Sympathetic nerve regulation of cochlear blood flow during increases in blood pressure in humans

The purpose of this work was to show that regulation of the blood flow to the cochlea by the sympathetic nervous system occurs in humans at the level of the cochlear microcirculation during increases in blood pressure and that its involvement depends on the pressure level. Eight anaesthetized patients undergoing tympanoplasty for hearing disease took part in a pharmacological protocol of stimulation and inhibition of the autonomic nervous system (ANS) to provide variations in systolic blood pressure (BP_S) and cochlear blood flow (CBF). The CBF was measured by laser-Doppler flowmetry. Changes in autonomic nerve activity were brought about by changes in baroreceptor activity (BR) initiated by the injection of an α adrenergic agent before and after sympathetic and parasympathetic blockade. The CBF variations (δCBF) were plotted against BP_S increases at each stage of the ANS inhibition. The BR diminished significantly after α blockade, after α and β blockade, and after α and β blockade and atropine, by 50% (P < 0.01), 29% (P < 0.05), and 95% (P < 0.001) respectively. The BP_S increased significantly (P < 0.01) by 36 (SD 9)%, 47 (SD 1)%, and 67 (SD 16)% respectively. The CBF response to an increase in BP_S exhibited two opposing variations in the patients: CBF decreased significantly in one group, and increased significantly in the other group. In both groups, δCBF decrease and δCBF increase, respectively, were significant after ANS blockade; even so the decrease and increase, respectively, levelled off at BP_S around 160 mmHg before ANS blockade. For BP_S below 160 mmHg, correlations between δCBF and BP_S were significant before inhibition and after inhibition of ANS. For BP_S above 160 mmHg, BP_S and δCBF were not correlated before inhibition of ANS, and were significantly correlated after inhibition of ANS. For BP_S below 160 mmHg, CBF response to the BP_S increase was the same before and after ANS blockade, i.e. ANS control did not predominate; even so, for BP_S above 160 mmHg, the CBF response to BP_S increase was different before and after ANS blockade: CBF varied significantly after ANS blockade as it varied for BP_S below 160 mmHg, while it remained constant before ANS blockade that elicited ANS control of CBF. In conclusion, sympathetic nerve regulation via its vasomotor tone at the level of cochlear microcirculation occurred markedly when the blood pressure was above 160 mmHg; the autonomic nervous system would appear to control the cochlear blood flow against large variations in blood flow in response to hypertensive phenomena. Accepted: 7 October 1996     

A literature review: the effects of magnetic field exposure on blood flow and blood vessels in the microvasculature

The effect of magnetic field (MF) exposure on microcirculation and microvasculature is not clear or widely explored. In the limited body of data that exists, there are contradictions as to the effects of MFs on blood perfusion and pressure. Approximately half of the cited studies indicate a vasodilatory effect of MFs; the remaining half indicate that MFs could trigger either vasodilation or vasoconstriction depending on initial vessel tone. Few studies indicate that MFs cause a decrease in perfusion or no effect. There is a further lack of investigation into the cellular effects of MFs on microcirculation and microvasculature. The role of nitric oxide (NO) in mediating microcirculatory MF effects has been minimally explored and results are mixed, with four studies supporting an increase in NO activity, one supporting a biphasic effect, and five indicating no effect. MF effects on angiogenesis are also reported: seven studies supporting an increase and two a decrease. Possible reasons for these contradictions are explored. This review also considers the effects of magnetic resonance imaging (MRI) and anesthetics on microcirculation. Recommendations for future work include studies aimed at the cellular/mechanistic level, studies involving perfusion measurements both during and post-exposure, studies testing the effect of MFs on anesthetics, and investigation into the microcirculatory effects of MRI.     

Sensory modulation and behavioral choice during feeding in the Australian frog, Cyclorana novaehollandiae

This study investigates how visual and tactile sensory information, as well as biomechanical effects due to differences in physical characteristics of the prey, influence feeding behavior in the frog Cyclorana novaehollandiae. Video motion analysis was used to quantify movement patterns produced when feeding on five prey types (termites, waxworms, crickets, mice and earthworms). Twelve kinematic variables differed significantly among prey types, and twelve variables were correlated with prey characteristics (including mass, length, height and velocity of movement). Results indicate that C.␣novaehollandiae uses a different strategy to capture each prey type. Visual assessment of prey characteristics appeared to be more important in modulating feeding behavior than tactile cues or biomechanical effects. We propose a hierarchical hypothesis of behavioral choice, in which decisions are based primarily on visual analysis of prey characteristics. In this model, the frogs first choose between jaw prehension and tongue prehension based on prey size. If they have chosen jaw prehension, they next choose between upward or downward head rotation based on length and height of the prey. If they have chosen tongue prehension, they next choose between behavior for fast and slow prey. Final decisions may be the result of behavioral fine tuning based on tactile feedback. Accepted: 5 August 1996     

Effects of feeding and hypoxia on cardiac performance and gastrointestinal blood flow during critical speed swimming in the sea bass Dicentrarchus labrax

Previous studies have shown that if European sea bass are exercised after feeding, they can achieve a significantly higher maximum metabolic rate (MMR) than when fasted. They can meet combined metabolic demands of digestion (specific dynamic action, SDA) and maximal aerobic exercise, with no decline in swimming performance. If, however, exposed to mild hypoxia (50% saturation), bass no longer achieve higher MMR after feeding but they swim as well fed as fasted, due to an apparent ability to defer the SDA response. This study explored patterns of cardiac output (Q_A) and blood flow to the gastrointestinal tract (Q_GI) associated with the higher MMR after feeding, and with the ability to prioritise swimming in hypoxia. Sea bass (mean mass ~ 325 g, forklength ~ 27 cm) were instrumented with flow probes to measure Q_A and Q_GI during an incremental critical swimming speed (U_crit) protocol in a tunnel respirometer, to compare each animal either fasted or 6 h after a meal of fish fillet equal to 3% body mass. Feeding raised oxygen uptake (M_O2) prior to exercise, an SDA response associated with increased Q_A (+ 30%) and Q_GI (+ 100%) compared to fasted values. As expected, when exercised the fed bass maintained the SDA load throughout the protocol and achieved 14% higher MMR than when fasted, and the same U_crit (~ 100 cm s^-1). Both fed and fasted bass showed pronounced increases in Q_A and decreases in Q_GI during exercise and the higher MMR of fed bass was not associated with higher maximum Q_A relative to when fasted, or to any differences in Q_GI at maximum Q_A. In hypoxia prior to exercise, metabolic and cardiac responses to feeding were similar compared to normoxia. Hypoxia caused an almost 60% reduction to MMR and 30% reduction to U_crit, but neither of these traits differed between fed or fasted bass. Despite hypoxic limitations to MMR and U_crit, maximum Q_A and patterns of Q_GI during exercise in fasted and fed bass were similar to normoxia. Estimating GI oxygen supply from Q_GI indicated that the ability of bass to prioritise aerobic exercise over SDA when metabolically limited by hypoxia was linked to an ability to defer elements of the SDA response occurring outside the GI tract.     

Comparative physiology and molecular analysis of carbonic anhydrase from the red blood cells of teleost fish

This study investigates the early evolution of vertebrate red blood cell (rbc) carbonic anhydrase (CA) by examining the physiological and molecular properties of rbc CA in teleost fish. When representatives of four different families of teleosts were compared, it was found that differences in overall rbc CA activity were due to different concentrations of CA, rather than differences in the enzymes kinetic properties. Additional molecular analysis of CA from the rbcs of rainbow trout provided further evidence that critical elements of the enzyme, such as the active site, have been highly conserved during vertebrate evolution. The active site of the trout CA differed from that of gar rbc CA at only two amino acid positions. The rainbow trout rbc CA sequence also showed high sequence homology with CA sequences from other fish tissues, and fits into an emerging group of fish CAs that are basal to mammalian CA I, II and III. Northern blot analysis of the tissue expression of the sequenced CA indicated that it is primarily found in the rbcs, but high amounts of cytosolic CA activity were also found in the gill, suggesting the presence of other cytosolic CA isozymes in this species.Abbreviations Az acetazolamide - CA carbonic anhydrase - MP maximum parsimony - NJ neighbour joining - RACE rapid amplification of cDNA ends - rbc red blood cellCommunicated by L.C.-H. Wang     

Effect of acetazolamide on cerebral blood flow and tympanic temperature in healthy subjects and patients with subacute subarachnoid haemorrhage

The influence of the increased cerebral blood flow (CBF) induced by acetazolamide on tympanic temperature (T _ty) was examined in three healthy male volunteers and in five patients with subacute subarachnoid haemorrhage (SAH). The CBF was estimated by means of stable xenon-enhanced computed tomography before and after the administration of acetazolamide. The T _ty was recorded continuously in both ears using thermistor thermometers. In all subjects, CBF increased ranging from 11% to 108% after acetazolamide administration. In all the healthy subjects and in two patients with mild SAH, T _ty was higher than the oesophageal temperature (T _oes) and T _ty decreased bilaterally, ranging from 0.07 to 0.35°C as CBF increased. Three patients with severe SAH were febrile, their T _oes exceeding T _ty, and their T _ty rose by 0.30 to 0.53°C with increased CBF. These observations suggest that T _ty follows brain temperature which changes with an increase in CBF in euthermic subjects as well as in febrile subjects. Accepted: 3 September 1996     

Effects of haemoglobin O2 saturation on volume regulation in adrenergically stimulated red blood cells from the trout, Oncorhynchus mykiss

Adrenergic stimulation of trout red blood cells activates a Na⁺/H⁺-exchange. If unopposed, the ensuing increase in cell Na⁺ leads to an isosmotic cell swelling. In this study the effect of the level of haemoglobin O₂ saturation on volume regulation has been investigated in adrenergically stimulated red blood cells from trout: at full haemoglobin O₂ saturation, net influx of Na⁺ through the Na⁺/H⁺-exchanger was balanced by net efflux of K⁺ and no increases in cell volume took place. In contrast, at low O₂ saturation (8–14%) adrenergic stimulation led to a substantial increase in cell Na⁺, K⁺ and volume. Moreover, cell volume recovery after adrenergic swelling was incomplete at low O₂ saturation, whereas cells at high O₂ saturation exhibited a fast and complete cell volume recovery. In cells exposed to alternating high and low O₂ saturation, volume regulation was similar to the regulation found in cells maintained at high O₂ saturation. In cells at high O₂ saturation, extrusion of cellular Na⁺ by the Na⁺/K⁺-pump significantly contributed to the volume decrease. It is concluded that trout red blood cells at high or alternating O₂ saturations possess a powerful regulatory volume decrease response that is shut off at low O₂ saturation. The physiological implications of this regulation is discussed. Accepted: 30 September 1996     

A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs

The endogenous peptides somatostatin and secretin are effective in the therapy of upper gastrointestinal tract bleeding and acute pancreatitis. The clinical effects may be partly brought about by changes in the regional blood flow. To evaluate the effects of somatostatin (50 and 100 μg/min over 6–8 min) and secretin (0.1 and 0.5 U · kg^?1 · min^?1 over 3–5 min) on tissue blood flow, particularly of the gastrointestinal tract, the tracer microsphere reference sample method was used in anesthetized dogs.Infusion of somatostatin significantly diminished gastric and pancreatic blood flow whereas no changes of duodenal and ileal blood flow could be obtained. Blood flow through spleen, kidneys and adrenal glands was increased but no changes were observed in the blood flow of other tissues. Cardiac hemodynamics remained unchanged.Secretin increased the blood flow of the duodenum, the kidneys and the adrenal glands and diminished gastric blood flow without changing pancreatic, ileal, hepatic, pulmonary and muscle blood flow. Cerebral, pituitary and myocardial blood flow was increased by a higher dose of secretin. It also evoked a slight but significant positive ino- and chronotropic effect. Since secretin and somatostatin differ in their respective effects on gastrointestinal blood flow it is suggested that the previously reported beneficial effects of both peptides on upper gastrointestinal bleeding cannot solely be attributed to changes in regional blood flow.     

Daily rhythms of serum leptin in ewes: effects of feeding, pregnancy and lactation

The aim of the present study was to test whether serum concentrations of leptin in ewes vary with a daily rhythm. For this purpose, we examined 24 h serum leptin profiles of ewes exposed to natural photoperiodic conditions and subjected to two different feeding schedules (regular feeding and fasting). The results show for the first time the existence of daily rhythm of plasma leptin in regularly fed ewes, with a minimum during the light phase and a peak during the dark phase. Daily rhythms of serum leptin persisted after 50 h of fasting, although fasting shifted the peak of the rhythm to the beginning of the light phase and significantly reduced daily leptin production. To gain a better understanding of the role of leptin in the temporal organization of physiological events related to pregnancy and lactation, we measured serum leptin profiles throughout 24 h in ewes either during pregnancy or lactation. Daily leptin rhythms were found to persist during pregnancy and lactation, but both physiological conditions altered leptin concentrations. Maternal serum leptin concentration rose between early and mid pregnancy, then decreased in the late pregnancy and during lactation. Daily serum leptin concentration was significantly lower in nonpregnant, nonlactating ewes, compared either to lactating or to early pregnant ewes.     

The heat increment of feeding in house wren chicks: magnitude, duration, and substitution for thermostatic costs

The heat increment of feeding (HIF), a transient postprandial increase in metabolic rate, is the energy cost of processing a meal. We measured HIF in house wren chicks (Troglodytes aedon) ranging in mass from 1.6 to 10.3 g. This mass range (age 2–10 days) spanned a transition from blind, naked, ectothermic chicks through alert, endothermic birds with nearly complete feathering. We fed chicks crickets (2.7–10% of chick body mass) and determined HIF from continuous measurements of oxygen consumption rate (O₂) before and after meals. At warm ambient temperatures (T _a) of 33–36 °C, the magnitude of HIF (in ml O₂ or joules) was linearly related to meal mass and was not affected by chick mass. HIF accounted for 6.3% of ingested energy, which is within the range of results for other carnivorous vertebrates. The duration of HIF was inversely related to chick mass; 10-g chicks processed a standard meal approximately twice as fast as 2-g chicks. HIF duration increased with increasing meal mass. The peak O₂ during HIF, expressed as the factorial increase above resting metabolism, was independent of body mass and meal mass. In large, endothermic chicks ( > 8 g), HIF substituted for thermoregulatory heat production at low T _a. Accepted: 11 December 1996     

Protective effects of GSH,vitamin E,and selenium on lipid peroxidation in cadmium-fed rats

Increased intake of Cd results in its retention and in peroxidative damage in soft tissues. Coadministration of antioxidants, viz., glutathione (GSH), α-tocopherol, and Se, restricted the uptake and distribution of Cd in liver and kidney of rats. Moreover, no rise in malondialdehyde was recorded. Although possible antioxidative mechanisms manifested by GSH, α-tocopherol, and Se have been discussed, it is hypothesized that GSH functions as a Cd chelator. Glutathione yielded favorable effects in comparison to Se and α-tocopherol.     

Antitumor effects of the combination immunotherapy with interleukin-12 and tumor necrosis factor α in mice

 There is strong evidence that antitumor activity of interleukin-12 (IL-12) in vivo is mediated, in part, through interferon (IFNγ) produced by IL-12-stimulated natural killer and T cells. Since IFNγ and tumor necrosis factor α (TNFα) have been reported to synergize in antitumor effects in a number of models, we decided to examine whether the combined treatment with recombinant mouse IL-12 and recombinant human TNFα would produce similar effects. The efficacy of the combined IL-12/TNFα immunotherapy was evaluated in three tumor models in mice: B16F10 melanoma, Lewis lung (LL/2) carcinoma and L1 sarcoma. Intratumoral daily injections of 1 μg IL-12 in combination with 5 μg TNFα into B16F10-melanoma-bearing mice resulted in a significant retardation of the tumor growth as compared with that in controls and in mice treated with either cytokine alone. Similar effects were obtained using 0.1 μg IL-12 and 5 μg TNFα in LL/2 carcinoma and L1 sarcoma models. Antitumor activity against L1 sarcoma was still preserved when TNFα at a low dose (1 μg) was combined with 0.1 μg IL-12 and applied for a prolonged time. Potentiation of antitumor effects, which was observed in IL-12/TNFα-based immunotherapy, could result from at least three different mechanisms, partly related to stimulation of IFNγ and TNFα production in treated mice: (a) direct cytostatic/cytotoxic effects on tumor cells, (b) induction of antitumor activity of macrophages, and (c) inhibition of blood vessel formation in the tumor. Our studies demonstrate that combination tumor immunotherapy with IL-12 and TNFα may be more effective than single-cytokine treatment, and suggest possible mechanisms by which IL-12 and TNFα may exert potentiated therapeutic effects against locally growing tumors. Received: 17 February 1997 / Accepted: 5 August 1997     

Absence of adrenergic red cell pH and oxygen content regulation in American eel (Anguilla rostrata) during hypercapnic acidosis in vivo and in vitro

Summary American eels (Anguilla rostrata) were exposed to acute (30 min) external hypercapnia (1% CO₂ or 5% CO₂ in air) in order to assess the involvement of circulating catecholamines in regulating red blood cell (RBC) pH and oxygen content during whole blood acidosis. Plasma adrenaline levels increased approximately 5-fold during severe hypercapnia yet absolute levels remained below 1.0 nM; plasma noradrenaline levels were unchanged. Both RBC pH and oxygen bound to haemoglobin ([O₂]/[Hb]) conformed to in vitro relationships with whole blood pH (pHe) indicating absence of regulation during hypercapnia in vivo. Pre-treatment of eels with - or -adrenoceptor antagonists, phentolamine or propranolol was without effect on RBC pH or [O₂]/[Hb] during hypercapnia. Further, intra-arterial injection of adrenaline (final plasma concentration=134 nM) or noradrenaline (final plasma concentration = 34 nM) into hypercapnic eels 5 min prior to blood sampling did not modify any measured blood variable RBC nucleoside triphosphate (NTP) levels, RBC pH and [O₂]/[Hb]. In vitro, the application of adrenaline or noradrenaline to eel RBC's during graded normoxic hypercapnia or hypoxic hypercapnia (noradrenaline only) did not affect RBC pH significantly. RBC NTP levels were depressed by noradrenaline in vitro but only during hypoxic hypercapnia.The results demonstrate adrenergic insensitivity of eel RBC's in vivo even under conditions (acidosis, hypoxemia) known to enhance catecholamine-mediated RBC responses in other species. We conclude that the American eel has no capacity to regulate RBC pH during hypercapnia and consequently [O₂]/[Hb] is reduced in accordance with the in vitro Root effect.     

Characterization of OsPID, the rice ortholog of PINOID, and its possible involvement in the control of polar auxin transport

PINOID, a serine threonine protein kinase in Arabidopsis, controls auxin distribution through a positive control of subcellular localization of PIN auxin efflux carriers. Compared with the rapid progress in understanding mechanisms of auxin action in dicot species, little is known about auxin action in monocot species. Here, we describe the identification and characterization of OsPID, the PINOID ortholog of rice. Phylogenetic analysis showed that the rice genome contains a single PID ortholog, OsPID. Constitutive overexpression of OsPID caused a variety of abnormalities, such as delay of adventitious root development, curled growth of shoots and agravitropism. Abnormalities observed in the plants that overexpress OsPID could be phenocopied by treatment with an inhibitor of active polar transport of auxin, indicating that OsPID could be involved in the control of polar auxin transport in rice. Analysis of OsPID mRNA distribution showed a complex pattern in shoot meristems, indicating that it probably plays a role in the pattern formation and organogenesis in the rice shoot.     

Electroencephalograms and cerebral blood flow in carp, Cyprinus carpio, subjected to acute hypoxia

Changes in electroencephalogams (EEG) and cerebral blood flow were examined in carp immobilized with a muscle relaxant during 60 min hypoxia (water Po ₂ of approximately 20 mmHg) and subsequent 30 min normoxia. The amplitude of EEG waves recorded from the telencephalon decreased gradually but slightly with the progression of hypoxia, whereas the telencephalic blood flow increased mainly due to an increased blood velocity. These findings suggested that cerebral activity during hypoxia was compensated to some degree by increased cerebral blood flow. However, carp showed large variations in the patterns of EEG responses and cerebral blood flow.     

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells

Antioxidant phytochemicals are investigated as novel treatments for supportive therapy in β-thalassemia. The dietary indicaxanthin was assessed for its protective effects on human β-thalassemic RBCs submitted in vitro to oxidative haemolysis by cumene hydroperoxide. Indicaxanthin at 1.0-10 μM enhanced the resistance to haemolysis dose-dependently. In addition, it prevented lipid and haemoglobin (Hb) oxidation, and retarded vitamin E and GSH depletion. After ex vivo spiking of blood from thalassemia patients with indicaxanthin, the phytochemical was recovered in the soluble cell compartment of the RBCs. A spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb generated in solution from met-Hb and hydrogen peroxide (H₂O₂), more effectively than either Trolox or vitamin C.

Collectively our results demonstrate that indicaxanthin can be incorporated into the redox machinery of β-thalassemic RBC and defend the cell from oxidation, possibly interfering with perferryl-Hb, a reactive intermediate in the hydroperoxide-dependent Hb degradation. Opportunities of therapeutic interest for β-thalassemia may be considered.     

Genetic linkages of the circadian clock-associated genes, TOC1, CCA1 and LHY, in the photoperiodic control of flowering time in Arabidopsis thaliana

In Arabidopsis thaliana, the flowering time is regulated through the circadian clock that measures day-length and modulates the photoperiodic CO-FT output pathway in accordance with the external coincidence model. Nevertheless, the genetic linkages between the major clock-associated TOC1, CCA1 and LHY genes and the canonical CO-FT flowering pathway are less clear. By employing a set of mutants including an extremely early flowering toc1 cca1 lhy triple mutant, here we showed that CCA1 and LHY act redundantly as negative regulators of the photoperiodic flowering pathway. The partly redundant CCA1/LHY functions are largely, but not absolutely, dependent on the upstream TOC1 gene that serves as an activator. The results of examination with reference to the expression profiles of CO and FT in the mutants indicated that this clock circuitry is indeed linked to the CO-FT output pathway, if not exclusively. For this linkage, the phase control of certain flowering-associated genes, GI, CDF1 and FKF1, appears to be crucial. Furthermore, the genetic linkage between TOC1 and CCA1/LHY is compatible with the negative and positive feedback loop, which is currently believed to be a core of the circadian clock. The results of this study suggested that the circadian clock might open an exit for a photoperiodic output pathway during the daytime. In the context of the current clock model, these results will be discussed in connection with the previous finding that the same clock might open an exit for the early photomorphogenic output pathway during the night-time.     

The interaction of thin-film flow, bacterial swarming and cell differentiation in colonies of Serratia liquefaciens

 The rate of expansion of bacterial colonies of S. liquefaciens is investigated in terms of a mathematical model that combines biological as well as hydrodynamic processes. The relative importance of cell differentiation and production of an extracellular wetting agent to bacterial swarming is explored using a continuum representation. The model incorporates aspects of thin film flow with variable suspension viscosity, wetting, and cell differentiation. Experimental evidence suggests that the bacterial colony is highly sensitive to its environment and that a variety of mechanisms are exploited in order to proliferate on a variety of surfaces. It is found that a combination of effects are required to reproduce the variation of bacterial colony motility over a large range of nutrient availability and medium hardness. Received: 29 April 1999