bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF STEADY SHEAR STRESS ON FLUID FILTRATION THROUGH THE RABBIT ARTERIAL WALL IN THE PRESENCE OF MACROMOLECULES
Authors: Karmakar Nivedita , Dhar Promila
Published: June 2007

1. Transport properties of the arterial wall in general and endothelial cells in particular are known to be sensitive to fluid flow generated shear stress.

2. The effect of steady wall shear stress was studied in vitro on transmural water filtration in the presence of a control perfusate (10mg/mL bovine serum albumin) and a test perfusate (50 mg/mL Dextran 500). The latter is a macromolecule with certain physical properties comparable to those of the circulating low density lipoproteins. Dextran 500 is a neutral polysaccharide carrying no charge groups.

3. Male rabbits were anaesthetized with sodium pentobarbital and one of the common carotid arteries was cannulated and excised.

4. Fluid flux across the artery wall was measured at a constant transmural pressure (150 cm H2O) in the presence and absence of luminal flow of the perfusate.

5. Luminal flow produced an average increase by 21% in the filtration flux relative to its value under static conditions with 10 mg/mL bovine serum albumin in the perfusate. In the presence of 50 mg/mL Dextran 500 in the perfusate an average reduction by 36% was observed in fluid flux when luminal flow was imposed in the artery.

6. The increase in flux with the control perfusate may be due to a structural alteration of the glycocalyx fibre matrix caused by flow imposed shear stress. The observed decrease in flux with 50 mg/mL Dextran 500 may be accounted for by the deformation of the dextran polymer chains when subjected to shear stress. Although intact molecules are likely to be excluded by the glycocalyx, parts of the chain may insert themselves in the network and enhance the steric exclusion of water. Also, decreased hydration of the medial interstitium may increase medial resistance to fluid transport.
IBUDILAST REDUCES INTRACELLULAR CALCIUM ELEVATION INDUCED BY IN VITRO ISCHAEMIA IN GERBIL HIPPOCAMPAL SLICES
Authors: Yanase Hisato , Mitani Akira , Kataoka Kiyoshi
Published: June 2007

1. A microfluorometry was carried out to investigate the effect of 3‐isobutyryl‐2‐isopropylpyrazolo[1,5‐a]pyridine (ibudilast) on changes in levels of intracellular calcium concentration ([Ca2+]i) induced by in vitro ischaemia in the CA1 field of gerbil hippocampal slices.

2. When slices, loaded with a calcium ion sensitive dye (rhod‐2) were exposed to a glucose‐free physiological medium equilibrated with a 95% N2/5% CO2 gas mixture (standard in vitro ischaemia), a large [Ca2+]i elevation was detected approximately 5 min after the beginning of in vitro ischaemia.

3. When slices were perfused with the in vitro ischaemic medium containing 43 μmol/L ibudilast, a [Ca2+]i elevation was still observed; however, the extent of the increase in [Ca2+]i was significantly depressed in all subregions of the hippocampal slices.

4. The extent of this inhibitory effect of ibudilast on the in vitro ischaemia‐induced [Ca2+]i elevation was in a similar range as those of Ca2+ blockers, including (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cycloheptan‐5,10‐imine maleate (MK‐801), flunarizine and dantrolene.

5. Similar [Ca2+]i increases in the CA1 field were induced by a Ca2+‐free in vitro ischaemia, a high concentration of KCl or by specific agonists for glutamate receptor subtypes (N‐methyl‐d‐aspartate (NMDA), (s)‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) and kainate); these increases were also depressed with 43 μmol/L ibudilast present in the perfusion medium.

6. These results indicate that ibudilast may act by depressing the Ca2+ accumulation during and shortly after ischaemia, a possible pharmacological action of ibudilast that leads to the amelioration of ischaemic injury in the central nervous system.
DIFFERENCES IN THE DENSITY OF BAROSENSITIVE NEURONS IN THE MEDULLA OF SPONTANEOUSLY HYPERTENSIVE AND WISTAR‐KYOTO RATS
Authors: Xiong Yu , Takayama Kiyoshige , Miura Mitsuhiko
Published: June 2007

1. The density of barosensitive neurons in the medulla was examined in spontaneously hypertensive rats (SHR) and in normotensive Wistar‐Kyoto (WKY) rats. In control experiments, rats were sham‐operated, while in test experiments arterial baroreceptors were stimulated by pressor responses to i.v. administration of phenylephrine and the density of c‐Fos‐labelled neurons was immunocytologically examined.

2. In both control and test experiments, c‐Fos‐labelled neurons were distributed in cardiovascular control sites: the nucleus trac‐tus solitarii (NTS) and the caudal and rostral ventrolateral medullas (CVLM/RVLM).

3. In both WKY rats and in SHR, the total density of labelled neurons in test experiments was significantly higher than in control experiments.

4. In control experiments, no significant difference was found in the distribution and density of labelled neurons in the NTS and in the CVLM/RVLM between WKY rats and SHR.

5. In test experiments, no significant difference was found in the distribution and density of labelled neurons in the NTS between WKY rats and SHR.

6. In test experiments in SHR, the density of labelled neurons in the CVLM just caudal to the obex level was significantly higher than that in WKY rats, whereas the density of labelled neurons in WKY rats in the RVLM just rostral to the obex level was significantly higher than that in SHR.

7. These results indicate that stimulation of the arterial baro‐receptor induces strain‐specific differences in the density of barosensitive neurons in the CVLM/RVLM near the obex level.
CONTRACTILE PROPERTIES OF AFFERENT AND EFFERENT ARTERIOLES
Authors: Ito Sadayoshi , Abe Keishi
Published: June 2007

1. The balance of vascular tone of the afferent and efferent arteriole is a crucial determinant of glomerular haemodynamics. Despite their intimate anatomical relationship in the juxtaglomerular apparatus, the mechanisms that regulate afferent and efferent arteriolar tone are different.

2. In the afferent arteriole, two intrinsic mechanisms, the myogenic response and macula densa‐mediated tubuloglo‐merular feedback (TGF) play a dominant role, maintaining the glomerular filtration rate (GFR) at a constant level over a wide range of renal perfusion pressure. Studies have shown that these two mechanisms are modulated by nitric oxide (NO). In addition, an interaction between TGF and angiotensin II (AngII) seems to be essential to maintaining GFR despite large variations in daily intake of salt and water.

3. In the efferent arteriole, neither myogenic response nor TGF seems to be important, while AngII is one major factor involved in the control of vascular resistance. In addition, recent studies have provided evidence that NO and prostaglandins produced by the glomerulus may control resistance of the downstream efferent arteriole.

4. As the early segment of the efferent arteriole resides within the glomerulus, various autacoid hormones produced by the glomerulus may reach and directly act on this segment, thereby controlling the glomerular capillary pressure. Thus, it would be important to understand the differences in the mechanisms operating at the afferent and efferent arteriole, as well as their alterations in various physiological and pathological conditions.
LONG‐TERM SYMPATHO‐EXCITATORY EFFECT OF ANGIOTENSIN II: A MECHANISM OF SPONTANEOUS AND RENOVASCULAR HYPERTENSION
Authors: Fink Gregory D.
Published: June 2007

1. The peptide hormone angiotensin II (AngII) is acknowledged to be an important factor in the pathophysiology of hypertension. This is particularly the case in hypertension caused by luminal narrowing of one renal artery, (i.e. renovascular hypertension). The primary mechanism by which AngII raises blood pressure, however, is disputed. Strong arguments can be made supporting either vascular contraction, effects on renal excretion of sodium and water, or trophic actions on cardiovascular structures as the key element. In this paper I review evidence that AngII influences blood pressure by modulating autonomic nervous system activity. Modulation can occur at both the peripheral and central aspects of the autonomic system, but I focus on brain pathways involved in determining sympathetic nervous system activity.

2. Experimental and clinical investigations are cited to support the hypothesis that sympathetically mediated pressor effects are increased by both circulating and brain‐derived AngII in hypertension. Recent work points specifically to sympathetic pre‐motor neurons in the rostral ventrolateral medulla (RVLM) as a critical site of action of brain AngII in normoten‐sive and hypertensive animals.

3. This same set of neurons appears to be an important relay in the sympatho‐excitatory response to circulating AngII initiated at circumventricular organs, particularly the area pos‐trema. AngII has important effects on the baroreflex. These do not mediate the sympatho‐excitation elicited by circulating AngII, but rather mask its expression.

4. Substantial data support the hypothesis that increased blood concentrations of AngII in renovascular hypertension elevate blood pressure by causing neurogenic vasoconstriction mediated through the area postrema and RVLM.
TISSUE VARIATION OF ACUTE HAEMODYNAMIC CHANGES BY NG‐NITRO‐L‐ARGININE IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE AND WISTAR‐KYOTO RATS
Authors: Higashino H. , Simeonova K. , Lambev I. , Suzuki A.
Published: June 2007

1. The acute effects of nitric oxide synthase inhibition on the haemodynamics in stroke‐prone spontaneously hypertensive (SHRSP) and normotensive Wistar‐Kyoto (WKY) rats were investigated using radiolabeled microspheres.

2. Intravenous administration of 3 and 6 mg/kg NG‐nitro‐L ‐arginine (l.‐NNA) caused a significant increase in total peripheral resistance, a decrease in cardiac output and an increase in blood pressure in both SHRSP and WKY rats.

3. Significant decreases in regional blood flow (RBF) in the lung, muscle and stomach of WKY rats were observed following L‐NNA administration.

4. NG‐nitro‐L ‐arginine produced a 70% increase in brain regional blood flow at a dose of 6 mg/kg only in SHRSP.

5. There was a variation in the involvement of nitric oxide (NO) in different tissues.

6. It is concluded that hypertension in SHRSP augments NO‐mediated vasodilation.
EFFECTS OF VERATRIDINE ON THE ACTION POTENTIALS AND CONTRACTILITY OF RIGHT AND LEFT VENTRICLES FROM NORMO‐ AND HYPERTENSIVE RATS
Authors: Nand Vinita , Doggrell Sheila A. , Barnett Carolyn W.
Published: June 2007

1. We have studied the effects of prolonging the opening of sodium channels with veratridine on the action potentials (AP) and contractility of isolated right and left ventricles of Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). It was examined whether the effects of veratridine were altered in the SHR right ventricle in the absence of hypertrophy. The main aim of the present study was to test the hypothesis that the effects of veratridine were altered in the SHR left ventricle in the presence of hypertrophy.

2. The tail‐cuff pressures of 14‐ and 22‐week‐old, but not 5‐week‐old, SHR were greater than those of the WKY rat. At 14 weeks of age the SHR left, but not right, ventricle had developed hypertension‐associated hypertrophy.

3. The AP and contractions and the ability of veratridine to prolong the AP and act as a positive inotrope were similar in the right ventricles from 22‐week‐old WKY rats and SHR. The effects of veratridine and the AP and contractions of left ventricles of 5‐, 14‐ and 22‐week‐old WKY rats and of 5‐ and 14‐week‐old SHR were also similar.

4. The AP of the left ventricles of 22‐week‐old SHR were prolonged by 3 ms at the action potential duration (APD)50 and APD90 levels. The contractions to cardiac stimulation and the maximum combined force responses to cardiac stimulation and isoprenaline were reduced in the left ventricles of 22‐week‐old SHR compared with WKY rats and younger SHR.

5. The effectiveness of veratridine in prolonging the AP and augmenting the contractions to cardiac stimulation was reduced in the hypertrophied left ventricle of 22‐week‐old, but not 14‐week‐old, SHR.

6. In summary, the response to prolonging the opening of sodium channels with veratridine is not altered in the SHR right ventricle. However, in left ventricles of the hypertrophied 22‐week‐old, but not 14‐week‐old, SHR the effects of veratridine are reduced and this demonstrates that the response to prolonging the opening of sodium channels is changed in persistent hypertension‐associated hypertrophy.
PSYCHOMOTOR PERFORMANCE DURING INITIAL STAGE OF EXPOSURE TO HALOTHANE, ENFLURANE, ISOFLURANE AND SEVOFLURANE IN MICE
Authors: Komatsu Hisao , Nogaya Junko , Kuratani Norihumi , Ueki Masaaki , Yokono Satoshi , Ogli Kenji
Published: June 2007

1. The dose‐response relationship during the pre‐anaesthetic and pre‐equilibrium state of four inhalation anaesthetics (halothane, enflurane, isoflurane and sevoflurane) on fixed‐ratio schedule‐controlled behaviour was studied in mice.

2. Animals exposed to halothane, enflurane and isoflurane showed a biphasic pattern (i.e. a significant incremental increase in psychomotor responses at low inspired concentrations (0.1‐0.4%) and decrements at greater concentrations) in a dose‐dependent manner. Mean peak responses (per cent of control) were 132.3 (P<0.01 vs control), 124.0 (P<0.05) and 116.7% (P<0.05) at 0.1% halothane, 0.3% enflurane and 0.2% isoflurane, respectively.

3. Sevoflurane did not increase schedule‐controlled behavioural responses at any concentration.

4. The effect of subanaesthetic concentrations of inhalation anaesthetics on psychomotor performance can be evaluated as changes in the response rate in schedule‐controlled behaviour.
FUNCTION IN NEUROTOXICITY: INDEX OF EFFECT AND ALSO DETERMINANT OF VULNERABILITY
Authors: Ray DE
Published: June 2007

1. In neurotoxicity, functional indices may be the only available measures of effect, as many potent neurotoxic agents produce no morphological change. Examples of these are strychnine, dieldrin and pyrethroids, which produce excitation but no pathology, and barbiturates, xylene and lithium, which produce depression but no pathology.

2. In other cases where both functional and morphological effects are seen, functional measures often produce the most convenient, if not always the most specific, indices of toxicity. Appropriate functional measures can be highly sensitive, both in humans and in experimental animals, and can also give vital mechanistic information. However, it is essential that functional measures are reproducible and interpretable (some behavioural measures are not) and also provide a reasonably exacting test of function (passive observation of resting behaviour can miss many effects).

3. In addition to their use as an index of toxicity, changes in function, even within the normal range, can themselves influence susceptibility to toxins. Tissue perfusion can determine delivered dose and is influenced by function, while metabolic transformation is modified by nutritional state. Nutritional state can also influence absorption, with anaemia enhancing manganese toxicity and calcium deficiency enhancing lead toxicity. Functional activity can influence target susceptibility directly: thus, noise exposure enhances the ototoxicity of carbon monoxide, toluene or aminoglycoside antibiotics; noise, motor activity or anaesthesia all influence the central neurotoxicity of dinitrobenzene or metronidazole; motor activity enhances the peripheral nerve toxicity of lead or thallium; and nerve regeneration enhances the toxicity of hexane. These functional factors can be very important in determining individual susceptibility.
SYMPATHETIC MODULATION OF SENSORY NERVE ACTIVITY WITH AGE: HUMAN AND RODENT SKIN MODELS
Authors: Khalil Z , LeVasseur S , Merhi M , Helme RD
Published: June 2007

1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing.

2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses.

3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model.

4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model.

5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low‐frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency o. stimulation.
Experimental Biology 1997 Symposium on Neurobiology of Thennoregulation: Role of Stress: POISONS AND FEVER
Authors: Gordon Christopher J. , Rowsey Pamela J.
Published: June 2007

1. Dysfunction of the thermoregulatory system is one of many pathologies documented in experimental animals and humans exposed to toxic chemicals. The mechanism of action responsible for many types of poison‐induced fevers is not understood. Some elevations in body temperature are attributed to the peripheral actions of some poisons that stimulate metabolic rate and cause a forced hyperthermia. Exposure to organophosphate (OP) pesticides and certain metal fumes appears to cause a prolonged, regulated elevation in body temperature (Tb).

2. Activation of cyclo‐oxygenase (COX) and the production of prostaglandin (PG)E2 in central nervous system (CNS) thermoregulatory centres is required to elicit a fever. Activating the COX‐PGE2 pathway by a poison may occur by one of three mechanisms: (i) induction of cell‐mediated immune responses and the subsequent release of cytokines; (ii) induction of lipid peroxidation in the CNS; and (iii) direct neurochemical activation.

3. Radiotelemetric monitoring of core temperature in unstressed rodents has led to an experimental animal model of poison‐induced fever. Rats administered the OP agents chlorpyrifos and diisopropyl fluorophosphate display an initial hypothermic response lasting approximately 24 h, followed by an elevation in diurnal core temperature for 24–72 h after exposure. The hyperthermia is apparently a result of the activation of the COX‐PGE2 pathway because it is blocked by the anti‐pyretic sodium salicylate. Overall, the delayed hyperthermia resulting from OP exposure involves activation of thermoregulatory pathways that may be similar to infectionmediated fever.
ELECTROPHYSICAL PROPERTIES, SYNAPTIC TRANSMISSION AND NEUROMODULATION IN SEROTONERGIC CAUDAL RAPHE NEURONS
Authors: Li Yu‐Wen , Bayliss Douglas A.
Published: June 2007

1. We studied electrophysiological properties, synaptic transmission and modulation by 5‐hydroxytryptamine (5‐HT) of caudal raphe neurons using whole‐cell recording in a neonatal rat brain slice preparation; recorded neurons were identified as serotonergic by post‐hoc immunohistochemical detection of tryptophan hydroxylase, the 5‐HT‐synthesizing enzyme.

2. Serotonergic neurons fired spontaneously (approximately 1 Hz), with maximal steady state firing rates of < 4 Hz. 5‐Hydroxytryptamine caused hyperpolarization and cessation of spike activity in these neurons by activating inwardly rectifying K+ conductance via somatodendritic 5‐HT1A receptors.

3. Unitary glutamatergic excitatory post‐synaptic potentials (EPSP) and currents (EPSC) were evoked in serotonergic neurons by local electrical stimulation. Evoked EPSC were potently inhibited by 5‐HT, an effect mediated by presynaptic 5‐HTIB receptors.

4. In conclusion, serotonergic caudal raphe neurons are spontaneously active in vitro; they receive prominent glutamatergic synaptic inputs. 5‐Hydroxytryptamine regulates serotonergic neuronal activity of the caudal raphe by decreasing spontaneous activity via somatodendritic 5‐HTIA receptors and by inhibiting excitatory synaptic transmission onto these neurons via presynaptic 5‐HTIB receptors. These local modulatory mechanisms provide multiple levels of feedback autoregulation of serotonergic raphe neurons by 5‐HT.
CENTRAL REGULATION OF AUTONOMIC FUNCTION: NO BRAKES?
Authors: Krukoff Teresa L.
Published: June 2007

1. Nitric oxide (NO) is formed by neuronal NO synthase (nNOS) and acts as a non‐conventional neurotransmitter in the brain. A growing body of evidence supports the hypothesis that NO acts to decrease sympathetic output to the periphery; these effects may occur at several autonomic sites. The present review describes studies from our laboratory that address this hypothesis.

2. Restraint stress activates putative NO‐producing neurons in many autonomic centres: preoptic area, medial septum, amygdala, hypothalamus, including the paraventricular nucleus (PVN), raphe nuclei, nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM). These results suggest that NO is directly or indirectly involved in regulating sympathetic output to the periphery.

3. Systemic angiotensin II (Angll) activates putative NO‐producing neurons in the PVN. These neurons may be activated either by the increases in arterial pressure that accompany Angll injections or due to activation of AngII‐containing neural pathways.

4. Hypotension is associated with the activation of putative NO‐producing PVN neurons, small numbers of which also project to the NTS or VLM. As the majority of activated neurons is in the magnocellular division, NO production may be related to the production of vasopressin.

5. Adult spontaneously hypertensive rats (SHR) show increased gene expression of nNOS in the hypothalamus, dorsal medulla and caudal VLM. These differences are not present in young prehypertensive SHR, suggesting that the changes in gene expression in adult rats are associated with the increased sympathetic nerve activity found in these rats.

6. Gene expression of nNOS is altered in the hypothalamus and caudal VLM of renal hypertensive rats at 3 and 6 weeks after surgical induction of hypertension. Contrasting results at the two time points may be due to differing underlying physiological processes that characterize the two stages of renal hypertension.

7. Nitric oxide may affect sympathetic output through several possible mechanisms. These include affecting production of the second messenger cGMP and interactions with more classical neurotransmitters or with neurohormonal systems in the brain.
RELATIONSHIPS BETWEEN ISOMETRIC AND ISOTONIC MECHANICAL PARAMETERS AND CROSS‐BRIDGE KINETICS
Authors: Rossmanith Gunther H. , Tjokorda Oka B.
Published: June 2007

1. Isometric and isotonic measures have been widely used both to characterize muscular contraction in striated muscle and to compare the mechanical properties of striated muscle types for a wide variety of species. The interrelationship of these measures and their interpretation, in terms of underlying cross‐bridge mechanisms, requires clarification.

2. We demonstrate that a strain‐dependent three‐state model can simulate these isometric and isotonic mechanics and offer a unified explanation for these mechanics in terms of cross‐bridge kinetics.

3. Our exploration reveals the partial view each individual measure of mechanics provides and emphasizes the complementary insights the various isometric and isotonic measures give of the underlying cross‐bridge kinetics.
CYTOCHROME P‐450‐DEPENDENT ARACHIDONATE METABOLITES AND RENAL FUNCTIONS IN THE LYON HYPERTENSIVE RAT
Authors: Messer‐Létienne I. , Bernard N. , Benzoni D. , Sassard J.
Published: June 2007

1. The present work aimed to assess the role of cytochrome P‐450 (CP‐450) metabolites of arachidonic acid such as epoxy‐eicosatrienoic (EET) and hydroxyeicosatetraenoic acids (HETE) in the renal vasoconstriction and decreased natriuresis exhibited by genetically hypertensive (LH) rats of the Lyon strain.

2. The experiment was performed on single‐pass isolated perfused kidney preparations from 8‐week‐old male LH rats and their low blood pressure (LL) controls. The effects of miconazole (an inhibitor of the formation of EET) and of 17‐octadecynoic acid (17‐ODYA, an inhibitor of both EET and HETE synthesis) were studied before and after stimulation of the kidneys with two noradrenaline (NA) infusions (65 and 110 nmol/L).

3. Unstimulated LH kidneys (n= 12) differed from LL {n= 12) by increased vascular resistance (RVR) and decreased glomerular filtration rate and urinary sodium excretion (UNaV).

4. Miconazole (1 μmol/L) did not change the functions of LH and LL unstimulated kidneys, but blunted the vasoconstrictor response to NA (110 nmol/L), the difference being significant in LH kidneys only (1.7±0.2 vs 3.6±1.2 mmHg/mL per min per g; P<0.05).

5. Addition of 17‐ODYA (3 μmol/L) to miconazole did not modify RVR in LH and LL kidneys or the response to NA infusion. On the contrary, it increased UNaV, the differences being significant in LH kidneys only (22.9±1.4 vs 17.5±1.4 μmol/min per g; P<0.05 after NA 110 nmol/L).

6. It is suggested that EET may contribute to the elevated RVR and HETE to the reduced ability to excrete sodium, of LH kidneys.
RESTORATION OF NITRIC OXIDE FUNCTION IN HUMAN HYPERLIPIDAEMIA, CONGESTIVE HEART FAILURE AND LIVER CIRRHOSIS
Authors: Chin‐Dusting Jaye PF , Kaye David M.
Published: June 2007

1. There is accumulating evidence for a range of abnormalities in the nitric oxide (NO) signalling cascade in human cardiovascular disorders.

2. In the present review we assess the literature detailing such evidence in early (hyperlipidaemia) and end‐stage (heart failure) disease, with emphasis on the mechanisms by which the disturbances are thought to occur.

3. Strategies for the correction of disturbed NO signalling in these states are reviewed and include both prescribed pharmacological interventions, such as lipid‐lowering therapy and novel uses of angiotensin‐converting enzyme inhibitors, as well as non‐pharmacological interventions, such as exercise and dietary supplementation with l‐arginine and n‐3 polyunsaturated fatty acids.

4. In addition to a decreased production/function of NO, the possible detrimental effects of a chronic elevation in NO production in patients with liver cirrhosis, together with a novel use of antibiotics to correct this perturbation, is outlined.
ANGIOTENSIN HYPERTENSION
Authors: Blaine Edward H. , Cunningham J Thomas , Hasser Eileen M. , Dale William E. , Li Qian , Sullivan Margaret
Published: June 2007

1. One of the most important issues in the field of hypertension research centres on the therapeutic use of inhibitors of the renin‐angiotensin system (RAS). Inhibitors of the RAS have potent anti‐hypertensive effects, even in experimental models of hypertension and in human essential hypertension, where the activity of the peripheral RAS is low or normal.

2. It is suggested here that determining the mechanisms by which activation of the peripheral RAS produces hypertension will help us determine the anti‐hypertensive effects of these inhibitors in low/normal renin‐angiotensin hypertension.

3. Three hypotheses describing the hypertensive effects of angiotensin are discussed. The first hypothesis involves the direct vasoconstrictor effects of angiotensin. The second hypothesis suggests that chronic angiotensin produces hypertension by increasing Na+reabsorption leading to volume expansion and hypertension. The final hypothesis suggests that, in angiotensin‐induced hypertension, the increased Na+reabsorption is not associated with volume expansion but, rather, is associated with an increase in vascular tone resulting from an interaction between angiotensin and the nervous system.

4. It is also hypothesized that the interaction between angiotensin and the nervous system produces a differential activation of sympathetic outflow that spares the kidney.
DIFFICULTIES IN DETECTING PARATHYROID HYPERTENSIVE FACTOR IN THE RAT
Authors: Mangos George J , Brown Mark A , Whitworth Judith A
Published: June 2007

1. Parathyroid hypertensive factor (PHF) has been implicated in the pathogenesis of several forms of hypertension. We aimed to establish a PHF bioassay using spontaneously hypertensive rat (SHR) plasma.

2. Spontaneously hypertensive rats were confirmed hypertensive and their plasma was dialysed and injected into anaesthetized normotensive rats.

3. Haemodynamic responses to injected SHR plasma were uninterpretable during pentobarbital anaesthesia due to blood pressure (BP) fluctuation. Under halothane anaesthesia, BP was stable but did not rise following SHR plasma injection. Using filtered, undialysed plasma and a different brand of pentobarbital, no consistent BP response was observed following SHR plasma injection.

4. We were unable to detect PHF in the SHR.
MYOCARDIAL DYSFUNCTION IN SEPSIS
Authors: Piper Richard D
Published: June 2007

1. Sepsis is the leading reversible cause of death in patients requiring modern intensive care services.

2. In this group of patients, death usually results from progressive multiple organ failure, rather than overwhelming primary infection.

3. The pathophysiology of sepsis‐induced remote organ dysfunction is incompletely understood, although it is believed to result from a systemic inflammatory process that causes tissue injury in the absence of septic shock.

4. As septic shock is the most common early manifestation of severe sepsis, an understanding of mechanisms of myocardial dysfunction is of clinical relevance. In the present review, we will discuss mechanisms of remote organ failure in sepsis, focusing in particular on the pathogenesis of myocardial dysfunction.
META‐ANALYSIS OF NON‐RANDOMIZED COMPARATIVE STUDIES OF THE SHORT‐TERM OUTCOMES OF LAPAROSCOPIC RESECTION FOR COLORECTAL CANCER
Authors: Abraham Ned S. , Byrne Christopher M. , Young Jane M. , Solomon Michael J.
Published: June 2007

Laparoscopic resection remains to be established as the procedure of first choice for operable colorectal cancer. The aim of the study was to conduct a systematic review of non‐randomized comparative studies of laparoscopic resection for colorectal cancer. Published work in English was searched for relevant articles published by the end of 2003. The MOOSE statement was used to conduct the meta‐analysis. Study quality was assessed by two investigators using the MINORS tool and the analysis was conducted using Comprehensive Meta‐analysis software (Biostat, Englewood, NJ, USA) and Microsoft Excel (Microsoft, Redmond, WA, USA). One thousand two hundred and twenty abstracts were reviewed and 398 articles examined in detail. Out of 108 articles reporting the results of relevant studies, 75 were reports of 64 non‐randomized comparative studies. Fifteen studies were excluded. Analysis of the outcomes of 6438 resections showed that the conversion rate was 13.3% with a statistically significant difference between studies with more than 50 versus those with 50 or less attempted resections (11.7 vs 16.5%; P < 0.001). Laparoscopic resection took 27.6% (41 min) longer to carry out than open resection. There was no significant difference between the two groups in early mortality rates (1.2 vs 1.1%; P = 0.787) or likelihood of re‐operation (2.3 vs 1.5%; P = 0.319). Laparoscopic resection was associated with a lower morbidity rate (24.05 vs 30.80%, odds ratio (95% confidence interval) = 0.77 (0.63–0.95); P = 0.014, n = 4111, random‐effects model). Time until passage of first flatus, passage of a bowel motion, tolerating oral fluids and a solid diet was 1.2–1.6 days (26 to 37%) shorter, measurements of pain and narcotic analgesic requirements were 16–35% lower and hospital stay was 3.5 days (18.8%) shorter following laparoscopic resection compared with open resection. The two approaches were 99% similar in terms of adequacy of oncological clearance. Meta‐analysis of non‐randomized comparative studies favours laparoscopic over open resection for colorectal cancer. The results were remarkably similar to those of a contemporaneous meta‐analysis of randomized controlled trials published by the end of 2002.
A Kernel Variogram Estimator for Clustered Data
Authors: MENEZES RAQUEL , GARCIA‐SOIDÁN PILAR , FEBRERO‐BANDE MANUEL
Published: June 2007

Abstract. The variogram provides an important method for measuring the dependence of attribute values between spatial locations. Suppose that the nature of the sampling process leads to the presence of clustered data; it would be advisable to use a variogram estimator that aims to adjust for clustering of samples. In this setting, the use of a non‐parametric weighted estimator, obtained by considering an inverse weight to a given neighbourhood density combined with the kernel method, seems to have a satisfactory behaviour in practice. This paper pursues a theoretical study of the cluster robust estimator, by proving that it is asymptotically unbiased as well as consistent and by providing criteria for selection of the bandwidth parameter and the neighbourhood radius. Numerical studies are also included to illustrate the performance of the considered estimator and the suggested approaches.
BUSINESS TAX INTERACTIONS AMONG LOCAL GOVERNMENTS: AN EMPIRICAL ANALYSIS OF THE FRENCH CASE
Authors: Leprince Matthieu , Madiès Thierry , Paty Sonia
Published: June 2007

ABSTRACT We study the business tax (“taxe professionnelle”) behavior of the intermediate level (department) of local government in France and test in the same model the two hypotheses that department tax rates are explained by upper tier (region) tax rates and by tax rates chosen by other departments. We first reject the hypothesis of tax interactions between departments and regions, the two upper levels of local governments. Second, we provide evidence that business tax interactions among departments are significant. Including the vertical dimension in the estimated model does not lead to a decrease in the horizontal tax interactions parameter, nor to its nonsignificance.
Bioenergetic and oxidative effects of free 3‐nitrotyrosine in culture: selective vulnerability of dopaminergic neurons and increased sensitivity of non‐dopaminergic neurons to dopamine oxidation
Authors: Ma Thong C. , Mihm Michael J. , Bauer John Anthony , Hoyt Kari R.
Published: June 2007

Protein bound and free 3‐nitrotyrosine (3NT) levels are elevated in neurodegenerative diseases and have been used as evidence for peroxynitrite generation. Intrastriatal injection of free 3NT causes dopaminergic neuron injury and represents a new mouse model of Parkinson’s disease (PD). We are investigating the nature of free 3NT neurotoxicity. In primary ventral midbrain cultures, free 3NT damaged dopaminergic neurons, while adjacent non‐dopaminergic neurons were unaffected. Combined treatment with free 3NT and subtoxic amounts of dopamine caused extensive death of non‐dopaminergic forebrain neurons in culture. Free 3NT alone directly inhibited mitochondrial complex I, decreased ATP, sensitized neurons to mitochondrial depolarization, and increased superoxide production. Subtoxic concentrations of rotenone (instead of free 3NT) caused similar results. Additionally, free 3NT and dopamine combined increased extraneuronal hydrogen peroxide and decreased intraneuronal glutathione levels more than dopamine alone. Oxidative and bioenergetic processes have been proposed to contribute to neurodegeneration in PD. As free 3NT is a compound that is increased in PD, damages dopamine neurons in vivo and in vitro and has detrimental effects on neuronal bioenergetics, it is possible that free 3NT is an endogenous contributing factor to neuronal loss, in addition to being a marker of oxidative and nitrative processes.
Noradrenergic Mechanisms in Ethanol Diuresis
Authors: Pohorecky L. A. , Packard Kim
Published: June 2007

Neurotransmitter mechanisms that mediate the effect of ethanol on urine output were examined in male rats. To establish the neuronal systems involved in the diuretic action of ethanol, urine output was evaluated in animals pretreated with various pharmacological agents. The intraventricular administration of norepinephrine (1.5–12 μg) increased the diuresis produced by a 1.25 g/kg dose of ethanol. Clonidine (2.5, 5.0 μg), an α2‐receptor agonist, also increased ethanol diuresis, while the α1‐raceptor antagonist phentol‐amine (14 and 35 μg) reduced it β1,2‐Adrenergk blocker propranolol (5 and 10 μg) significantly depressed ethanol‐induced urine output Conversely the β2,2‐noradrenergic agonist isoproterenol (5 and 10 μg) increased the diuretic action of ethanol. On the other hand dopamine (4–20 μg) and serotonin (8 and 20 μg) had no effect on ethanol diuresis when given intraventriculariy. These results indicate that the diuretic action of ethanol involves noradrenergic mechanisms.
The Ferret: A New Model of Oral Ethanol Injury Involving the Liver, Bone Marrow, and Peripheral Blood Lymphocytes
Authors: Roselle Gary A. , Mendenhall Charles L. , Muhleman Albert F. , Chedid Anthony
Published: June 2007

We have developed a model of oral ethanol ingestion in the ferret by providing a complete liquid diet in which 21% of the total caloric intake is given as ethanol. After 3 weeks of ethanol treatment, migration inhibitory factor activity from ferret lymphocytes was significantly decreased when compared to animals fed a dextrose‐substituted, identical liquid diet Lymphocyte blastogenesis in response to the mitogen, phytohemagglutinin, was also decreased after 6 weeks of ethanol ingestion. Histopathologically, hepatic cell degeneration, fat deposition, and “Mallory body‐like” material were present after 11 weeks of therapy. Bone marrow aspirate cells from the iliac crest of ethanol‐fed animals showed vacuolization in both erythroid and myeloid elements after 6 weeks of ethanol ingestion. Mean ferret weights were not significantly different between the ethanol and dextrose control groups; serum ethanol and acetalde‐hyde concentrations were somewhat higher over the study period compared to those seen in human alcoholics. Therefore, we have designed a small animal model of the toxic effects of alcohol in which multiple organ systems exhibited evidence of ethanol‐reiated disease.
Drinking Behavior of High Risk College Men: Contradictory Preliminary Findings
Authors: Alterman Arthur I. , Bridges K. Robert , Tarter Ralph E.
Published: June 2007

Seventeen high risk and seventeen low risk college‐aged men were compared with respect to drinking behavior/problems and certain implicated personality characteristics. The low risk subjects were, surprisingly, found to drink and become intoxicated more frequently than high risk subjects. They also reported significantly higher sensation seeking scores. This latter variable accounted for the greatest amount of variance in both risk status and frequency of drinking. By contrast, high risk subjects reported somewhat more lifetime alcohol‐related symptomatology and significantly more preaduK antisocial symptoms. Preadult antisocial symptoms, alone, explained 39% and 29%, respectively, of the variance in alcohol‐related symptoms and the amount consumed on a typical drinking day. The implications and limitations of the findings with respect to the development of alcoholism are discussed.
Initiation of Ethanol Reinforcement using a Sucrose‐Substitution Procedure in Food‐ and Water‐Sated Rats
Authors: Samson Herman H.
Published: June 2007

Rats, maintained on free access to both food and water, were trained to press a lever to obtain a 20% sucrose solution. When presentation of the sucrose solution was maintaining responding, low ethanol concentrations were added to the solution. Over 25 sessions, the solution presented as reinforcement was gradually reduced in sucrose concentration until a 10% ethanol solution with no sucrose was presented. Following this initiation procedure, ethanol concentrations up to and including 40% ethanol were found to maintain responding. At the higher ethanol concentrations, the rats consumed doses of ethanol between 0.90 and 0.95 g/kg in the 30‐min session. When a concurrent choice between ethanol and water was available in the operant chamber, the rats responded on the lever associated with 10% ethanol presentation. Home cage preference between ethanol and water was found to be altered following the operant ethanol experience with the rats acceptability for 10% ethanol increased prior to the start of the experiment This initiation procedure provides another manner in which ethanol reinforcement can be instigated in animals that have not been either food‐ or fluid‐deprived. It is hypothesized that mechanisms which may regulate the intravascular and intragastric self‐administration of ethanol may also be operating when the oral route is employed.
Increased Vitamin A in Esophagus and Other Extrahepatic Tissues after Chronic Ethanol Consumption in the Rat
Authors: Leo Maria Anna , Kim Cho‐il , Lieber Charles S.
Published: June 2007

In rats fed ethanol (36% of total energy) for 1 month, vitamin A content of the esophageal mucosa was found to be increased 5‐fold, compared to animals pair‐fed an isocatoric control diet containing the same amount of vitamin A. Similar results were observed with diets of either lower vitamin A content or zinc supplementation. Significant increases of retinoids were also found in lungs, trachea, kidneys, and testes, but not in the eyes. These increases in extra‐hepatic tissues contrasted strikingly with the concomitant decrease in the liver and suggests that chronic ethanol consumption may be associated with some mobilization of vitamin A from the liver to other organs.
Alcohol Consumption, Blood Pressure, Lipids, and Cardiovascular Mortality
Authors: Criqui Michael H.
Published: June 2007

Interest in the effects of alcohol on cardiovascular risk factors and disease has increased sharply with reports of complex and previously unsuspected associations. The present report focuses on the associations of alcohol with blood pressure, lipids, and cardiovascular disease mortality. The epidemiological evidence to date appears to support the idea that moderate alcohol consumption, defined as two drinks a day or less, may offer some protection for coronary heart disease, but that higher levels of alcohol promote hypertension and are directly toxic to the heart, leading to stroke, arrhythmias, cardiomyopathy, and perhaps even coronary heart disease.
Increased Monoester Lipase Activity of Red Blood Cells in Alcoholism
Authors: DelpéAro Claude , Gastakji Marguerite , Vérine Alain , Campistron Marcel , Boyer Jean
Published: June 2007

Monoester lipase activity was assayed by a radiochemical assay in the red blood ceHs (RBC) from 50 chronic alcoholic patients within 48 hr after discontinuation of chronic alcohol intake and from 40 nonalcoholic control subjects. The mean value of lipase activity was increased to 1213 ± 229 miWunits/1013 RBC in the alcoholics as compared with a value of 997 ± 120 milliunits/1012 RBC in the controls (p < 0.001). The lipase increase was associated with increased values of the mean cellular volume of RBC. A subgroup (64%) of 32 alcoholic lubjocti with macrocytosis (mean cellular volume > 96 femtoHters) showed the highest mean lipase activity (1276 ± 224 mtthuntts/1012 RBC) as compared with a value of 1101 ± 196 milli‐unrts/1012 RBC in the normocyte alcoholic subgroup (p < 0.05). This latter subgroup had a mean value higher (p < 0.05) than that in the control group. The relationship between values of mean ceHular volume and lipase activity was not of predictive value in individual cases. The enzymatic increase was not related to a direct effect of alcohol on the Intact RBC. It is postulated that this alteration might result from changes in the chemical and/or physical state of the plasma membrane induced by ethanol during RBC formation. In any event, the increased lipolytic activity of RBC represents a new biological characteristic of alcoholic subjects. Its determination might represent a noninvasive way of evaluating the influence of alcohol on a tissue parameter.
Suicide in Male Alcoholics with Peptic Ulcers
Authors: Berglund Mats
Published: June 2007

Eighty‐seven male alcoholics with peptic ulcers and 913 without peptic ulcers were first admitted to the Department of Psychiatry of Lund, Sweden during the period 1956–1969. In the initial ratings rigidity/perfectionism, strain/tenseness, sleep disturbances, the asthenic syndrome, and heredity for alcoholism/personality disturbances/suicide were more frequent in the peptic ulcer group than in the others. Patients with peptic ulcers were more often married and less often unmarried or showed antisocial/criminal indications of antisocialrty/criminality. A follow‐up by records was performed on January 1, 1981. Seventeen percent in the peptic ulcer group and 6% in the other group had committed suicide (p < 0.001). Mortality (suicides excluded) was similar in the two groups as was the social adjustment among the survivors. Within the peptic ulcer group strain/ tenseness was significantly related to future suicide, while operation, heredity, and rigidity/perfectionism were not.
Plasma Fatty Acid Pattern Including Diene‐Conjugated Linoleic Acid in Ethanol Users and Patients with Ethanol‐Related Liver Disease
Authors: Szebeni J. , Esketson C. , Sampliner R. , Hartmann B. , Griffin J. , Dormandy T. , Watson Ronald Ross
Published: June 2007

The level of conjugated dienes (CO) in the serum, conjugated linoleic acid isomer in the phospholipid fraction [18:2(9,11)], and the fatty acid profile in both the serum and in the separated lipid classes were analyzed in current and previous alcohol abusers and in patients with alcoholic liver disease. None of the subjects consumed alcohol for at least 2–3 days prior to blood collection for analysis of lipids. There was no significant difference in CD or in the absolute level of 18:2(9,11) among the groups, whereas the 18:2(9,11)/ 18:2(9,12) molar ratio was significantly elevated in patients with liver disease. Fatty acid analysis of the whole plasma extract showed that the absolute level of arachidonic acid increased from 4.8 ± 3.5 mg/dl (n= 9) in lifelong abstainers to 13.4 ± 4.0 (n= 8) in current ethanol abusers, and its relative level (related to the total fatty acids) from 1.73 ± 1.34 to 4.55 ± 1.01 in the same groups. An increased proportion of linoleic acid in the triglyceride and phospholipid fractions from current abusers and patients with liver disease was also found; the percentage of 18:2 in phospholipids increased from 5.4 ± 5.0 (n = 8) in lifelong abstainers to 14.3 ± 3.9 (n = 8) in current abusers and 12.7 ± 2.2 (n = 10) in patients with Hver disease. The percentage of 16:0 was significantly lower in the phospholipids of current abusers as compared to lifelong abstainers. These data confirm earlier findings on increased free radical activity in liver diseases, and a lack of it in chronic alcoholics (unless they consume alcohol 1–2 days before the test). The fatty add profiles suggest a relative accumulation of long chain fatty acids induced by ethanol, conceivably due to a differential effect of ethanol on the β‐oxidation and esterificatjon of fatty acids according to their chain length. The observed changes may be useful in biochemical diagnosis of alcohol use.