Variations in arterioles in spontaneously hypertensive rats

Summary In the present study, the diameters of afferent and efferent arterioles of kidneys from spontaneously hypertensive rats (SHR) were evaluated and compared with those from Wistar Kyoto rats (WKY) using a vascular cast model. At 4 weeks of age, the blood pressure was slightly higher in SHR than in WKY (124±1 vs 116±7 mmHg, ns). The diameters of afferent arterioles in SHR were smaller than those in WKY (10.3±0.6 vs 12.3±0.7 µm,P<0.001), whereas the diameters of efferent arterioles were comparable in the two strains. At 20 weeks of age, the blood pressure was markedly elevated in SHR than in WKY (192±5 vs 140±4 mmHg,P<0.001). The diameters of afferent arterioles in SHR at this age were much smaller than those in WKY (14.3±0.5 vs 17.1±0.6 µm,P<0.01). The diameters of efferent arterioles in SHR were, however, larger than those in WKY (15.4±l.2 vs 12.9±0.4 µm,P< 0.05). The net effect of these changes in arteriolar size helps to maintain normal intraglomerular pressure and to protect glomeruli from damage due to hypertension.     

Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8–14.7 mm Hg) and stop-flow pressures (40.0–42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY. Maximum TGF pressure response was 28.6% greater in SHR than in the normotensive rats (13.3 vs. 9.5 mm Hg;p<0.025). The sensitivity, as estimated from the slope of the feedback curve at the Tp [f(Tp)] was 87% greater in SHR than in WKY. There was no significant difference between these parameters in WKY and SPRD. The TGF pressure response was biphasic in the 3 groups of halothane anaesthetized rats with a steady state level reached in about 2 min after the change in late proximal microperfusion rate. In inactin anaesthetized rats the sensitivity was 41% lower than in the halothane anaesthetized control group of SPRD, the feedback response was lower, and the feedback curve was displaced to the right with the Tp at 15.9 nl/min, significantly higher than in the control group (p<0.001). Although the steady state level also was reached within 2 min, the clearly biphasic pattern of the pressure response was less consistent.     

Differential expression of α-enolase in the normal and pathological cardiac growth

Objectives

It was found that α-enolase was dramatically up-regulated in the hypertrophic hearts of SHR in our previous study. The purposes of this study were to examine the expression pattern of α-enolase in pre- and postnatal myocardium of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and to explore the relationship between the overexpression of α-enolase and left ventricular hypertrophy.

Methods

HE staining was used for the measurement of cardiac hypertrophy. Immunohistochemical technique was used to evaluate the location of α-enolase. The expressions of α-enolase in the left cardiac ventricles at different development times were examined by Real-time RT-PCR and Western blot.

Results

Cardiac hypertrophy was found in SHR rats at 4 weeks of age and remained up to 24 weeks of age. The signals of α-enolase protein were strong and existed extensively in hypertrophic myocardium in SHR, while in the normal myocardium of WKY, the signals were scarcely found and weak. The levels of α-enolase mRNA and protein in SHR and WKY hearts during fetal stage and newborn stage were similar, while from 4 weeks of age to 24 weeks of age, accompanied by the cardiac hypertrophy, the levels of α-enolase mRNA and protein in left ventricle of SHR were significantly higher than that in WKY.

Conclusions

The expressions of α-enolase in the left ventricle of the rats during normal and pathological cardiac development were different. This phenomenon provides the potential clues to understanding pathophysiological mechanisms in cardiac hypertrophy of SHR.     

Effects of diadenosine polyphosphates,ATP and angiotensin II on cytosolic Ca2+ activity and contraction of rat mesangial cells

Diadenosine polyphosphates (Ap _n A) are known to influence cellular Ca²⁺ activity ([Ca²⁺]_i) in several cells. Their vasoactive potency has been described in various systems including the kidney. We examined the effects of diadenosine polyphosphates, adenosine 5-triphosphate (ATP) and angiotensin II (Ang II) on cytosolic Ca²⁺ activity of mesangial cells (MC) in culture obtained from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. [Ca²⁺]_i was measured as a fluorescence ratio F ₃₄₀/F ₃₈₀ with the fura-2 technique using three excitation wavelengths (340 nm, 360 nm and 380 nm) and a photon counting tube. Resting [Ca²⁺]_i was not significantly different in MC from WKY and SHR rats and was measured as 132±9 nmol/l (n=65) and 114±12 nmol/l (n=36), respectively. Diadenosine polyphosphates (Ap₃A–Ap₆A) increased [Ca²⁺]_i transiently with an initial peak and a secondary plateau phase comparable to the effects of ATP or Ang II. Increases in [Ca²⁺]_i induced by all these agonists were not significantly different between MC of WKY and SHR rats. ATP, Ap₃A, Ap₄A, Ap₅A, Ap₆A (each 5 mol/l) increased the fura-2 fluorescence ratio initially by 0.66±0.09 (n=33), 0.52±0.08 (n=18), 0.25±0.05 (n=16), 0.09±0.06 (n=7), 0.09±0.04 (n=11), respectively. A half-maximal initial increase in the fura-2 fluorescence ratio was reached at 22 nmol/l, 0.9 mol/l, 2.0 mol/l and 4.0 mol/l with Ang II, Ap₃A, ATP and Ap₄A, respectively. Ap₄A (100 mol/l, n=18) led to a reversible contraction of MC. Diadenosine polyphosphates increase [Ca²⁺]_i in rat MC, in a similar manner to ATP or Ang II and lead to a contraction of MC, suggesting that these nucleotides are also involved in the control of glomerular haemodynamics.     

The effect of renal perfusion pressure on renal vascular resistance in the spontaneously hypertensive rat

Renal hemodynamics and renal vascular resistance (RVR) were measured in the spontaneously hypertensive rat (SHR) and in the normotensive Wistar-Kyoto rat (WKY). In addition, the autoregulatory response and segmental RVR in the SHR were studied after aortic constriction. Mean arterial pressure (MAP) and RVR were higher in the SHR than in the WKY, but renal blood flow (RBF) and glomerular filtration rate were similar in both groups. Measurement of mean afferent arteriolar diameter (AAD) by a microsphere method showed a significantly smaller AAD in SHR (17.7±0.35 m) than in the WKY (19.5±0.20 m). This decrease in AAD could account for a 47% increase in preglomerular resistance. Aortic constriction in the SHR, sufficient to reduce renal perfusion pressure from 152 to 115 mm Hg, did not alter the AAD. Since RBF and glomerular filtration were also well maintained following aortic constriction, these autoregulatory responses suggest that vessels proximal to the afferent arteriole rather than postglomerular vasculature are primarily involved in the changes on intrarenal vascular resistance in SHR.     

The effect of alkaline pH and transmural pressure on arterial constriction and membrane potential of hypertensive cerebral arteries

These studies were undertaken to examine the effect of alkalosis to modify pressure-induced activation of isolated cerebral arteries from spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. At pH 7.4 andPCO₂ of 34 torr elevation of transmural pressure from 0–140 mm Hg resulted in myogenic activation preceeded by membrane depolarization in both SHR and WKY. The degree of developed myogenic tone in SHR was elevated above WKY. Aklalosis (pH 7.4–7.7) depolarized and activated SHR cerebral arteries to a greater extent than WKY. Furthermore, both the electrical and mechanical responses to elevation in transmural pressure were exaggerated in SHR compared to WKY at pH 7.7 (PCO₂ constant at 34 torr).Manipulation ofPCO₂ at constant pH of 7.4 had similar effects on pressure-induced myogenic tone in both SHR and WKY. Thus, cerebral arteries from both SHR and WKY depolarize and develop myogenic tone in response to increasing transmural pressure. This response is augmented in SHR, but to a much greater extent upon elevation of extracellular pH, whilePCO₂ is maintained within normal limits. The implications of these findings are discussed.D. R. Harder is an Established Investigator of the American Heart Association and a Research Career Scientist of the Veterans Administration. This study supported by NIH grants 33833 and 31871 and the Veterans Adminstration.     

The correlation of cardiac mass with arterial haemodynamics of resistive and capacitive load in rats with normotension and established hypertension

In hypertensive animals and humans, cardiac hypertrophy may occur as a consequence of an external load on the heart. Several studies have suggested that the non-pulsatile components of arterial haemodynamics, such as arterial pressure and vascular resistance, do not adequately represent the ventricular afterload and are not well correlated with the degree of cardiac hypertrophy (CH). The present study was undertaken to analyse the correlation between the degree of CH and various haemodynamic parameters in the spontaneously hypertensive rat (SHR) with established hypertension. A total of 36 SHRs (6–8 months) with a tail-cuff pressure above 190 mm Hg were used. Control data were obtained from 32 age-matched normotensive Wistar Kyoto rats (WKY). Animals were anaesthetized with pentobarbitone sodium (40 mg/kg i.p.) and artificially ventilated with a respirator. A Millar catheter with a high-fidelity pressure sensor was used to record the aortic pressure and an electromagnetic flow transducer to monitor the aortic flow. The pressure and flow signals were subjected to Fourier transformation for the analysis of the arterial impedance spectrum. The left ventricular weight-to-body weight ratio (LVW/BW) was taken as a measure of the degree of CH. The measured haemodynamic parameters in these anaesthetized, open-chest SHRs were systolic pressure (SP) (mean ± SE) 172±4 mm Hg, diastolic pressure (DP), 120±3 mm Hg, pulse pressure (PP) 52±2 mm Hg, peripheral resistance (R _p) 344,032±8,012 dyne · s · cm^–5, characteristic impedance (Z_c) 6,442±313 dyne · s · cm^–5, the impedance modulus at the first harmonic (Z1) 26,611±1,061 dyne · s · cm^–5, mean arterial compliance (C _m) 0.87 ±0.04 l/mm Hg and LVW/BW 3.092±0.026 mg/g. These parameters were significantly greater than the corresponding values in WKY, except that C _m was much decreased. In SHR, the LVW/BW was not significantly correlated with the SP, DP, R _p and steady external power. In contrast, the degree of CH was positively correlated with Z_c (r=0.66, P<0.001), Z1 (r=0.62, P<0.001) and pulsatile external work (r=0.41, P<0.05). It was also positively correlated with the backward pressure wave (r=0.42, P<0.05) and negatively correlated with C _m (r=-0.72, P<0.01). Such correlations of LVW/BW with pulsatile haemodynamics were not found in the normotensive WKY. The results indicate that the degree of cardiac hypertrophy in hypertensive rats, with a high blood pressure and increased stiffness of the arterial tree, is more closely related to pulsatile arterial haemodynamics than to the nonpulsatile components.     

Maximal cardiorespiratory responses to one- and two-legged cycling during acute and long-term exposure to 4300 meters altitude

Summary During exposure to altitudes greater than about 2200 m, maximal oxygen uptake ( ) is immediately diminished in proportion to the reduction in the partial pressure of oxygen in the inspired air. If the exposure lasts longer than a couple of days, an increase in arterial oxygen content (CaO₂), due to a hemoconcentration and an increase in arterial oxygen saturation, occurs. However, there is also a reduction in maximal cardiac output ( ) at altitude which offsets the increase in CaO₂ and, therefore, does not improve. The purpose of this investigation was to study the contribution of the increase in CaO₂ to the working muscles without the potentially confounding problem of a reduced . The approach used was to have seven male subjects (aged 17 to 24 years) perform one- and two-legged tests on a cycle ergometer at sea level (SL, PIO₂ = 159 Torr), after 1 h at 4300 m simulated altitude (SA, PIO₂ = 94 Torr) and during two weeks of residence on the summit of Pikes Peak, CO. (pP, 4300 m, PIO₂ = 94 Torr). Cardiac output limits maximal performance during two-legged cycling but does not limit performance during one-legged cycling. During the study, CaO₂ changed from 189±3 (mean ±SE) at SL to 161±4 ml·L^–1 during SA (SL vs. SA,p<0.01) and to 200±6 ml·L^–1 at PP (SL vs. PP,p<0.05; SA vs. PP,p<0.01). Two-legged decreased from 3.64±0.26 L·min^–1 at SL to 2.70±0.14 L·min^–1 during SA (p<0.01) to 2.86±0.16 L·min^–1 at PP (p<0.01). One-legged decreased from 2.95±0.22 at SL to 2.25±0.17 L·min^–1 during SA (SL vs. SA,p<0.01) but improved to 2.66±0.18 L·min^–1 at PP (SA vs. PP,p<0.05). Since only one-legged increased as more oxygen was made available to the working muscles, the altitude-induced reduction in can be implicated as being responsible for the reduction in during two-legged cycling.     

Acetylcholine-induced currents in acutely dissociated sympathetic neurons from adult hypertensive and normotensive rats have similar properties

Whole-cell patch-clamp recordings were used to compare the amplitude and kinetics of acetylcholine-induced currents (I _ACh) in acutely isolated superior cervical ganglion (SCG) neurons from spontaneously hypertensive (SHR) rats and Wistar-Kyoto (WKY) rats, to determine if altered postsynaptic transmitter responsiveness underlies the increased sympathetic nerve activity in SHR rat neurons. Rapidly activating and slowly inactivating inward currents were recorded in response to rapid application of ACh (5 M to 2 mM). Concentration/response relationships for SCG neurons isolated for SHR and WKY rats had dissociation constants of 161 M and 169 M, maximum responses of 26 nS/pF and 24 nS/pF, and Hill coefficients of 1.8 and 1.9, respectively. Activation of the currents was fitted well by a single exponential function with concentration-dependent time constants, whereas inactivation was fitted well by a double exponential function also with concentration-dependent time constants. The time constants of both activation and inactivation for SHR and WKY rats were not significantly different at any concentration tested. The results demonstrate that the postsynaptic effects of ACh are similar between SHR and WKY rat postganglionic neurons and, therefore, probably do not contribute to the observed differences in ganglionic transmission between SHR and WKY rat nerves.     

Parathormone as a mediator of inorganic phosphate diuresis during saline infusion in the rat

Summary Normal rats were infused with isotonic saline at 0.50 ml/min for 2 hours in order to expand their extracellular fluid volume. Under these conditions fractional excretion of inorganic phosphate was found to be as high as 38.8±3.0% of filtered phosphate, while fractional sodium excretion was 12.9±0.7% of filtered sodium. The combined addition of calcium and magnesium to the infusion solution decreased inorganic phosphate excretion significantly (P<0.001) to 11.2±3.6% (presumably by inhibiting parathyroid gland activity), while sodium excretion was unchanged (13.5±1.1%). Parathyroidectomized rats were infused with isotonic saline at 0.50 ml/min to achieve a similar extent of extracellular fluid volume expansion as in the normal rats. In these animals inorganic phosphate excretion was as low as 0.9±0.9% of filtered phosphate, while sodium excretion was 11.8±2.2% of filtered sodium. Administration of parathormone to volume expanded parathyroidectomized rats resulted in marked increases or inorganic phosphate excretion to 41.5±3.1% of filtered phosphate (P<0.001), while sodium excretion remained unaltered (12.0±2.8% of filtered sodium), thus resembling very closely the results in normal volume expanded rats.From these results it is concluded, that saline induced phosphaturia in normal rats is mediated primarily by parathormone. Furthermore, sodium excretion during volume expansion of extracellular fluid appears to be independent of inorganic phosphate excretion and independent of changes in parathyroid activity.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.     

Bedeutung der Mikroproteinurie zur Früherkennung hypertoniebedingter Endorganschädigungen

Summary To investigate the clinical importance of microproteinuria, we examined the prevalence of microproteinuria and its relation to cardiac structural adaptation in 80 male, middle-aged patients with essential hypertension. Patients with secondary causes of hypertension were ruled out.14 out of 80 hypertensives (18 percent) were found to have microproteinuria defined as negative for urinary protein excretion in the conventional test, but positive (above the upper normal limit) in the 24-hour urine samples. Patients with microproteinuria had a similar age and body weight, but a higher systolic and diastolic pressure (161±14/104±12 vs 148±14/97±9 mmHg,p< 0.02) and greater creatinine clearance (163±36 vs 136±33 ml/min,p<0.01) than those with normal protein excretion. Also, hypertensives with microproteinuria had a greater left ventricular mass (241±57 vs 207±45 g,p<0.05) and greater cross sectional area (22.2±2.8 vs 20.5±2.9 cm²,p< 0.05) evaluated by 2-D guided M-mode echocardiography than the control group. A positive Sokolow-index was more prevalent in patients with microproteinuria than in those without (x ²=6.2,p<0.02).Patients with essential hypertension and microproteinuria (prevalence 21 per cent) were characterized by a higher arterial pressure, by a higher degree of echocardiographic and electrographic evidence of left ventricular hypertrophy. Thus, microproteinuria might serve as a marker for early target organ damage in essential hypertension.

     

Enhanced excitatory junction potentials in mesenteric arteries from spontaneously hypertensive rats

Excitatory junction potentials (EJPs) were examined using intracellular recording techniques in mesenteric arteries isolated from 12- to 15-week-old spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and Sprague Dawley (SD) rats. The amplitudes of EJPs evoked by single supramaximal stimuli were larger in arteries from SHRs (12.9±0.7 mV,n=16) than in arteries from either WKYs (5.2±0.5 mV,n=24) or SDs (8.6±0.8 mV,n=15). The time constant of decay of EJPs did not differ significantly, suggesting that the passive electrical properties of the vascular smooth muscle are similar in the three rat strains. Spontaneous EJPs recorded in tissues from SHRs and WKYs had similar amplitude frequency distributions, suggesting that the quantal size is also similar between strains. In some arteries from SHRs, EJPs evoked by single stimuli triggered muscle action potentials (MAPs). Visible constriction only occurred following a MAP. In tissues from all three strains, summation of EJPs triggered MAPs. As EJPs are generated by the sympathetic co-transmitter adenosine 5-triphosphate (ATP), the findings of the present study indicate that purinergic transmission is enhanced in mesenteric arteries from SHRs, probably as a result of an increase in quantal release. A consequence is that when nerves are activated SHR arteries more readily undergo constriction that is dependent on voltage-activated Ca²⁺ influx.     

Sodium chloride as regulator of renal prostaglandin E2 production in patients with essential hypertension

Summary The effect of dietary sodium intake (5 days' low salt, 4 days' high salt) on 24-h urinary prostaglandin E₂ (PGE₂) and prostaglandin F₂ (PGF₂) excretion, blood pressure (BP), and plasma renin activity (PRA) was evaluated in 16 patients with essential hypertension. Sodium restriction significantly increased urinary PGE₂ excretion (p<0.05) from 151±76 to 328±94 ng/24 h, while high salt intake reduced renal PGE₂ production to 114±41 ng/24 h (p<0.05). There was a moderate but not significant increase in urinary PGF₂ excretion on the low salt regimen, which was reversed under high salt diet. Systolic and diastolic blood pressure fell from 162±11 to 145±10 mm Hg, i.e., 102±6 to 90±9 mm Hg on low sodium intake (35 mEq/day) and returned to levels close to control after 4 days on a high salt diet (250 mEq/day). Under low salt conditions, PRA increased significantly (p<0.001) from 0.83±0.33 to 2.82±1.12 ng AI/ml/h and fell to 0.45±0.31 ng AI/ml/h on high salt regimen (p<0.001).The results demonstrate that dietary sodium chloride intake modulates renal PGE₂ production in patients with essential hypertension. The depressed PGE₂ production under high salt conditions may play a role in regulation of renal vascular resistance and influence sustainment of chronic hypertensive disease.Supported by Deutsche Forschungsgemeinschaft     

Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat

Renal tubular bicarbonate reabsorption and acidification were evaluated in phosphate depleted rats (PD) and controls. After 33 days of phosphate depletion, urine pH of PD rats (N=5, 6.36±0.15) was significantly higher than control (N=5, 5.64±0.09,P<0.005) following an NH₄Cl load. Urinary titratable acid of PD rats (9.6±1.8) was significantly reduced compared to control (117.2±19.7 Eq/3 h,P<0.001), whereas NH ₄ ⁺ excretion was not different. The plasma HCO ₃ ^– thresholds at which bicarbonaturia occurred (approximately 25 mEq/l) were identical in controls and phosphate depleted rats during isotonic bicarbonate infusion. The higher urine pH of phosphate depleted rats following NH₄Cl administration was not due to low urinary phosphate as 3-day phosphate depleted rats could normally acidify urine after NH₄Cl (pH=5.86±0.09,N=6 vs. control 5.87±0.08,N=6,P=N.S.) despite urinary phosphate excretion as low as in 33-day PD rats. These data indicate the presence of impaired distal tubular acidification in chronically phosphate depleted rats.Former trainee of the Cardiovascular Research Program and currently a third year medical student at The University of Michigan Medical School.     

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.     

The source of urinary epidermal growth factor in humans

Summary To clarify the source of human urine EGF, we studied EGF renal clearance in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females during a 3 h study period. Plasma and urine creatinine and creatinine clearance were measured and calculated hourly. Mean (and SEM) creatinine clearance was similar in males and females (118±12 vs 105±6 ml/min). EGF was not detectable in plasma, whereas relatively high levels were measured in serum (2.5±0.25 vs 1.5±0.18 ng/ml in males and females respectivelyp<0.05). Urine EGF excretion averaged 1641±233 ng/h in males and 1507±191 ng/h in females (p>0.05). A significant correlation was observed between urine creatinine and urine EGF concentrations in both male (r = 0.98,p<0.01) and female (r=0.94,p< 0.01) subjects. EGF immunoreactivity in urine and serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr hEGF. Urine excretion of EGF approximated 1.5 g/h or 25 ng/mg creatine. The high concentrations of EGF found in urine in the face of non-detectable levels of EGF in plasma favor the hypothesis that EGF in urine is derived from kidney synthesis and secretion. The significant positive correlation between urine creatinine and urine EGF suggests a functional correlation between glomerular filtration and the process of tubular EGF excretion.Abbreviations EGF epidermal growth factor - hEGF human epidermal growth factor - IGF insulin-like growth factor - TGF alpha transforming growth factor - TGF beta transforming growth factor - NGF nerve growth factor - PDGF platelet derived growth factor - CPDA citrate phosphate dextrose adenine buffer - EDTA ethylenedinitrilotetraacetic acid - PBS phosphate saline buffer     

Diagnostic Accuracy and Visual Search Efficiency: Single 8 MP vs. Dual 5 MP Displays

This study compared a single 8 MP vs. dual 5 MP displays for diagnostic accuracy, reading time, number of times the readers zoomed/panned images, and visual search. Six radiologists viewed 60 mammographic cases, once on each display. A sub-set of 15 cases was viewed in a secondary study using eye-tracking. For viewing time, there was significant difference (F?=?13.901, p?=?0.0002), with 8 MP taking less time (62.04 vs. 68.99 s). There was no significant difference (F?=?0.254, p?=?0.6145) in zoom/pan use (1.94 vs. 1.89). Total number of fixations was significantly (F?=?4.073, p?=?0.0466) lower with 8 MP (134.47 vs. 154.29). Number of times readers scanned between images was significantly fewer (F?=?10.305, p?=?0.0018) with 8 MP (6.83 vs. 8.22). Time to first fixate lesion did not differ (F?=?0.126, p?=?0.7240). It did not take any longer to detect the lesion as a function of the display configuration. Total time spent on lesion did not differ (F?=?0.097, p?=?0.7567) (8.59 vs. 8.39). Overall, the single 8 MP display yielded the same diagnostic accuracy as the dual 5 MP displays. The lower resolution did not appear to influence the readers’ ability to detect and view the lesion details, as the eye-position study showed no differences in time to first fixate or total time on the lesions. Nor did the lower resolution result in significant differences in the amount of zooming and panning that the readers did while viewing the cases.     

Effects of diadenosine polyphosphates,ATP and angiotensin II on membrane voltage and membrane conductances of rat mesangial cells

Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap₃A), diadenosine tetraphosphate (Ap₄A), diadenosine pentaphosphate (Ap₅A) and diadenosine hexaphosphate (Ap₆A) on membrane voltage (V _m) and membrane conductance (g _m) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure V _m and g _m. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the V _m values in MC of WKY (–42±1 mV, n=70) and SHR rats (–45±2 mV, n=99) as well as in the agonist-induced changes of V _m, all data were pooled. The V _m of all the cells was –44±1 mV (n=169) and g _m was 15.9±1.8 nS (n=141). Ion-exchange experiments showed the presence of a K⁺ and a non-selective cation conductance in resting MC whereas a Cl^– conductance or a Na⁺selective conductance could not be observed. Ap₃A, Ap₄A, Ap₅A, AP₆A and ATP each at a concentration of 5 mol/l, led to a significant depolarization of V _m by 5±2 mV (n=14), 7±1 mV (n=25), 3±1 mV (n=23), 2±1 mV (n=16), and 14±2 mV (n=23), respectively. For Ap₄A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC ₅₀) as 6 mol/l (n=5–25), for ATP as 2 mol/l (n=9–37), and for Ang II as 8 nmol/l (n=6–18). Ap₄A 100 mol/l increased g _m significantly by 55±20% (n=16), 100 mol/l ATP by 135±60% (n=18). The diadenosine polyphosphates examined were able to depolarize V _m (Ang II >ATP> Ap₄A>Ap₃A>Ap₅A>Ap₆A) by activation of a Cl^– conductance and a non-selective cation conductance, as do ATP or Ang II.     

The influence of high carbohydrate diets on endurance running performance

Summary The purpose of the present study was to examine the influence of high carbohydrate (CHO) diets on recovery of endurance capacity following a treadmill run to exhaustion. Two high CHO diets were used, one in which the normal diet was supplemented with complex carbohydrates and the other in which supplementation was achieved with simple carbohydrates. The thirty recreational runners who took part in this study (fifteen men and fifteen women) completed weighed food intake diaries two to three weeks before the start of the study. From an analysis of this information each subject's normal diet was prescribed before Trial 1 and then a supplemented diet before Trial 2. The aim was to achieve an increase in carbohydrate content to 70% in the diets of the two high CHO groups and an equivalent increase in energy intake by the Control group. The subjects were required to run to exhaustion on a treadmill at a speed equivalent to 70% on two occasions separated by 3 days. After Trial 1 the subjects were divided into three equal groups. The Complex CHO group (301±86 mg vs 507±120 mg) and Simple CHO group (265±45 mg vs 462±81 mg) increased their CHO intake by approximately 70% (p<0.05) during the 3 days before Trial 2 whereas the Control group increased their energy intake with additional protein and fat so as to match the energy intakes of the two CHO groups. The Complex CHO group improved their running time to exhaustion during Trial 2 by 26% (105.9±22.4 to 133.3±46.5 min;p<0.01) and the Simple CHO group increased their run time by 23% (114.5±15.6 to 140.6±27.0 min;p<0.01) whereas there was no significant increase in the running time of the Control group (119±19.5 to 122.4±22.4 min). There was no significant difference between the blood lactate and glucose concentrations during the two trials but the plasma FFA concentrations were significantly lower before Trial 2 for the Complex CHO group (0.41±0.15 vs 0.27±0.16 mmol^–1;p<0.01) and the Simple CHO group (0.24±0.13 vs 0.19±0.09 mmol^–1). The respiratory exchange ratios for the two CHO groups were significantly higher for most of Trial 2 compared with the values obtained during Trial 1. The results of this study have shown that recovery of endurance running capacity is enhanced by an increase in dietary CHO, which can be accomplished by supplementing the normal diet with either simple or complex carbohydrates.     

GM-CSF counteracts hemorrhage-induced suppression of cytokine-producing capacity

Objective and design: To study whether a treatment with the hematopoietic growth factor GM-CSF restores the attenuated ex-vivo cytokine-producing capacity of macrophages after sublethal hemorrhagic shock.Subjects: Male Sprague-Dawley rats.Treatment: 20 g/animal of recombinant murine GM-CSF after shock via arterial line.Methods: Hemorrhagic shock was established by pressure-controlled bleeding to a mean arterial pressure of 50 mm Hg for 35–40 min and consecutive resuscitation. 24 h after hemorrhage, lipopolysaccharide (LPS)-induced cytokine production of isolated macrophages derived from different compartments was measured.Results: A significant reduction of LPS-induced TNF production was found in whole blood cultures (1.0 ± 0.7 ng/ml after sham vs. 0.23 ± 0.08 ng/ml after shock operation), macrophages derived from spleen (0.88 ± 0.23 ng/ml after sham vs. 0.03 ± 0.1 ng/ml after shock operation), peritoneum (2.2 ± 0.7 ng/ml after sham vs. 0.29 ± 0.4 ng/ml after shock operation) and bronchoalveolar fluid (0.65 ± 0.13 ng/ml after sham vs. 0.003 ± 0.027 ng/ml after shock operation, mean ± S.D.). In cells from animals treated with GM-CSF a significantly enhanced LPS-induced TNF production in splenic, alveolar and peritoneal macrophages was found after shock compared to the cells derived from untreated animals (peritoneum: 289 ± 366 ng/ml TNF after shock vs. 2066 ± 94 ng/ml TNF after shock and GM-CSF; lung: 9 ± 12 ng/ml TNF after shock vs. 64 ± 17 ng/ml TNF after shock and GM-CSF; spleen: 58 ± 96 ng/ml TNF after shock vs. 548 ± 47 ng/ml TNF after shock and GM-CSF). Blood cultures collected from rats after hemorrhagic shock did not show a significant increase of TNF-production after GM-CSF treatment.Conclusion: Hemorrhagic shock caused a depression of the TNFa response to LPS which was partly counteracted by treatment with GM-CSF. Therefore, GM-CSF represents a promising approach to normalise trauma- and shock-induced immune dysfunction.Received 4 April 2003; returned for revision 3 July 2003; accepted by A. Falus 25 August 2003