bluuebunny/crossref_metadata_2025 huggingface dataset:
Villus tip microcirculation in the rat duodenum
Authors: SABABI M. , HOLM L.
Published: December 2008

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rev) in capillaries in the tip of duodenal villi and by laser‐Doppler flowmetry (LDF). Rev increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by ∼ 10% of the blood volume) reduced rev in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rev in the villus capillaries exposed to abdominal Po2 (∼ 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension.

In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.
Mitochondrial ATP production rate in 55 to 73‐year‐old men: effect of endurance training
Authors: BERTHON P. , FREYSSENET D. , CHATARD J.‐C. , CASTELLS J. , MUJIKA I. , GEYSSANT A. , GUEZENNEC C.‐Y. , DENIS C.
Published: December 2008

The effect of 6‐week endurance training on mitochondrial ATP production rate was investigated in 14 elderly men. Mean age, body weight and height were 63±6yr, 75.6 ± 9.2 kg and 174±4cm, respectively. Subjects trained on a Monark cycle ergometer at 79 ± 8% of their maximal heart rate for 1 h day‐1, 4 days week‐1. Muscle samples were obtained at rest, before and after endurance training, by a needle biopsy technique and used for determination of mitochondrial ATP production rate in isolated mitochondria and enzyme assays. Endurance training resulted in a significant increase in maximal oxygen uptake (L min‐1) (P < 0.01). Citrate synthase activity, a mitochondrial marker enzyme, and hexokinase activity increased significantly (both P < 0.01) in response to training while 3‐hydroxyacyl‐CoA dehydrogenase and carnitine palmitoyltransferase I activities remained statistically unchanged. A higher mitochondrial ATP production rate was observed after endurance training with the substrate combinations pyruvate ± palmitoyl‐L‐carnitine + L‐glutamate + malate (P < 0.01), L‐glutamate (P < 0.001), pyruvate + malate (P < 0.05) and palmitoyl‐L‐carnitine + malate (P < 0.01). The largest increase was obtained with L‐glutamate (170%). Significant correlations were observed between the percent increase in citrate synthase activity and those of mitochondrial ATP production rates. It was concluded that the increased mitochondrial ATP production rate of aged human skeletal muscle with training seems mainly to occur through an increased mitochondrial content, and in a way similar to those observed in young men.
Protein loss and capillary protein permeability in dependent regions upon quiet standing
Authors: BJERKHOEL P. , LINDGREN P. , LUNDVALL J.
Published: December 2008

Seven healthy males were exposed to quiet standing (15 min) after supine rest. Alterations in the total mass of plasma proteins were analysed from changes in plasma volume (PV; determination of control PV and subsequently of induced per cent PV changes using Hb/Hct) and protein concentration as revealed in arterial blood collected after standing. This approach adopted the concept that valid data on overall circulatory haemoconcentrations prevailing on standing can only be reached when blood is sampled on resumption of the recumbent posture, whereas conventional sampling from the standing subject provides erroneous information. The PV reduction on standing averaged 649 ± 65 mL (16.9 ± 1.0%). There were very similar net decreases in plasma (serum) total protein (7.6 ± 0.8 g) and albumin (7.8 ± 0.9 g). These findings permitted the following main conclusions of physiological and methodological pertinence: (1) Quiet standing leads to a clear‐cut net decrease in the plasma protein content predominantly confined to albumin, in all probability via convection secondary to PV loss by filtration in dependent regions. (2) It is suggested that the albumin loss reflects a quite high capillary macromolecular permeability in the dependent limbs on standing preferentially confined to skin/subcutaneous tissues. (3) The albumin loss implies that plasma concentration changes of neither albumin nor of total protein can be used to describe the PV loss on standing. However, concentration changes of the plasma globulin fraction as a whole, expressed by the difference (total protein –albumin), seem to reflect PV alterations approximately.
Effect of verapamil on restoration of cardiac performance in raised [K+]0by adrenergic stimulation in the rabbit
Authors: NEILL M. O.' , RYAN D. M. , PATERSON D. J.
Published: December 2008

Modulation of the L‐type calcium channel by catecholamines improves action potential parameters in single ventricular myocytes depolarized by high [K+]0Tyrode. Whether this modulation is important in offsetting the negative effects of hyperkalaemia in the whole heart is not known. We tested the effects of the calcium channel antagonist, verapamil, on restoration of cardiac performance by adrenergic stimulation in high [K+]0in anaesthetized rabbits and isolated perfused working rabbit hearts. Raised [K+]0decreased SBP, LVP and LVdP/dtmaxin vivo([K+]a8.6 ± 0.2 mM;n= 10) and aortic flow (AF) in the isolated heart (8 mM [K+]0Tyrode;n= 25). However, the negative effects of raised [K+]awere offset by isoprenaline (Iso, 1 μg kg‐1min‐1i.v.)in vivoand by noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg‐1iv.; 15 nM isolated heart) markedly potentiated the negative inotropic effects of raised [K+]nin both preparations. Verapamil attenuated the effect of isoprenalinein vivobut in the isolated heart, the protective effect of NA in 8 mM [K+] Tyrode (AF 97 ± 10 mL min1in 8 mM [K+]0compared with AF 141 ± 8.5 mL min‐1in 8 mM [K+]0+ NA) was offset by the drug (90±8mL min‐1in 8 mM [K+]0+ NA + V). Furthermore, verapamil abolished aortic flow in 8 mM [K+]0alone. These findings suggest that the heart may be critically dependent on modulation of intracellular calcium in order to tolerate concentrations of K4similar to those seen during a short burst of intensive exercise ([K+]a8.6 mM).
ERG OFF response in frog retina: light adaptation and effect of 2‐amino‐4‐phosphonobutyrate
Authors: POPOVA E. , KUPENOVA P. , VITANOVA L. , MITOVA L.
Published: December 2008

The intensity‐response (V/log I) function of ERG OFF response (d‐wave) in dark and light adapted superfused frog eyecups was investigated before and after blockade of the retinal ON channel by 2‐amino‐4‐phosphonobutyrate (APB). The V/logI function of the dark adapted d‐wave had two distinct components, each of them consisting of an ascendent and descendent part. In eyes adapted to mesopic or photopic background the V/log I function had only one component. It was shifted to the right along the intensity axis, had a steeper slope and a higher maximal response amplitude compared with the two components of the dark‐adapted V/log I curve.

Perfusion with 200 μmol APB markedly increased the d‐wave amplitude at all stimulus intensities except for the threshold ones in both dark and light adapted eyes. The position of the V/log I curve was shifted slightly to the left along the intensity axis in dark adapted eyes, but was not changed in light adapted eyes. Thus the adaptational mechanism responsible for changes in the decremental sensitivity with increased background illumination was not altered by APB.

The effect of APB was studied also in chromatically adapted eyes, in which the responses were predominantly mediated by one photoreceptor type. The results showed that the potentiating effect of APB on d‐wave did not depend on photoreceptor input.
Effect ofin vivocorticosterone and acute food deprivation on rat resident peritoneal cell chemiluminescence after activation ex vivo
Authors: WIIK P. , SKREDE K. K. , KNARDAHL S. , HAUGEN A.‐H. , ÆRØ C. E. , OPSTAD P. K. , BØYUM A.
Published: December 2008

Adrenoglucocorticoid regulation of rat peritoneal monocyte/macrophage function was studied by exposing rats to corticosterone (CS) in the drinking water, and to fast (48 h). Production of reactive oxygen metabolites was measured by luminol amplified chemiluminescence (CL) in preparations of peritoneal cells activated by serum treated zymosan (STZ). Administration of CS which led to an increase in plasma CS from 31 (controls) to 46 ng mL_1, reduced CL (per cell) by 31%. Fast, which did not change plasma CS or ACTH, also had an inhibitory effect on CL (– 25%), while the combination of CS administration and fast strongly inhibited the CL (– 89%), indicating that plasma CS and fast reduced CL in a synergistic way. Similar effects on cell number were observed: CS‐administration, fast and the combination reduced macrophage numbers (– 13, –19.7 and –55%), while no significant effect was observed on the number of monocytes. The effect of adrenalectomy (adx) was studied in another series of experiments; adx induced no significant change in peritoneal leucocyte number or composition, while cells from adx animals had significantly higher chemiluminescence reaction than cells from sham operated animals. CS substitution in adx animals reduced CL by 30% while sham operated animals had 49% lower CL in adx. The data from adx animals also suggest that endogenous levels of CS are inhibitory for CL, but the results are not conclusive for the effect of very low doses of CS since other mechanisms than elimination of CS could prime the chemiluminescence reaction after adx. In conclusion, a moderate elevation of CS after systemic administrationin vivoreduced the total number of mononuclear phagocytes in rat peritoneum, reduced the relative number of macrophages compared with monocytes, and suppressed the function of monocytes/macrophages by reducing the production of reactive oxygen molecules in activated cells. Furthermore, the effect of corticosterone was also dependent on the physiological situation, since the effects of fast and corticosterone were synergistic.
Rat skeletal muscle metabolism in experimental heart failure: effects of physical training
Authors: BRUNOTTE F. , THOMPSON C. H. , ADAMOPOULOS S. , COATS A. , UNITT J. , LINDSAY D. , KAKLAMANIS L. , RADDA G. K. , RAJAGOPALAN B.
Published: December 2008

Skeletal muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on muscle metabolism after myocardial infarction was studied in a rat model. 31P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non‐training. Spectra were collected from the calf muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the muscles of the contralateral non stimulated leg. Post‐mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non‐trained severe heart failure group compared with the other groups. Phosphocreatine recovery half‐time was significantly longer in the non‐trained group with severe heart failure and correlated with the citrate synthase activity in the muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non‐trained severe heart failure animals. This normalization of muscle metabolism was achieved by training without any change in calf muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of skeletal muscle metabolism, implicating decreased physical activity in the aetiology of these changes.
Vasostatins, N‐terminal products of chromogranin A, are released from the stimulated calf spleen in vitro
Authors: LIANG F. , DILLEN L. , ZHANG X. Y. , COEN E. P. , HOGUE‐ANGELETTI R. , CLAEYS M. , De POTTER W. P.
Published: December 2008

Vasostatins are the N‐terminal chromogranin A peptides 7 ˜ 22 kDa. They have been shown to be present in several endocrine tissues and exhibit vasoinhibitory activity in vitro. In a first series of experiments, we investigated the presence and subcellular localization of vasostatins in the bovine splenic nerve. Experimental results, obtained using gradient centrifugation, showed that noradrenaline was enriched 25‐fold in the large dense core vesicle fraction, compared with the original homogenate. In the latter fraction, the 7 and 18 kDa peptides were observed following immunodetection with antiserum to chromogranin A1, 4o and laser densitometric scanning revealed these two fragments as the major N‐terminal fragments. Subsequently, we examined the release of the 7 and 18 kDa peptides from perfused calf spleen during veratridine (20 μM) or 1,1‐dimethyl‐4‐phenylpiperazinium iodide (20 μM) stimulation. In the prestimulatio samples, we were not able to detect these peptides, however, following stimulation, the 7 and 18 kDa chromogranin A fragments became apparent. The vasostatin‐immunoreactivity, in both bovine chromaffin granule lysate and calf spleen perfusate, elutes at the same retention time on reversed‐phase high performance liquid chromatography. The present study demonstrated that vasostatins are present in the large dense core vesicles of sympathetic axons and are released from the nerve terminals in response to stimulation. The release of vasostatins from sympathetic nerves in the spleen suggest an in vivo function for N‐terminal chromogranin A products of neuronal origin.
Central blood volume influences sympathetic sudomotor nerve traffic in warm humans
Authors: DODT C. , GUNNARSSON T. , ELAM M. , KARLSSON T. , WALLIN B. G.
Published: December 2008

The objective of this study was to test whether changes in central blood volume can induce reflex effects on sweating. Multi‐unit skin sympathetic nerve activity (SSA) was recorded from the posterior cutaneous nerve of the forearm or radial nerve branches in 11 healthy volunteers. Skin electrical resistance and skin blood flow were recorded in the area innervated by the impaled nerve fascicle. Sudomotor nerve traffic and sweating was induced by whole body heating. Lower body negative pressure (LBNP) and tilting (3d̀ head up) was used for blood volume displacement from the chest to the lower body. Low levels of LBNP (5 and 10 mmHg) had no effect on blood pressure, heart rate or skin blood flow but induced a prompt inhibition of SSA and a reduced number of transient skin resistance changes (n= 9), both rapidly returning to control levels after cessation of LBNP. Quantitatively, the effect was similar at both levels of LBNP. Head up tilting also reduced SSA (n= 3, tilt manoeuvres). A capacity for mental stress‐induced SSA increase remained during LBNP. Spontaneous flucturations in blood pressure did not affect SSA, arguing against arterial (high‐pressure) baroreceptors modulating SSA. Consequently, the present results indicate that unloading of cardiopulmonary (low‐pressure) volume receptors reduces sympathetic sudomotor nerve traffic and sweating in warm subjects. It is suggested that the reflex contributes to counteracting hypovolaemia.
The insulin secretory response to intravenous glucose in the rat is independent of NO formation
Authors: JUN T. , SAKINIS A. , WENNMALM Å.
Published: December 2008

In isolated pancreative β cells from rats the insulin secretory response to glucose is amplified by L‐arginine. Since this effect is inhibited by NO synthesis inhibitors, and since L‐arginine is precursor or NO, the observation indicates a role for NO in insulin secretion from β cells. We recently reported that i. v. L‐arginine elicited insulin secretion in anaesthetized rats by a mechanism that was partly NO dependent. The aim of the present study was to assess if the insulin secretory response to an intravenous infusion of glucose also requires an intact NO formation. Anaesthetized rats were given D‐glucose (100 mg kg‐1min‐1i. v. for 30 min). Plasma insulin (PI), blood glucose (BG) levels and mean arterial blood pressure (MAP) were assessed from before and until 15 min after the end of the infusion. One group of rats were untreated and served as controls. The two other groups were pretreated with either of the NO synthase inhibitorsNw‐nitro‐L‐arginine methyl ester (l‐NAME, 50 mg kg‐1i. v.), orNG‐monomethyl‐L‐arginine (l‐NMMA, 100 mg kg‐1i. v.). In controls infusion of glucose elevated PI by up to 25pL3 UL‐1, and BG by up to 27pL1 mmol L‐1. Pretreatment withl‐NAME elevated MAP from 74pL6 to 132pL4 mmHg, indicating that NO synthase was inhibited. Infusion of glucose in rats pretreated withl‐NAME increased PI by up to 28pL2 UL‐1, and elevated BG by up to 30pL1 mmol L‐1. Pretreatment withl‐NMMA elevated MAP from 80pL5 to 132pL1 mmHg. Infusion of glucose in these rats increased PI by up to 23pL3 UL‐1, and elevated BG by up to 29pL2 mmol L‐1. The PI and BG responses to glucose infusion were not significantly affected by either of the NO synthase inhibitors studied. We conclude that the insulin secretory response to i. v. glucose infusion in the rat does not require an intact formation of NO.
Fluid flow across the jejunal epithelia in vivo elicited by d‐c current: effects of mesenteric nerve stimulation
Authors: HEMLIN M.
Published: December 2008

The aim of this study was twofold: (1) to investigate the effect of eletrical gradients on fluid transport across the rat jejunal mucosa in vivo; and (2) to evaluate the effect of mesenteric nerve stimulation (MNS) on current‐induced fluid flow. Segments of rat jejunum were mounted with intact blood circulation in an in vivo chamber, allowing parallel registration of net fluid transport rate (NFT) and electrical properties of the tissue. Directed currents (d‐c) of varying densities were passed across the jejunal wall in both directions and teh current‐induced fluid flows were measured. D‐c current elicited fluid flows across the jejunal mucosa towards the cathode in both directions in a ‘dose‐dependent’ manner. The effect was markedly greater when the anode was placed on the serosal side (s → m current) than when it was placed on the mucosal side (m‐s current). MNS abolished m → s current induced flow whereas the effect of s → m curent was not significantly changed. It was concluded that: (1) true electro‐osmosis probably accounts for the major portion of current‐induced fluid flow in this model; (2) current induced fluid flow is rectified in opposite directions in vivo and in vitro; and (3) MNS inhibits current‐induced fluid flow m → s, possibly via a sympathetic effect on epithelial permeability.
Effect of furosemide on local and zonal glomerular filtration rate in the rat kidney
Authors: TENSTAD O. , WILLIAMSON H. E.
Published: December 2008

Furosemide has been reported to produce disproportional changes in blood flow in cortical zones and to inhibit tubuloglomerular feedback (TGF), suggesting that furosemide might alter the intracortical distribution of glomerular filtrate. We have tested this hypothesis by a new method for measuring local and total glomerular filtration rate (GFR) based on proximal tubular accumulation of the basic polypeptide aprotinin (mol wt 6513). Local GFR was calculated in tissue samples dissected from outer cortex (OC), inner cortex (IC) and the corticomedullary border zone (CM) from the plasma clearances of two aprotinin tracers injected i. v. before and after a 3 min i. v. infusion of 25 mg kg‐1 furosemide. The mean of five samples from each region was used to determine zonal GFR. Isotonic saline was infused at a rate corresponding to urine flow. Furosemide reduced whole kidney GFR from 1.17 to 1.00 mL min‐1 and gave a similar reduction of renal artery blood flow. Urine flow increased from 0.6 to 17% of GFR. Haematocrit (˜ 0.48) and plasma protein concentration (˜ 55 mg mL‐1) were maintained while the arterial blood pressure tended to decline (118pL5 mmHg to 108pL6 mmHg, P < 0.05). GFR in OC, IC and CM (1.58, 1.18, 0.42 mL min‐1 g‐1) fell to 87, 88 and 88% of control after furosemide infusion respectively. The furosemide/control ratio for each sample showed a coefficient of variation of about 3%. We conclude that furosemide produced a modest GFR reduction that was uniform throughout the renal cortex. The homogenous GFR response suggests a similar TGF constriction tone in preglomerular vessels of deep and superficial nephrons.
The intestinal tract and the pathophysiology of arterial hypertension: an experimental study on Dahl rats
Authors: MU J. Y. , HANSSON G.C. , LUNDGREN O.
Published: December 2008

Salt depleted rabbits and humans excrete an oral sodium load more quickly via the kidneys than an intravenous one. This has been ascribed to the presence of a sodium sensor in the gastrointestinal tract which in some way can influence renal function. The purpose of this study was to investigate this response in the Dahl rats. Renal and faecal sodium excretion was followed in the two strains of rats (normotensive, saltresistant (SR/Jr) and hypertensive, saltsensitive (SS/Jr) rats). After 4 days on a low salt diet they were given NaCl(l.5 mmol kg‐1 body wt) either by gavage or intravenously. SR/Jr rats showed an increased renal sodium excretion both after oral and intravenous sodium repletion. The excretion was 2–3 times greater after the oral than after the intravenous administration. The SS/Jr rats augmented their renal sodium excretion only after the oral load, although the sodium excretion was significantly less than in SR/Jr rats. In fact, during the first 8 h after giving sodium orally the renal excretion of sodium was on an average eight times larger in the SR/Jr than in the SS/Jr rats. Renal excretion of sodium was similar in the two strains after intravenous administration. We conclude that the hypertensive SS/Jr rats have great difficulties in excreting an oral sodium load, a phenomenon that may be of importance in the pathophysiology of arterial hypertension in this strain of rats.
Comparison of the effects of 2‐deoxyglucose and immobilization on secretion and synthesis rate of catecholamines in the adrenal gland: a microdialysis study in conscious rats
Authors: KUZMIN A. I. , POGORELOV V. M. , ZARETSKY D. V. , MEDVEDEV O. S. , CHAZOV E. I.
Published: December 2008

Using microdialysis, extracellular 3,4‐dihydroxyphenylalanine (DOPA), noradrenaline (NA) and adrenaline (AD) concentrations in the adrenal gland were monitored in conscious rats during and after 60 min of immobilization (IMM) as well as after injection of 500 mg kg‐12‐deoxyglucose (2‐DG). IMM produced a rapid and transient increase in secretion of AD (20‐fold), NA (13‐fold) and DOPA (3.6‐fold). This was accompanied by an increase in blood pressure (+ 18 mmHg) and heart rate (‐ 146 b. p.m.). Repeated exposure to IMM (daily 60 min, for 5 days) had no influence on either catecholamine secretion of haemodynamic profiles, indicating the lack of habituation to stressful conditions. Unlike IMM, the stress of 2‐DG‐induced centralneuroglucopenia stimulated the release of AD without affecting NA secretion. AD levels peaked (5.1‐fold increase) 4&60 min after 2‐DG injection and then slowly declined. 2‐DG induced no changes in blood pressure but reduced the heart rate (‐48 b. p.m.). In separate experiments, steady‐state dialysate DOPA levels, reached during continuous infusion of decarboxylase inhibitor NSD 1015 into adrenal gland tissue through the dialysis probe, served as an index of adrenomedullary tyrosine hydroxylase (TH) activity. IMM evoked a marked increase in TH activity (DOPA formation increased 2.7‐fold), which remained elevated 60 min after the cessation of stress when AD and NA secretion had already fallen to baseline. After 2‐DG, despite significant hormonal response, adrenal TH activity was unchanged. These results give clear evidence that IMM and 2‐DG‐induced neuroglucopenia may be considered as two different types of stressful stimuli.
Sympathetic vascular control of the laryngeo‐tracheal, bronchial and pulmonary cicrualtionin the pig: evidence for non‐adrenergic mechanisms involving neuropeptide Y
Authors: FRANCO‐CERECEDA A. , MATRAN R. , ALVING K. , LUNDBERG J. M.
Published: December 2008

Neuropeptide Y (NPY) and noradrenaline (NA) are co‐stored in sympathetic perivascular nerves of the airway mucosa and lung. The superior laryngeal, bronchial and pulmonary vascular responses were therefore studied in anaesthetized pigs after systemic injections of NPY and NA and after stimulation (2 or 10 Hz, 15 V, 5 ms) of the cranial and caudal portions of the cervical sympathetic trunk or the stellate ganglia. NPY and NA increased vascular resistance, suggesting vasoconstriction in all three vascular beds. Stimulation of the cervical sympathetic trunk in the cranial direction caused clear‐cut vasoconstriction and a decrease in the superficial blood flow in the laryngeal and tracheal circulation supplied by the superior laryngeal artery. This vascular response may be related to release of NA at 2 Hz and possibly also NPY at 10 Hz, since a remaining vasoconstrictor response at 10 Hz was present in reserpinized preganglionically transected pigs when tissue content of NA but not NPY was depleted. The decrease in superficial blood flow in the tracheal mucosa on sympathetic stimulation was absent after reserpine, however. Stimulation of the cervical sympathetic trunk in caudal direction provoked vasoconstriction in the bronchial and pulmonary vascular beds in control pigs. The basal tone of these two vascular beds was not influenced on electrical stimulation after reserpine pretreatment, however, suggesting involvement of NA and possibly also NPY, which were both depleted by reserpine. Electrical stimulation of the stellate ganglia also evoked reserpine‐sensitive vasoconstriction in both the bronchial and pulmonary vascular beds. The left stellate ganglion dominated the vasomotor response in the bronchial circulation, whereas the right side mainly influenced the pulmonary circulation and the heart.
Glucagon secretory response to hypoglycaemia, adrenaline and carbachol in streptozotocindiabetic rats
Authors: AHRÉN B. , STERN J. S. , GINGERICH R. L. , CURRY D. L. , HAVEL P. J.
Published: December 2008

Glucagon response to insulin‐induced hypoglycaemia is impaired in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg‐1min‐1for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 μ kg‐1) in chloral hydrate‐anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg‐1subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L‐1. As expected, the plasma glucagon response was reduced by ∼ 45% in streptozotocindiabetic rats compared with controls (P= 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 ± 92 pg mL‐1in controls (P= 0.009) and by 570 ± 137 pg mL‐1in the diabetic rats (P= 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P= 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 ± 208 pg mL‐1(P< 0.001) in controls but only by 555 ± 242 pg mL‐1in the diabetic rats (P= 0.049). Thus, the plasma glucagon response to carbachol was impaired by ∼ 58% in the diabetic rats (P= 0.028). We conclude that carbachol‐stimulated glucagon secretion is impaired concomitantly with the impaired glucagon response to hypoglycaemia in streptozotocin‐diabetic rats, whereas adrenaline‐induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulininduced hypoglycaemia in diabetes.
Attenuation of low pH‐, but not capsaicin‐ or PGI2‐ evoked CGRP ‐ release by endothelium removal using saponin
Authors: KÄLLNER G. , FRANCO‐CERECEDA A.
Published: December 2008

The aim of the present study was to evaluate the role of the endothelium in low pH‐, capsaicin‐, and prostacyclin (PGI2,)‐evoked release of calcitonin gene‐related peptide (CGRP)‐like immunoreactivity (‐LI) from C‐fibre afferents in the isolated, perfused guinea‐pig heart. CGRP‐LI release, and formation of the stable PGI2‐metabolite 6‐keto‐PGF1α, in response to moderate acidosis (pH 7, 6, but not 5) were significantly reduced after removal of the endothelium using saponin (50 μg mL‐1) perfusion. In contrast, the release of CGRP‐LI evoked by capsaicin (10‐7 M) or PGI2, (10‐5 M) remained unchanged after removal of the endothelium. Saponin treatment did not influence the vasodilator action of CGRP, whereas the vasodilation evoked by substance P (SP) was abolished. It is concluded that CGRP release evoked by low pH, but not that evoked by capsaicin or exogenous PGI2, is partly endothelium dependent. Our data suggest that endothelially produced PGI2, is involved in low pH‐evoked release of CGRP from capsaicin sensitive nerves in the heart.
The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic ‘tone’
Authors: HEDMAN A. E. , HARTIKAINEN J. E. K. , TAHVANAINEN K. U. O. , HAKUMÄKI M. O. K.
Published: December 2008

This study was designed to evaluate the effect of modulating cardiac parasympathetic input on the high frequency component of heart rate variability. We stimulated the right vagus nerve with three different stimulation patterns in anaesthetized, vagotomized and spinal anaesthetized dogs. We kept the mean stimulation frequency constant; controlled the amplitude of modulation with programmed stimulation patterns, and analysed the resulting heart rate variability by power spectral analysis. Constant frequency vagal stimulation increased the cardiac interval, but did not change heart rate variability markedly. There was a slight increase, from 11 pL 2 to 27 pL 11 ms2, in the high frequency component. However, when the instantaneous stimulation frequency oscillated between 4 and 17 Hz during 5 s period, we could produce a marked heart rate variation, with 91 pL 9% of the variation corresponding to the frequency of the modulation (0.20 Hz). The high frequency component was 12932 pL 7701 ms2. With an increased magnitude of modulation, i.e. the difference between minimum and maximum instantaneous frequency, the high frequency component increased to 32711 pL 17943 ms2. Thus, the high frequency component of heart rate variability reflects the magnitude of fluctuation in the cardiac parasympathetic input rather than parasympathetic ‘tone’.
Theophylline increases coronary vascular tone in humans: evidence for a role of endogenous adenosine in flow regulation
Authors: EDLUND A. , SOLLEVI A.
Published: December 2008

To elucidate the role of adenosine in coronary vasoregulation, we studied the effects of adenosine antagonism (by theophylline) on coronary blood flow at different levels of adenosine formation (stimulated by hypoxia and exercise). Six healthy subjects were studied. Coronary sinus (CS) blood flow (thermodilution) and cardiac oxygen extraction {(A‐CS)O2D} were determined while breathing room air at rest, and 12% oxygen, both at rest and during light exercise, on two occasions. One of the experiments was performed during infusion of theophylline. The basal CS flow was 118 (67–168) mL min‐1(mean and 95% confidence interval), and the (A‐CS)O2D was 125 (111–142) mL L‐1.Inhalation of 12% 02decreased the arterial haemoglobin oxygen saturation to 83 (80–86)% at rest and to 77 (73–81)% during exercise. CS flow increased to 167 (93–214) and 261 (179–343) mL min‐1, respectively, and (A‐CS)O2D decreased to 102 (85–119) and 94 (77–111) mL L‐l, respectively. Theophylline, at a dose lacking effects on myocardial work, markedly attenuated the coronary flow response to exogenous adenosine, and decreased CS flow to 89 (58–119), 120 (79–161) and 190 (162–218) mL min‐1at normoxic rest, hypoxic rest and hypoxic exercise, respectively. The overall decrease amounted to 23% (P < 0.05). The calculated coronary vascular conductance also decreased by 23% (P < 0.05) and (A‐CS)O2D increased by 15% (P < 0.001). In conclusion, the data support the hypothesis that endogenous adenosine is involved in regulation of human coronary tone.
Ca selectivity of the transduction channels in the hair cells of the frog sacculus
Authors: GENSEN F. JØ , KROESE A. B. A.
Published: December 2008

The extracellular receptor currents evoked by step displacements of the otolithic membrane of the isolated saccular macula ofRana esculentawere recorded under transepthelial voltage clamp conditions. With the aim to depolarize the hair cells and increase the fractional resistance of the apical membrances, the basal side of the preparation was bathed in saline with an increased K+concentration (62 mm). This caused a shift in the non‐linear receptor current‐voltage relation along the voltage axis of ‐51 mVpL10 mV; (mean pL SD; n= 32) and a reduction in the transepithelial resistance of 10%. Under these conditions the electrical properties of the macula are assumed to be controlled by the apical membranes. The effects of different concentrations of Ca2+in the apical solution on the receptor current‐voltage relation were examined.

Change of the apical Ca2+concentration (range 3 mM to 70 μM) varied the transepithelial voltage at which the receptor current was zero (Vrev). Fitting a modified constant field equation to the relation between the apical Ca2+concentration and the change in Vrevgave an estimate of Pca/Pkof the transduction channels of 212. Furthermore, a high relative permeability of the transduction channels for other divalent cations (Ba2+, Sr2+) was measured, whereas Mn2+inhibited the receptor current. The receptor current was inhibited by amiloride (IC503.2 μM) and nifedipine (IC501.9 μM pL0.6 μM).

Reduction of the apical Ca2+concentration to 90μM in standard apical solution reduced the size of the receptor current to 67% pL 30% (n=17) compared to control but did not affect the shape of the receptor current ‐voltage relation. Subsequent substitution of K+by Na+caused a further reduction of the receptor current to 32% pL29% (n=9), changed the receptor current‐voltage relation into a linear relation and diminished the adaptation of the receptor current.

These results indicate that the mechano‐electrical transduction channels of the frog saccular hair cells are highly selective to Ca2+and that the conductance of the channels may be influenced by the apical monovalent cation species.
Influence of forebrain lesions and isoflurane anaesthesia, respectively, on responses to the intracarotid infusion of angiotensin II in sheep
Authors: ERIKSSON S. , ANDERSSON B. , RUNDGREN M.
Published: December 2008

In conscious sheep, lesions involving the anterior wall of the third cerebral ventricle extinguished the dipsogenic and cortisol releasing effects of 10 min intracarotid (i. c.) infusions of angiotensin II (Ang II) (20 pmol kg‐1 min‐1). The sustained hypertension obtained in response to i. c. Ang II in the intact animal was not significantly changed by the forebrain lesions. Pronounced, but short‐lasting tachycardia immediately developed in response to i. c. Ang II in control animals. After a 1 min return to initial values the heart rate (HR) rose to about 20 beats min‐1 above pre‐infusion level during the remaining infusion period. After a brief post‐infusion fall, HR retook that level. It then gradually declined but did not return to initial level until about 25 min later. During isoflurane anaesthesia in the latter animals carotid blood pressure (cBP) was reduced by ˜ 30% while the HR was more than doubled. The cBP rise in response to i. c. Ang II infusion was < 50% of that seen in awake animals and the pressure returned to initial level within ˜ 5 min after the end of the infusion. The infusion did not influence the HR. This study provides support for the idea that blood borne Ang II, bound at cerebral sites posterior to the hypothalamic reion, continues to have cardiovascular effects for ˜ 20 min after the concentration in the blood has returned to pre‐infusion level.
Fluorescence Investigation of the Binding of Model PDT Drugs to Nonionic and Zwitterionic Surfactants
Authors: Patel Sunita , Datta Anindya
Published: December 2008

The binding of two model photodynamic therapy drugs, chlorin p6 and purpurin 18, with surfactants has been studied using steady‐state and time‐resolved fluorescence techniques. The surfactants used are amphiphilic nonionic surfactant (Tween 80 and Tween 40) and zwitterionic surfactant (HAPS). These have applications in drug delivery. The studies have been performed at pH 7 and 5 for chlorin p6 and at pH 7 for purpurin 18. The binding constants have been estimated from the change in fluorescence parameters and have been compared with those for Cremophor EL and human serum albumin. Chlorin p6 is found to bind to the surfactants to a greater extent at pH 5 than at pH 7. The same ionic species of chlorin p6 is found to exist at the maximum concentrations of the surfactants.
Photoprocesses of Xanthene Dyes Bound to Lysozyme or Serum Albumin
Authors: Zhang Yazhou , Görner Helmut
Published: December 2008

The ground and excited state processes of eosin, erythrosin and rose bengal in aqueous solution were studied in the presence of lysozyme or bovine serum albumin (BSA). Noncovalent protein‐dye binding was analyzed by circular dichroism (CD), fluorescence and UV–Vis absorption spectroscopy. The effects of protein concentrations and pH were studied. Fluorescence quenching of the dye takes place due to binding to lysozyme and fluorescence enhancement due to low loading to BSA. The effects of proteins on the xanthene triplet state and its precursor were observed by time‐resolved 530 nm photolysis. The triplet lifetime is quenched by lysozyme and prolonged by loading to BSA. Light‐induced damages on both the dyes and proteins were observed under exclusion of oxygen. Photo‐oxidation is efficient for lysozyme and lower for BSA. The CD signal of the eosin/BSA system is maximum at pH 4, where the photo‐oxidation is minor.
PERSPECTIVE ARTICLE: Why do adaptive immune responses cross‐react?
Authors: Fairlie‐Clarke Karen J. , Shuker David M. , Graham Andrea L.
Published: December 2008

Antigen specificity of adaptive immune responses is often in the host’s best interests, but with important and as yet unpredictable exceptions. For example, antibodies that bind to multiple flaviviral or malarial species can provide hosts with simultaneous protection against many parasite genotypes. Vaccinology often aims to harness such imprecision, because cross‐reactive antibodies might provide broad‐spectrum protection in the face of antigenic variation by parasites. However, the causes of cross‐reactivity among immune responses are not always known, and here, we explore potential proximate and evolutionary explanations for cross‐reactivity. We particularly consider whether cross‐reactivity is the result of constraints on the ability of the immune system to process information about the world of antigens, or whether an intermediate level of cross‐reactivity may instead represent an evolutionary optimum. We conclude with a series of open questions for future interdisciplinary research, including the suggestion that the evolutionary ecology of information processing might benefit from close examination of immunological data.
The Effect of Fiduciary Standards on Institutions' Preference for Dividend‐Paying Stocks
Authors: Hankins Kristine Watson , Flannery Mark J. , Nimalendran M.
Published: December 2008

Many researchers apparently believe that some institutional investors prefer dividend‐paying stocks because they are subject to the “prudent man” (PM) standard of fiduciary responsibility, under which dividend payments provide prima facie evidence that an investment is prudent. Although this was once accurate for many institutions, during the 1990s most states replaced the PM standard with the less‐stringent “prudent investor” (PI) rule, which evaluates the appropriateness of each investment in a portfolio context. Controlling for the general decline in dividend‐paying stocks, we find that institutions reduced their holdings of dividend‐paying stocks by 2% to 3% as the PI standard spread during the 1990s. Studies of asset pricing and corporate governance should no longer consider dividend payments when evaluating the actions of institutional investors.
Mean Value Modeling and Analysis of HCCI Diesel Engines With External Mixture Formation
Authors: Canova Marcello , Midlam-Mohler Shawn , Guezennec Yann , Rizzoni Giorgio
Published: December 2008

Homogeneous charge compression ignition (HCCI) is a promising concept for internal combustion engines that can considerably decrease NOx and soot emissions in part-load operations without penalizing fuel consumption. The HCCI combustion can be implemented in direct injection diesel engines without major modifications by introducing a specialized fuel injector in the intake port. This decouples the homogeneous mixture formation from the traditional in-cylinder injection, thus providing two fueling systems that can be used to optimize exhaust emissions and fuel consumption over the engine operating range. However, understanding and controlling the complex mechanisms and interactions driving the HCCI combustion process is still a difficult task. For this reason, it is essential to identify the most important control parameters and understand their influence on the auto-ignition process. The current work analyzes HCCI combustion with external mixture formation through experimental investigation and the definition of a control-oriented model. An extensive testing activity was performed on a passenger car diesel engine equipped with an external fuel atomizer to operate in HCCI mode. This provided an understanding of the process as well as experimental data to identify a mean value model of the system and its parameters. The model includes a thermodynamic combustion calculation that estimates the heat release, cylinder pressure, and the relevant variables for combustion control. The tool developed was then validated and used for analyzing the system behavior in steady state conditions. Finally, a description of the HCCI system behavior in transient operations is presented.
Quantification of Uncertainty in Reserve Estimation From Decline Curve Analysis of Production Data for Unconventional Reservoirs
Authors: Cheng Yueming , Lee W. John , McVay Duane A.
Published: December 2008

Decline curve analysis is the most commonly used technique to estimate reserves from historical production data for the evaluation of unconventional resources. Quantifying the uncertainty of reserve estimates is an important issue in decline curve analysis, particularly for unconventional resources since forecasting future performance is particularly difficult in the analysis of unconventional oil or gas wells. Probabilistic approaches are sometimes used to provide a distribution of reserve estimates with three confidence levels (P10, P50, and P90) and a corresponding 80% confidence interval to quantify uncertainties. Our investigation indicates that uncertainty is commonly underestimated in practice when using traditional statistical analyses. The challenge in probabilistic reserve estimation is not only how to appropriately characterize probabilistic properties of complex production data sets, but also how to determine and then improve the reliability of the uncertainty quantifications. In this paper, we present an advanced technique for the probabilistic quantification of reserve estimates using decline curve analysis. We examine the reliability of the uncertainty quantification of reserve estimates by analyzing actual oil and gas wells that have produced to near-abandonment conditions, and also show how uncertainty in reserve estimates changes with time as more data become available. We demonstrate that our method provides a more reliable probabilistic reserve estimation than other methods proposed in the literature. These results have important impacts on economic risk analysis and on reservoir management.
Identification of Time-Varying Time Constants of Thermocouple Sensors and Its Application to Temperature Measurement
Authors: Kar Kenneth , Swain Akshya K. , Raine Robert
Published: December 2008

The present study addresses the problem of estimating time-varying time constants associated with thermocouple sensors by a set of basis functions. By expanding each time-varying time constant onto a finite set of basis sequences, the time-varying identification problem reduces to a parameter estimation problem of a time-invariant system. The proposed algorithm, to be called as orthogonal least-squares with basis function expansion algorithm, combines the orthogonal least-squares algorithm with an error reduction ratio test to include significant basis functions into the model, which results in a parsimonious model structure. The performance of the method was compared with a linear Kalman filter. Simulations on engine data have demonstrated that the proposed method performs satisfactorily and is better than the Kalman filter. The new technique has been applied in a Stirling cycle compressor. The sinusoidal variations in time constant are tracked properly using the new technique, but the linear Kalman filter fails to do so. Both model validation and thermodynamic laws confirm that the new technique gives unbiased estimates and that the assumed thermocouple model is adequate.
Robust and Simplified Design of Slip Control System for Torque Converter Lock-Up Clutch
Authors: Hibino R. , Osawa M. , Kono K. , Yoshizawa K.
Published: December 2008

A torque converter lock-up clutch slip control system, which is designed to improve fuel economy, must be able to precisely regulate slip speed. Also the system must have a high level of robustness for coping with changes in the operating conditions and any deterioration in the automatic transmission fluid and the clutch. Moreover, to reduce the design time, the design process must be as simple as possible. In this paper, we first propose a loop shaping that aims to optimize complementary sensitivity function of the control system, while satisfying the abovementioned requirements of performance and robustness. Next, a method for simplifying the design process is proposed, that is, a model and a controller are expressed by interpolation. A controller set, which has a relationship of duality to the interpolation parameters of the model, is created in advance so that the construction of a new control system can be realized by identifying the characteristic parameters only. From application to the actual design process for a vehicle, we verified that the design time was reduced to less than 1∕3 of that required for the conventional method. This new method has already been adopted for the design and fitting of new products.