in RV. When the FRC increased with RV, TLC increased and FVC was preserved. When the relaxed large airways were critically narrowed, FRC and TLC did not increase and FVC fell. With critical large airways narrowing, the FRC was already elevated from dynamic hyperinflation before BSMT and did not increase further with BSMT. FEV1/FVC in the absence of BSMT correlated directly with large airway luminal diameter and inversely with the fall in FVC with BSMT. These findings suggest that dynamic hyperinflation caused by narrowing of large airways is a major determinant of AHR in asthma.
Differentially Variable Component Analysis: Identifying Multiple Evoked Components Using Trial-to-Trial Variability
Authors: Knuth Kevin H. , Shah Ankoor S. , Truccolo Wilson A. , Ding Mingzhou , Bressler Steven L. , Schroeder Charles E.
Published: February 2006

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons, either spontaneously or in response to external stimuli, provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult because detectors record signals simultaneously generated by various regions throughout the brain. We introduce a novel approach to this problem, the differentially variable component analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we demonstrate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. We then compare the source-separation capabilities of dVCA with those of principal component analysis and independent component analysis. Finally, we apply dVCA to neural ensemble activity recorded from an awake, behaving macaque—demonstrating that dVCA is an important tool for identifying and characterizing multiple components in the single trial.
Role of endothelial cell apoptosis in regulation of skeletal muscle angiogenesis during high and low salt intake
Authors: de Resende Micheline M. , Amaral Sandra L. , Munzenmaier Diane H. , Greene Andrew S.
Published: February 2006

Angiogenesis, under normal conditions, is a tightly regulated balance between pro- and antiangiogenic factors. The goal of this study was to investigate the mechanisms involved in the control of the skeletal muscle angiogenic response induced by electrical stimulation during the suppression of plasma renin activity (PRA) with a high-salt diet. Rats fed 0.4% or 4% salt diets were exposed to electrical stimulation for 7 days. The tibialis anterior (TA) muscles from stimulated and unstimulated hindlimbs were removed and prepared for gene expression analysis, CD31-terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) double-staining assay, and Bcl-2 and Bax protein expression by Western blot. Rats fed a low-salt diet showed a dramatic angiogenesis response in the stimulated limb compared with the unstimulated limb. This angiogenesis response was significantly attenuated when rats were placed on a high-salt diet. Microarray analysis showed that in the stimulated limb of rats fed a low-salt diet many genes related to angiogenesis were upregulated. In contrast, in rats fed a high-salt diet most of the genes upregulated in the stimulated limb function in apoptosis and cell cycle arrest. Endothelial cell apoptosis, as analyzed by CD31-TUNEL staining, increased by fourfold in the stimulated limb compared with the unstimulated limb. There was also a 48% decrease in the Bcl-2-to-Bax ratio in stimulated compared with unstimulated limbs of rats fed a high-salt diet, confirming severe apoptosis. This study suggests that the increase in endothelial cell apoptosis in TA muscle might contribute to the attenuation of angiogenesis response observed in rats fed a high-salt diet.
Pharmacological Treatment of the Irritable Bowel Syndrome and Other Functional Bowel Disorders
Authors: Mearin Fermín
Published: February 2006

Functional digestive disorders constitute one of the main causes of consultation in gastroenterology and primary health care. Is still unclear whether therapy has to be aimed to the gut, to the neural pathways controlling bowel motility and perception, or to the processing mechanisms of symptoms and disease behaviour. It is conceivable that in the next future better understanding of functional bowel disorders pathophysiology will help us to tailor treatment for different patients. At the moment, subclassification of the diverse patterns of symptomatology allows to adjust new treatments for irritable bowel syndrome (IBS) according to the clinical predominance for each patient. The knowledge of motor and sensorial response to different stimuli in IBS patients and the pathways to the central nervous system is an important source of information for the development of new molecules. Fiber-enriched diet is frequently given for constipation-predominant IBS. Loperamide, antispasmodic drugs and tricyclic antidepressants are nowadays the basis for pharmacological treatment of diarrhea- predominant IBS. The scientific evidence supporting this therapeutical approach is however limited. Visceral analgesics and serotonin agonists and antagonists may play an important therapeutical role in the near future. However, it is not likely that one single treatment will help every functional bowel disorder patient and many of them will need a more complex approach with a multidisciplinary therapy (diet, psychotherapy, medications).
Treatment of Functional Bowel Disorders: Is There Room for Antibiotics?
Authors: Corazza Gino Roberto , Di Stefano Michele , Scarpignato Carmelo
Published: February 2006

Small bowel bacterial overgrowth is a syndrome associated with a broad range of predisposing conditions, characterized by the presence of pathological amounts or types of bacteria at the level of the small bowel, clinically evident with a spectrum of symptoms such as diarrhea, flatulence, abdominal pain and bloating. Some of these symptoms are very common complaints in patients suffering from functional bowel disorders (FBDs). Although the pathophysiological mechanisms responsible for FBDs are certainly multifactorial and not yet completely understood, several pieces of evidence suggest that an increased metabolic activity of intestinal bacteria is responsible for gas-related intestinal symptoms in a large subgroup of patients. In addition, byproducts of colonic fermentation might be able to trigger symptoms in those patients displaying visceral hypersensitivity. Targeting enteric bacteria with antibiotics therefore represents a logical approach to FBDs. Although systemic antimicrobials have been mostly used in the past, the availability of poorly absorbed antibiotics like rifaximin, being safe and effective, has represented a step forward in the treatment of this challenging clinical condition.
Colonic Diverticular Disease: Pathophysiology and Clinical Picture
Authors: Parra-Blanco Adolfo
Published: February 2006

Colonic diverticulosis is the most frequent structural abnormality of the large bowel, although it was a rarity before the 20th century. Lifestyle changes in westernized societies with reduced fiber diet are supposed to be the main cause for its high prevalence nowadays. In African countries, where staple diet is rich in fiber, diverticulosis remains very infrequent. Prevalence increases with ageing too. A fiber-deficient diet and subsequent reduction in bowel content volume would lead to increased intraluminal pressures and colonic segmentation, thus promoting diverticula formation. Animal and human studies have shown increased intracolonic pressures in patients with diverticulosis. Alterations in colonic muscle properties, collagen metabolism and in the interactions of the extracellular matrix components may play a role in remodelling the gut wall in diverticular disease. At least one fourth of patients with diverticulosis will develop symptoms, sometimes overlapping with irritable bowel syndrome, but 10–25% will suffer diverticulitis and 3–5% diverticular bleeding. Conservative medical management is usually sufficient in the first episode of diverticulitis, but surgical treatment is generally advocated in recurrences. Diverticular bleeding is a major cause of lower digestive haemorrhage, but generally self-limited. With the application of therapeutic endoscopic and angiographic methods, emergency surgery can often be avoided.
Management of Colonic Diverticular Disease
Authors: Frieri Giuseppe , Pimpo Maria Teresa , Scarpignato Carmelo
Published: February 2006

Diverticular disease of the colon is a complex syndrome that includes several clinical conditions, each needing different therapeutic strategies. In patients with asymptomatic diverticulosis, only a fiber-rich diet can be recommended in an attempt to reduce intraluminal pressure and slow down the worsening of the disease. Fiber supplementation is also indicated in symptomatic diverticulosis in order to get symptom relief and prevent acute diverticulitis. In this regard, the best results have been obtained by combination of soluble fiber, like glucomannan, and poorly absorbed antibiotics, like rifaximin, given 7–10 days every month. For uncomplicated diverticulitis the standard therapy is liquid diet and oral antimicrobials, usually ciprofloxacin and metronidazole. Hospitalization, bowel rest, and intravenous antibacterial agents are mandatory for complicated diverticulitis. Haemorrhage is usually a self-limited event but may require endoscopic or surgical treatment. Once in remission, continuous fiber intake and intermittent course of rifaximin may improve symptoms and reduce diverticulitis recurrence. These preventive strategies will likely improve patients’ quality of life and reduce management costs. A surgical approach in diverticular disease is needed in 15–30% of cases and consists of removing the intestinal segment affected by diverticula. It is indicated in diffuse peritonitis, abscesses, fistulas, stenosis and after the second to fourth attack of uncomplicated diverticulitis. Young people and immunocompromised patients are more likely to be operated.
Inflammatory Bowel Disease: Current Therapeutic Options
Authors: Domènech Eugeni
Published: February 2006

Medical management of inflammatory bowel diseases (IBD) includes two treatment strategies: induction and maintenance of remission. 5-Aminosalycilates are mostly used for mild active IBD and for maintenance treatment in ulcerative colitis (UC). Glucocorticoids remain, despite their frequent (and occasionally severe) side effects, as the mainstay for induction of remission in moderate to severe active IBD, both UC and Crohn’s disease (CD). Cyclosporine and infliximab have emerged as the main, rapid-acting, alternatives in steroid-refractory UC and CD, respectively. Thiopurines (azathioprine and 6-mercaptopurine) are the most efficient and used immunomodulators in IBD; steroid refractoriness, steroid dependency, and long-term maintenance of remission for both UC and CD are their main indications. Methotrexate and infliximab may be used in the same clinical settings as thiopurines in CD, but not in UC; however, these drugs are a second-line treatment because of safety profile and economic costs.
Antimicrobials in the Management of Inflammatory Bowel Disease
Authors: Gionchetti Paolo , Rizzello Fernando , Lammers Karen M. , Morselli Claudia , Tambasco Rosy , Campieri Massimo
Published: February 2006

Many experimental and clinical observations suggest a potential role for intestinal microflora in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics may therefore represent a potentially effective therapeutic option. However, the available studies do not support the use of antimicrobials in ulcerative colitis and larger studies are required. These drugs are however effective in treating septic complications of Crohn’s disease (CD). The use of antibacterial agents as primary therapy for CD is more controversial, although this approach is frequently and successfully adopted in clinical practice. Despite the fact that properly controlled trials have been not carried out, antimicrobials are the mainstay of the treatment of pouchitis. Rifaximin is a poorly absorbed, broad-spectrum antibiotic that, thanks to its efficacy and long-term safety, could represent the preferred tool of manipulating enteric flora in patients with IBD. Preliminary data suggest that rifaximin may be beneficial in the treatment of active ulcerative colitis (and pouchitis), mild to moderate CD as well as prevention of post-operative recurrence of CD.
Hepatic Encephalopathy: From Pathophysiology to Treatment
Authors: Mas Antoni
Published: February 2006

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome due to hepatic dysfunction and porto-systemic shunting of the intestinal blood. Cirrhosis is the most frequent liver disease causing HE. On most occasions, HE appears due to a superimposed precipitating factor (gastrointestinal bleeding, infections, renal and electrolyte disturbances, etc.). Ammonia produced in colon by intestinal bacteria is the main toxic substance implicated in the pathogenesis of HE. Other mechanisms, such as changes in the GABA-benzodiazepine system, accumulation of manganese into the basal ganglia of the brain, changes in blood-brain barrier and neurotransmission disturbances are also present. Clinical manifestations of HE may vary widely, from minimal neurologic changes, only detected with specific tests, to deep coma. Treatment of HE should be directed to controlling the precipitating factors, as well as therapies aimed at correcting the above-mentioned pathophysiological changes, mainly reduction of blood ammonia levels. Artificial liver support systems may play a role in the future. Liver transplantation should be evaluated as a definitive therapy in all cases of HE.
Epidemiology, Etiology and Pathophysiology of Traveler’s Diarrhea
Authors: Gascón Joaquim
Published: February 2006

Traveler’s diarrhea (TD) is the most frequent health problem in travelers to developing countries. Several personal and environmental risk factors are at the basis of TD acquisition and are discussed in this paper. TD is caused by a wide range of infectious organisms, ETEC and EAEC bacteria strains being the main enteropathogens incriminated in TD. Other causative bacteria are: Shigella spp., Campylobacter spp., Vibrio spp., Aeromonas spp., Salmonella spp., and Plesiomonas spp. Parasite species are also included: Cyclospora cayetanensis, Giardia lamblia, Crystosporidium, Entamoeba histolytica, as well as viruses: rotavirus, adenovirus, Norwalk virus. Due to the great diversity of pathogens incriminated, several pathophysiological mechanisms have been described and some of them are still poorly understood. The clinical symptoms present are also quite variable, although inflammatory and non-inflammatory diarrhea have been established as a classical and basic classification of diarrhea.
Prevention and Treatment of Traveler’s Diarrhea
Authors: Castelli Francesco , Saleri Nuccia , Tomasoni Lina Rachele , Carosi Giampiero
Published: February 2006

Diarrhea, mostly due to bacterial infection of the gut, is the most frequent health complaint in the international traveler, affecting 20–70% of the traveling population depending on the destination and other factors. It is usually benign and self-limiting in nature, but symptoms may occasionally be distressing causing modifications of normal activities and sometimes confinement to bed or hospitalization. Prevention of traveler’s diarrhea should ideally be based on dietary restrictions, but experience shows that this target is extremely difficult to achieve. Antibiotic chemoprophylaxis should be restricted to selected groups of travelers at risk of severe complications of diarrhea or when diarrhea-driven alterations of planned activities are highly undesirable (crit- ical trips). The effectiveness of alternative prophylactic approaches, such as vaccination or the use of probiotics, still awaits confirmation. Treatment of mild diarrheal cases without intestinal symptoms may be limited to rehydration with or without antimotility agents. When antibiotic therapy is considered, non-absorbable antibiotics, such as rifaximin, may be considered a valid alternative to systemic antibiotics to treat uncomplicated cases, leaving fluoroquinolones and/or azithromycin for use in more severe cases or when invasive pathogens are suspected. Indeed, therapeutic use of doxycycline and trimethoprim-sulfamethoxazole (TMP-SMX) is limited by widespread resistance of many enteropathogens. The addition of loperamide or other antimotility agents usually provides symptom relief and further shortens the duration of illness and may be therefore safely adopted in the healthy adult unless dysentery is present.