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Background: Indices of central arterial stiffness, derived by use of applanation tonometry, have shown to be strong independent predictors of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the intra- and inter-observer and day-to-day reproducibility of pulse-wave analysis (PWA) and pulse-wave velocity (PWV) in pre-dialysis patients with CKD stages 3-5 using applanation tonometry with the SphygmoCor software and hardware., Methods: Double recordings of the radial pressure waveform and the aortic and brachial PWV were performed under standardized conditions in 19 CKD patients with a mean GFR 25.3 ml/min/1.73 m(2) (range 9.9-42.2) by two trained observers and repeated by one of the observers within a week., Results: The mean inter-observer and day-to-day differences (+/-2 SD) for the augmentation index (AIx) were 0.9 +/- 15.8% and 2.6 +/- 11.2%, for subendocardial viability ratio (SEVR) -0.9 +/- 15.5% and -0.4 +/- 24.7%, for aortic pulse pressure (PP) 1.4 +/- 13.3 mmHg and 0.3 +/- 20.9 mmHg and for aortic PWV 0.3 +/- 3.2 m/s and -0.7 +/- 1.9 m/s, respectively. Intra-observer differences were calculated for each of three sets of double measurements and showed good reproducibility as well. Calculations on sample size needed in a clinical trial showed a limited number of patients needed in a clinical study over time., Conclusions: PWA and PWV based on applanation tonometry using the SphygmoCor software and hardware are highly reproducible in pre-dialysis patients with CKD with the day-to-day variation being in accordance with the intra- and inter-observer variation. Thus, applanation tonometry using the SphygmoCor system is a simple, non-invasive method to assess central haemodynamics in clinical trials in patients with pre-dialysis CKD with only a limited number of patients needed to detect significant differences.

The formation and fate of sulfide in a force main and a downstream-located gravity sewer were investigated in an extensive field study. Sulfide formation in the force main was significant. However, during 14 minutes of transport in the gravity sewer, the sulfide concentration decreased 30%, on average. An application of a conceptual sewer process model for simulating the formation and fate of sulfide was demonstrated. Overall, the model predicted that approximately 90% of the decrease of the sulfide concentration in the gravity sewer was the result of sulfide oxidation and that only a small fraction entered the sewer atmosphere, causing odor and corrosion. Even so, the model predicted concrete corrosion rates of up to 1.2 mm/y in the gravity sewer section.

The activity of hydrogen sulfide oxidizing bacteria within corroded concrete from a sewer manhole was investigated. The bacteria were exposed to hydrogen sulfide starvation for up till 18 months, upon which their hydrogen sulfide oxidizing activity was measured. It was tested whether the observed reduction in biological activity was caused by a biological lag phase or by decay of the bacteria. The results showed that the bacterial activity declined with approximately 40% pr. month during the first two months of hydrogen sulfide starvation. After 2-3 months of starvation, the activity stabilized. Even after 6 months of starvation, exposure to hydrogen sulfide for 6 hours a day on three successive days could restore the bacteriological activity to about 80% of the initial activity. After 12 months of starvation, the activity could, however, not be restored, and after 18 months the biological activity approached zero. The long-term survival aspect of concrete corroding bacteria has implications for predicting hydrogen sulfide corrosion in sewer systems subject to irregular hydrogen sulfide loadings, e.g. as they occur in temperate climates where hydrogen sulfide often is a summer-problem only.

Kinetics and stoichiometry of aerobic chemical and biological sulfide oxidation in wastewater from sewer networks were studied. In this respect, the effects of temperature and pH were investigated in the ranges 10 to 20 degrees C and 5 to 9, respectively. The temperature dependency of sulfide oxidation kinetics was described using an Arrhenius relationship. The effect of pH on the rate of chemical sulfide oxidation is related to the dissociation of hydrogen sulfide (H2S) to hydrogen sulfide ion (HS(-)), with HS(-) being more readily oxidized than H2S. Biological sulfide oxidation exhibited the highest rates at ambient wastewater pH, and the reaction was inhibited at both low and high pH values. Chemical sulfide oxidation was found to produce thiosulfate and sulfate, while elemental sulfur was the main product of biological sulfide oxidation. Based on the investigations, general rate equations and stoichiometric constants were determined, enabling the processes to be incorporated to conceptual sewer process models.

Objective: Applanation tonometry for pulse-wave analysis (PWA) and determination of pulse-wave velocity (PWV) is a non-invasive method for assessment of the central aortic pressure waveform and indices of arterial stiffness. The objective of this study was to examine the influence of eating and smoking on PWA and PWV measurements in order to establish standard examination conditions. Furthermore, intra- and interobserver reproducibility and the effects of varying the site of measurements were observed., Material and Methods: Duplicate measurements of the radial pressure waveform and of the brachial and aortic PWV on the right and left side of the body were recorded in 23 healthy subjects by two trained observers. Measurements were performed in the fasting state and 3 h after a high-calorie meal, and before and 1 h after smoking a cigarette., Results: Intake of a high-calorie meal as well as smoking caused significant changes in both PWA and PWV parameters and an inter-arm difference was observed. Intra- and interobserver reproducibility was good., Conclusions: Pulse-wave measurements by applanation tonometry should be undertaken in the same arm during fasting and smoking abstinence.

Sulfide buildup in sewer networks is associated with several problems, including health impacts, corrosion of sewer structures and odor nuisance. In recent years, significant advances in the knowledge of the major processes governing sulfide buildup in sewer networks have been made. This paper summarizes this newly obtained knowledge and emphasizes important implications of the findings. Model simulations of the in-sewer processes important for the sulfur cycle showed that sulfide oxidation in the wetted biofilm is typically the most important sink for dissolved sulfide in gravity sewers. However, sulfide emission and thereby potential hydrogen sulfide buildup in the sewer atmosphere is of particular importance in sewers constructed with large diameter pipes, in sewers constructed with steep slopes and in sewers conveying low pH wastewater. Precipitation of metal sulfides is only important when the sulfide concentration in the wastewater is low; i.e. less than 1 g Sm(-3).

Background: Patients reaching end-stage renal disease experience debilitating fatigue, with progression of this disease, rendering patients dysfunctional in their everyday lives., Methods: In vivo measurements of muscle function, assessed using surface electromyography (EMG), were made on 25 patients prior to and after a session of hemodialysis (HD) treatment, along side in vitro measurements of muscle function in isolated rat muscles incubated in normal or uremic conditions approximating to those found in uremic rats (rat uremic: RU) or uremic humans (human uremic: HU)., Results: HD significantly affected plasma values, e.g. reducing urea (69%), creatinine (62%), potassium (23%) and phosphate (48%) concentrations in patients (all p < 0.01). Treatment also improved the EMG frequency of 2nd dorsal interosseous (fast-twitch) (p < 0.01), although no change was noted for vastus lateralis (slow-twitch). In isolated rat muscles, a uremic environment had no significant effect on slow-twitch soleus during field stimulation, however, in fast-twitch extensor digitorum longus, a significant 23% (RU) and 22% (HU) faster rate of decline in force was measured, compared to controls (p < 0.001 and p < 0.01, respectively)., Conclusion: It is concluded that (1) muscle weakness and its electrophysiological correlates may be rapidly induced by uremic solutes and rapidly reversed when the solutes are removed by dialysis, and (2) fast-twitch muscles are more readily affected by uremic conditions than slow-twitch muscles., (Copyright 2006 S. Karger AG, Basel.)

Kalanchoë blossfeldiana varieties with orange, pink, red and magenta flowers were found to contain 3,5-O-beta-D-diglucosides of pelargonidin, cyanidin, peonidin, delphinidin, petunidin and malvidin. Pink, red and magenta varieties contained relatively high amounts of quercetin based flavonols. Four distinct quercetin flavonols were identified, namely quercetin 3-O-beta-D-glucoside and three that were quercetin 3-O-alpha-L-rhamnoside based, with either glucose, xylose or arabinose attached to position 2 of the rhamnose. In addition, the presence of at least three kaempferol based diglycosides was suggested from LC-MS analyses. Orange varieties contained very low amounts of flavonol co-pigments and of delphinidin derivatives. The flower extracts of the varieties 'Diva' (magenta) and 'Molly' (red) had identical anthocyanin ratios but differed significantly in flavonol content. The magenta variety contained four times as much quercetin relative to anthocyanidin as the red variety. This difference was mainly due to a larger content of quercetin 3-O-(2''-O-beta-D-glucopyranosyl-alpha-L-rhamnopyranoside). Based on pigment and co-pigment analyses, approaches for molecular breeding towards blue flower colour are discussed.

Oxidation of sulfide under aerobic conditions by biofilms grown on municipal wastewater in 6 identical pipe reactors was investigated. The biofilms were grown at pH 7.6 and temperatures of 20 and 25 degrees C under aerobic-anaerobic transient conditions with pulse dosing of sulfide in the bulk water. The pulse dosing of sulfide served to simulate conditions in a gravity sewer located downstream of a pressure main. During growth of the biofilms, sulfide was pulse dosed in concentrations of 0, 0.5, 2.0 and 5.0 g Sm(-3) with a frequency of 1h(-1). Based on a series of batch experiments, kinetics and stoichiometry of sulfide oxidation by the sewer biofilms was investigated and a rate equation and a stoichiometric constant proposed. Sulfide oxidation kinetics was significantly faster for biofilms grown at sulfide loadings of 0.5, 2.0 and 5.0 g Sm(-3)h(-1) than for biofilms grown in the absence of sulfide. However, the kinetics of sulfide oxidation was relatively constant for biofilms grown at sulfide loadings above 0.5 g Sm(-3)h(-1). Mass balance calculations of dissolved oxygen and sulfur compounds suggested the oxidation product to be elemental sulfur. Further oxidation of elemental sulfur could not be documented.

Wastewater quality characteristics in terms of biomass, its substrates, and the corresponding kinetic and stoichiometric parameters were determined based on 109 wastewater samples originating from five different campaigns in four different sewer networks. Quality parameters were determined by model calibration of measured wastewater oxygen uptake rates applying a model that describes the aerobic breakdown of wastewater organic matter. Thereafter, the distributions of the parameters were analyzed. Two of the five datasets were obtained at the upstream end of a five-km-long, intercepting gravity sewer. For each of these upstream wastewater samples, downstream samples were collected with a delay corresponding to the residence time. The upstream distributions of the wastewater composition were used as boundary conditions for a Monte Carlo simulation. The calculated downstream distributions were compared to the measured downstream distributions and good agreement was observed.

Objective: There may be advantages in using magnetic resonance imaging (MRI) in small-bowel disease. The aims of this study were to optimize the MRI examination technique and to evaluate the capabilities of MRI compared with those of conventional enteroclysis (CE)., Materials and Methods: MRI and CE were performed in 36 patients suspected of Crohn's disease. Based on 26 pilot studies optimal oral administration of plum juice and bulk fibre laxative was found. T2-weighted and gadolinium enhanced T1-weighted images were obtained using a breath-holding technique and butylscopolamine. Virtual endoscopy was performed. Conventional enteroclysis entailed duodenal intubation and administration of barium and air. Two radiologists evaluated the examinations independently. Finally, each patient scored the degree of discomfort, and preference for either MRI or CE was found., Results: The MRI technique ensured sufficient distension of the small bowel and small-bowel changes were found in 12 patients. In 3 patients this was not seen on conventional enteroclysis, which did not reveal any pathology that was not already seen on MRI. Pathological abdominal changes were found in 70% more patients during MRI than during conventional enteroclysis (p < 0.001). Endoscopic examination corresponded with the MRI findings. The examination quality decreased with increasing age (p = 0.002) and the interobserver agreement of the pathological changes was high (p < 0.001). Virtual endoscopy resulted in excellent demonstration of the mucosal surface. The examination discomfort scores obtained during the MRI were lower than those during conventional enteroclysis (p < 0.001)., Conclusions: MRI using the current technique is preferable to conventional enteroclysis because of superior demonstration of the entire small-bowel pathology, low level of patient discomfort and absence of radiation exposure.

Metabolon formation and metabolic channeling in plant secondary metabolism enable plants to effectively synthesize specific natural products and to avoid metabolic interference. Channeling can involve different cell types, take advantage of compartmentalization within the same cell or proceed directly within a metabolon. New experimental approaches document the importance of channeling in the synthesis of isoprenoids, alkaloids, phenylpropanoids, flavonoids and cyanogenic glucosides. Metabolon formation and metabolic channeling in natural-product synthesis facilitate attempts to genetically engineer new pathways into plants to improve their content of valuable natural products. They also offer the opportunity to introduce new traits by genetic engineering to produce plant cultivars that adhere to the principle of substantial equivalence.

Transformations of organic matter, nitrogen and sulfur in sewers can be simulated taking into account the relevant transformation and transport processes. One objective of such simulation is the assessment and management of hydrogen sulfide formation and corrosion. Sulfide is formed in the biofilms and sediments of the water phase, but corrosion occurs on the moist surfaces of the sewer gas phase. Consequently, both phases and the transport of volatile substances between these phases must be included. Furthermore, wastewater composition and transformations in sewers are complex and subject to high, natural variability. This paper presents the latest developments of the WATS model concept, allowing integrated aerobic, anoxic and anaerobic simulation of the water phase and of gas phase processes. The resulting model is complex and with high parameter variability. An example applying stochastic modeling shows how this complexity and variability can be taken into account.

A model concept for prediction of sulfide buildup in sewer networks is presented. The model concept is an extension to--and a further development of--the WATS model (Wastewater Aerobic-anaerobic Transformations in Sewers), which has been developed by Hvitved-Jacobsen and co-workers at Aalborg University. In addition to the sulfur cycle, the WATS model simulates changes in dissolved oxygen and carbon fractions of different biodegradability. The sulfur cycle was introduced via six processes: 1. sulfide production taking place in the biofilm covering the permanently wetted sewer walls; 2. biological sulfide oxidation in the permanently wetted biofilm; 3. chemical and biological sulfide oxidation in the water phase; 4. sulfide precipitation with metals present in the wastewater; 5. emission of hydrogen sulfide to the sewer atmosphere and 6. adsorption and oxidation of hydrogen sulfide on the moist sewer walls where concrete corrosion may take place.

Two-dimensional fluid simulations of interchange turbulence for geometry and parameters relevant for the scrape-off layer of magnetized plasmas are presented. The computations, which have distinct plasma production and loss regions, reveal bursty ejection of particles and heat from the bulk plasma in the form of blobs. These structures propagate far into the scrape-off layer where they are dissipated due to transport along open magnetic field lines. From single-point recordings it is shown that the blobs have asymmetric conditional wave forms and lead to positively skewed and flattened probability distribution functions. The radial propagation velocity may reach one-tenth of the sound speed. These results are in excellent agreement with recent experimental measurements.

In this study, the kinetics and stoichiometry of chemical sulfide oxidation of wastewater from sewer networks were investigated. Based on experiments, it was shown that the stoichiometry could be considered identical for wastewater from two sampling sites. However, the kinetics differed significantly among the wastewaters from the two sites. Effects of pH and temperature were investigated in the pH and temperature ranges 5-9 and 5-25 degrees C, respectively. The rate of chemical sulfide oxidation could be related to the dissociation of H2S to HS-, with HS- being oxidized at a higher rate than H2S. The temperature dependency of the chemical sulfide oxidation rate was described using an Arrhenius relationship. The oxidation rate was found to double with a temperature increase of 12 degrees C. The stoichiometry of the chemical oxidation was not significantly affected by varying pH and temperature. Based on the experiments, a general rate equation, including a stoichiometric coefficient describing chemical sulfide oxidation in wastewater was proposed, enabling the process to be incorporated into sewer process models that can predict odor and corrosion problems.

A method for determination of kinetics and stoichiometry of chemical sulfide oxidation by dissolved oxygen (DO) in wastewater is presented. The method was particularly developed to investigate chemical sulfide oxidation in wastewater of sewer networks at low DO concentrations. The method is based on continuous measurement of the reactants allowing the kinetics to be determined at varying reactant concentrations during the course of the experiment. The kinetics determined was simulated by a rate equation. The precision of the method was assessed in terms of the standard deviation of the kinetic parameters determined in a triplicate experiment. The kinetic parameters determined in 25 experiments on wastewater samples from a single site exhibited good constancy with a variation of the same order of magnitude as the precision of the method. It was found that the stoichiometry of the reaction could be considered constant during the course of the experiments although intermediates accumulated. This was explained by an apparent slow oxidation rate of the intermediates. The method was capable of determining kinetics and stoichiometry of chemical sulfide oxidation at DO concentrations lower than 1 g of O2 m(-3).

The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid 133Xe injection method, whereas blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 h. Five groups of animals were studied: 1) nephrectomized dialyzed rats, 2) nephrectomized dialyzed rats given a single intravenous dose of the angiotensin-converting enzyme inhibitor captopril (10 mg/kg), 3) sham nephrectomized and dialyzed rats, 4) rats receiving drugs as dialyzed rats but no surgery, and 5) rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared with controls. Nephrectomy, captopril, sham operation, or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53 +/- 4 mmHg) and sham-operated (58 +/- 4 mmHg) rats compared with diet control rats (78 +/- 3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35 +/- 2 mmHg). Thus removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls.

Objective: The aim of the present study was to develop a rat model for in vivo studies of the local effects of the renin-angiotensin system (RAS) following elimination of circulating renin., Methods: Sprague Dawley rats were bilaterally nephrectomised and had a peritoneal dialysis catheter implanted. The rats were maintained on dialysis continuously for 48 hours, using Dianeal PD4 3.86% glucose dialysis solution. The peritoneal catheter and an automated system for dialysate exchange were made in our laboratory. A sham nephrectomised control group of rats was also dialysed., Results: Nephrectomised and sham-operated rats remained active and in good general condition during peritoneal dialysis. At 48 hours, in nephrectomised, dialysed rats, peritoneal urea clearance was 4.14+/-0.52 ml/hour, plasma urea was 40.0+/-7.7 mmol/L, plasma creatinine was 0.423+/- 0.070 mmol/L and plasma renin was below the limit of detection., Conclusions: In conclusion, it was possible to sustain bilaterally-nephrectomised rats on continuous peritoneal dialysis for 48 hours, pending elimination of renin from the circulation. The nephrectomised dialysed rat model should be useful for investigation of the physiological effects of the circulating versus the local RAS.

Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report describes a case of acute renal graft dysfunction following the addition of an ARB to existing ACE inhibition. This unmasked an unknown iliac artery stenosis. The case indicates a possible important role of Ang II generated by non-ACE pathways in this situation.

Angiotensin (Ang) II may modulate reproductive function in the bovine ovary. Therefore, expression and localization of a local ovarian renin-angiotensin system (RAS) were investigated by elucidating the influence of the estrus cycle, pregnancy, and the presence of follicular cysts. Receptor analysis and autoradiography were used to characterize and localize Ang II receptors. Cyclic variations in the density of ovarian Ang II receptors were found with a higher value in estrus than in diestrus. The density in ovaries with follicular cysts was in the same order of magnitude as in estrus. The Ang II receptor type 2 (AT(2)) dominated in all three groups. Autoradiography showed that the majority of antral follicles and follicular cysts had intense AT(2) receptor binding in the theca externa. Binding was less intense in the theca interna, whereas there was no binding in the granulosa layer. In the corpora lutea, the AT(2) receptor was dominant in the capsule and in connective tissue infoldings, whereas no binding was observed in the luteal tissue. The type 1 Ang II receptor (AT(1)) was dominant in the stroma and showed no cyclic changes. Angiotensin-converting enzyme (ACE) activity was detected in all aspirated follicular fluids and homogenates of ovarian tissue. Autoradiography showed that most of the ACE was localized on endothelial cells. Renin immunoreactivity was found in granulosa and thecal cells of antral follicles and in luteal cells. Furthermore, solitary cells in the stroma, presumably macrophages, displayed intense staining. Our finding of cyclic changes support the concept of an active and regulated RAS in the bovine ovary.

The expression of the angiotensin-forming enzymes, renin and angiotensin-converting enzyme (ACE), were examined in the bovine uteroplacental unit. The ACE activity was determined in cell membrane fractions, and ACE and renin were localized by autoradiography and immunohistochemistry, respectively. In the myometrium, the ACE activity was significantly higher in dioestrous than in oestrous. ACE activity correlated negatively with the day of gestation in the endometrium and myometrium but positively in the placentome and allantoamniotic membrane. Autoradiography showed, that ACE was localized in vascular endothelial cells in all compartments. ACE was also expressed in the endometrial stroma and uterine glands, most pronounced in the outer part of the basal zone. In the intercotyledonary membrane and the placentome, the mesenchymal cells located near the trophoblast cells expressed ACE. Solitary macrophage- or monocyte-like cells showing intense renin immunoreactivity were found in the uterus, while the uterine and the glandular epithelial cells displayed inconsistent reactivity. No renin was observed in the placentomes or in the fetal membranes. The findings demonstrate a regulated expression of angiotensin-forming enzymes throughout the bovine uteroplacental unit. Whether this local renin-angiotensin system contributes to the highly regulated morphological and functional changes throughout the oestrous cycle and gestation remains to be established., (Copyright 2001 Harcourt Publishers Ltd.)

Background: The aim of the study was to evaluate the uricosuric effect of the angiotensin II receptor antagonist, losartan, in hypertensive patients with renal transplants who are treated with cyclosporin A (CsA)., Methods: Twenty-six patients with stable renal function and hypertension, 16 men and 10 women, median age 47 years (range, 25-63 years), were studied in an open randomized crossover trial, comparing a 2-week control period with a 2-week period of once-daily administration of 50 mg of losartan. The main outcome measurements were fractional excretion of uric acid (FE(uric acid)) based on 24-hr urine collections and plasma uric acid., Results: The median FE(uric acid) was 5.7% (range, 2.4-10.4%) in the control period with a median change of +0.84% (range, -1.15% to +2.77%) in the losartan period (P<0.0002). Plasma uric acid was 0.47 mM (0.29-0.69 mM) in the control period with a change of -0.03 mM (-0.10 to 0.06 mM) in the losartan period (P<0.002). Diastolic blood pressure was 87 mmHg (70-97 mmHg) in the control period with a change of -3 mmHg (-13 to +6 mmHg) in the losartan period (P<0.005). There was no difference in systolic blood pressure between the two study periods. Plasma creatinine was 165 microM (102-356 microM) in the control period with a change of +9 microM (-36 to +60 microM) in the losartan period (P<0.01). Plasma potassium was 4.2 mM (3.0-4.7 mM) in the control period with a change of + 0.2 mM (-0.2 to +0.9 mM) in the losartan period (P<0.0005)., Conclusions: Once-daily administration of 50 mg of losartan in hypertensive CsA-treated patients with renal transplants caused a 17% increase in FE(uric acid) and an 8% fall in plasma uric acid.

1. Plasma concentrations of prorenin were determined in a transgenic animal model of nephropathy induced by overexpression of transforming growth factor (TGF)-beta1 in the juxtaglomerular apparatus. 2. In both female and male mice, plasma concentrations of prorenin were higher in transgenic than in non-transgenic animals. In sexually mature mice, plasma prorenin concentrations were higher in males than in females in both transgenic and non-transgenic animals in accordance with a sexual dimorphism of the plasma concentration of prorenin. 3. The results indicate that TGF-beta1-like androgens increase prorenin secretion in the kidneys and may explain the increased plasma prorenin concentrations in patients with diabetic nephropathy.

The evolution of vortex statistics for decaying two-dimensional turbulence in a square container with rigid no-slip walls is compared with a few available experimental results and with the scaling theory of two-dimensional turbulent decay as proposed by Carnevale et al. Power-law exponents, computed from an ensemble average of several numerical runs, coincide with some experimentally obtained values, but not with data obtained from numerical simulations of decaying two-dimensional turbulence with periodic boundary conditions.

The components of the renin-angiotensin system (RAS) are expressed in the uteroplacental unit. The expression varies between species, probably due to the marked species differences in placental architecture. The conditions for angiotensin (Ang) II formation exist and Ang II receptors are present throughout the human uteroplacental unit, indicating the presence of a functional local RAS. The uteroplacental RAS interacts with other regulatory systems and in this way modulates various aspects of tissue function. It is suggested that the uteroplacental RAS is important for the regeneration of the endometrium after shedding, and for decidualization, implantation and placentation. The RAS participates in the regulation of the uteroplacental blood flow, prostaglandin synthesis and oestradiol secretion. Disturbances of the uteroplacental RAS may lead to dysfunctional bleeding and to reduced uteroplacental blood flow in pregnancies complicated by pre-eclampsia and intrauterine growth retardation., (Copyright 2000 Harcourt Publishers Ltd.)

In normal valvular collagen turnover in the rat, angiotensin (Ang) II and angiotensin-converting enzyme (ACE) seem to be involved. In common human and canine valvular diseases, changes in valvular collagen play a pathogenetic role and the valvular renin-angiotensin system is therefore of particular interest in these species. Healthy mitral valve leaflets and adjacent left ventricular myocardium were taken from five rats and five dogs immediately after euthanasia, and from five humans at autopsy. The valvular and myocardial Ang II receptors and ACE were detected and measured by quantitative autoradiography. In rat valves, high levels of Ang II receptors and ACE were found. In human and canine valves, insignificant levels were found. Significant myocardial levels of Ang II receptors and ACE were found only in the rat. The study demonstrated major species differences regarding the level of valvular and myocardial Ang II receptors and ACE in man, dog and rat. The lack of valvular Ang II receptors and ACE in man and dog, suggest that the renin-angiotensin system plays a minor, if any, role in the physiological valvular collagen formation in these two species. The findings in humans, however, need to be confirmed using fresh material.

The present study was undertaken to characterize, determine and localize angiotensin II receptors in the nonpregnant and pregnant bovine uterus. In addition, the concentration of active renin, which is responsible for the generation of angiotensin, was determined. Autoradiography and angiotensin II receptor binding studies showed that all compartments of the bovine uterus contained high concentrations of angiotensin II receptors. In general, the type 1 angiotensin II receptor (AT1) predominated over the AT2 receptor. In the endometrium, the highest density was found in the caruncles and the AT1 receptor was always predominant. The density of angiotensin II receptors in the endometrium increased at the beginning of pregnancy, but decreased and reached values similar to those in nonpregnant animals near term. In the myometrium, the density of angiotensin II receptors was highest at or near the endometrial-myometrial junction. In this area, the predominant type of angiotensin II receptor in the uterus of cyclic cows varied, whereas the AT1 receptor always predominated during pregnancy. Non-AT1 and non-AT2 binding sites were found in the same locations as the angiotensin II receptors, but at lower densities. With the exception of the pregnant endometrium, all compartments contained higher active renin concentrations than found in plasma, indicating local synthesis of renin. This study demonstrates a difference in the expression of types of angiotensin II receptor in the bovine uterus compared with other species. The high densities of angiotensin II receptors localized in several important areas imply that the renin-angiotensin system participates in regulation of growth and tissue function in the bovine uterus.

Our purpose was to elucidate the hypothesis that paracrine-produced transforming growth factor (TGF)-beta1 regulates the accumulation of extracellular matrix (ECM) in renal glomeruli, a hallmark of diabetic nephropathy. To produce TGF-beta1 from the juxtaglomerular apparatus in mouse kidneys, we cloned a mouse Ren-1c promoter fragment (-4.100 to +6 base pairs) upstream of porcine TGF-beta1 (pTGF-beta1) cDNA, mutated to ensure secretion of biologically active TGF-beta beta1. The resulting transgenic mice had significantly more TGF-beta1 in their kidneys than was in those of nontransgenic controls, as confirmed by immunohistochemistry, and the production of TGF-beta1 was enhanced in vivo by captopril-induced stimulation of the Ren-1c promoter. Overproduction of pTGF-beta1 close to the glomerulus resulted in a local accumulation of ECM, composed partly of collagen type IV and laminin, and thickening of the basement membrane, characteristic features of diabetic nephropathy. Interstitial accumulation of ECM and signs of tubular atrophy were present only in older mice (>5 months of age). Results from in situ hybridization and immunohistochemistry suggest that pTGF-beta1 stimulated the production of endogenous TGF-beta1 along collecting ducts and connecting tubules. The increased amount of biologically active TGF-beta1, transgenic as well as endogenous, was corroborated by heightened proteoglycan synthesis from incubated kidney slices. This transgenic model demonstrates that sustained local expression of TGF-beta1 leads to glomerulopathy. We conclude that autocrine- or paracrine-produced TGF-beta1 may play a role in the development of glomerular diseases, such as diabetic nephropathy.

Autoradiography and angiotensin (Ang) II receptor binding studies showed that all parts of the bovine placenta and fetal membranes contained high densities of Ang II receptors throughout gestation. The receptors were predominantly subtype 2 (AT2) receptors in the fetal and subtype 1 (AT1) receptors in the maternal compartment. In the allantoamnionic membrane, Ang II receptors were evenly distributed in the mesenchymal tissue, with the highest expression around the few arteries. In the intercotyledonary and cotyledonary allantochorionic membrane, AT2 receptors as well as the less-expressed AT1 receptors were located on mesenchymal cells, especially adjacent to the allantoic endoderm, trophoblast cell layer, and arteries. In the mesenchymal tissue of the placentome, Ang II receptors were mostly expressed at the main branches of the fetal villi of the cotyledons. In the maternal part of the placentome, mainly AT1 receptors but also low densities of AT2 receptors and non-AT1/non-AT2 Ang II binding sites were found close to the stalk and at the main branches of the maternal crypts. Autoradiography revealed no changes in the pattern of distribution of the Ang II receptors throughout gestation. It is suggested that Ang II has an effect on regulatory as well as growth processes in these tissues.

Irreversible damage of renal transplants may be prevented if insufficient graft perfusion can be detected perioperatively. Colour and spectral Doppler ultrasonography were performed in 30 consecutive renal transplants. The perfusion of the graft and the Resistive Index (RI) were evaluated perioperatively (perioperatively and less than 15 min postoperatively) and 24 h after the operation in all patients. In four cases (13.3%) RI > 0.9 was detected and immediate surgical correction of the cause led to a normalization (RI < 0.8) in all four cases. A RI < 0.9 required no intervention in 26 cases (86.7%). All renal grafts in this series were functioning 1 month postoperatively. In a comparative group, 30 consecutive transplants carried out at our institution without perioperative Doppler ultrasonography evaluation, a loss of four renal grafts perioperatively was recorded retrospectively. We conclude that perioperative ultrasonography Doppler evaluation may provide an easy applicable and reliable method for early detection of insufficient renal graft perfusion, allowing surgical correction before irreversible damage of the graft occurs. RI > 0.9 is pathological. A continuation of the study is required to clarify the long-term value of perioperative Doppler ultrasonography graft monitoring.

1. The aim of the present study was to characterize the angiotensin II (AngII) receptor subtypes in the porcine uterus and the variation of receptor densities and renin concentrations during gestation. 2. In myometrium from non-pregnant sows, the AngII receptors were almost exclusively AT2 receptors. During gestation, the AngII receptor density was decreased and the AT1 receptor became predominant in the last part of gestation as a result of a down-regulation of the AT2 receptor. 3. In the endometrium, the AT1 receptor was predominant both in non-pregnant sows and throughout gestation. The AngII receptor density was decreased during gestation as a consequence of down-regulation of the AT1 receptor. 4. The renin concentrations in the myometrium and endometrium of pregnant sows did not differ from those in non-pregnant animals. 5. The finding of enzymatically active renin and high densities of AngII receptors in the porcine uterus is in accordance with a functional renin-angiotensin system (RAS), which may be important for an increased vascular permeability and stimulated angiogenesis in early pregnancy and for contraction of the myometrial smooth muscle cells during parturition. The predominance of AT1 receptors in the endometrium of non-pregnant sows differs from an earlier finding in non-pregnant women, where AT2 receptors were predominant in the endometrium. This is in accordance with earlier studies, indicating species differences in the expression and possibly also the physiological roles of the RAS in reproductive tissues.

The relationship between follicular fluid concentrations of oestradiol (E2) and progesterone (P4), and follicular wall tissue renin concentrations and in-vitro secretion rates was investigated. The follicular fluid concentrations of prorenin correlated negatively with oestradiol and the E2/P4 ratio, and positively with progesterone in accordance with earlier findings. The high concentrations of active renin and prorenin in the follicular wall tissue, and the secretion rates of both active renin and prorenin all correlated positively with oestradiol and the E2/P4 ratio, but negatively with progesterone. These findings suggest that atretic follicles have higher follicular fluid renin concentrations but lower tissue renin concentrations and in-vitro secretion rates than healthy non-atretic follicles. The high follicular fluid prorenin concentrations in atretic follicles are most likely caused by a high prorenin secretion rate earlier in the oestrus cycle. The existence of relationships between the follicular fluid steroids and the follicular wall concentrations and secretion rates of active renin and prorenin indicates an interaction between the reninangiotensin system and steroidogenesis, but it may also reflect regulation by common factors, such as gonadotropins.

The present study was undertaken in order to characterize and determine angiotensin (Ang) II receptors and renin in the porcine placenta and fetal membranes. High densities of Ang II receptors of subtype 2 (AT2 receptors) were demonstrated in all parts of the placenta and fetal membranes throughout gestation. AT1 receptors (subtype 1) were only found in the first part of the gestation and only in the allantochorion-endometrium at low densities. The total Ang II receptor density was increased in the allantochorion-endometrium in the last stage of gestation. Except for this finding the Ang II receptor density did not vary during gestation. Some of the highest receptor densities were found in the allantoamnionic membrane. The Ang II receptor densities did not correlate with the duration of the gestation in any part of the placenta. Enzymatically active renin was found in all parts of the porcine placenta and fetal membranes in concentrations similar to those found earlier in the blood plasma. The renin concentrations did not correlate with the Ang II receptor densities or the duration of the gestation in any part of the placenta. Compared with the human placenta, where the Ang II receptors are almost exclusively AT1 receptors and low receptor densities are found in the fetal membranes, the present results indicate profound species differences in the expression and function of the renin-angiotensin system in the placenta and fetal membranes.

The expression of angiotensin (Ang) II receptors, active renin and prorenin in porcine and bovine ovarian follicles and corpora lutea was investigated and compared. In the wall tissue of porcine follicles, the Ang II receptor density was 47 (range 19-97; n = 13) fmol/mg membrane protein. The active renin concentration was 1.32 (0.40-3.43; n = 23) GU/kg wet tissue. These values were about 35-fold and 15-fold lower, respectively, than previously found in bovine follicles. No prorenin could be detected in the porcine follicular wall tissue. Ang II receptors of subtype 2 (AT2 receptors) with a dissociation constant (Kd) of 1.01 (0.64-1.79; n = 8) nmol/l for [Sar1-Ile5-Ile8]-Ang II were demonstrated in the bovine corpus luteum. The receptor density was 22.7 (1.9-93; n = 26) fmol/mg membrane protein, which was about 10-fold higher than in porcine corpora lutea. The active renin concentration was 20.7 (2.2-60.0; n = 26) GU/kg tissue in bovine and 0.40 (0.16-1.09; n = 17) GU/kg tissue in porcine corpora lutea. No prorenin could be detected in corpora lutea from both species. The variation between species in expression of the ovarian renin-angiotensin system indicates the existence of species differences in the physiological role.

The regulation of angiotensin (Ang) II receptor expression in ovarian follicles was reviewed. Ang II receptor expression, assessed as the Ang II binding capacity, varied with the animal species and the developmental stage of the follicle. In cows, the expression correlated positively with follicular size and negatively with the active renin concentration in the follicular wall tissue. No relations were found to the follicular fluid concentrations of prorenin, estradiol or progesterone. In cell cultures, luteinizing hormone up-regulated Ang II receptor expression in cows, whereas it was decreased by follicle-stimulating hormone, Ang II and testosterone in rats. These data support the concept of an active and regulated RAS in ovarian follicles. The species differences in Ang II expression suggest varying functional roles of the RAS between species.

Color Doppler sonography is a new reliable and noninvasive diagnostic method in the evaluation of varicocele testes. Thirty-two persons (14 with varicoceles and 18 controls) participated in the investigation. We found two different graphs (spectral analysis) in men with varicoceles testis during the Valsalva's manoeuvre. Semen analysis from these males with varicocele was compared with an age-matched control group without varicocele. The analysis revealed significant difference in qualitative motility and qualitative motility after 24 hours but no significant difference in other parameters of semen quality. There were significant difference in the normal semen morphology but no difference in abnormal forms among the two groups. We did not find a spectral picture that could predict a compromised sperm quality in the varicocele group. These data show that the color doppler is an important tool in the detection of a varicocele. It is important for the patient to understand the Valsalva's manoeuvre and we suggest that all males being evaluated in an infertility clinic undergo a color doppler scan with and without the Valsalva's manoeuvre and that a spectral analysis be performed to locate even small varicoceles.

1. The aim was to analyse the in vivo variations with time of prorenin and active renin and their relationship to steroid hormones in ovarian follicular fluid during follicular growth in heifers. 2. Thirty one beef heifers were assigned to two groups after oestrous synchronization: an unstimulated and a follicle-stimulating hormone (FSH)-treated (superovulated) group. Within each group, animals were slaughtered at different times of the follicular phase of the oestrous cycle. Ovarian follicular fluids were aspirated and analysed for the concentrations of active renin, prorenin, oestradiol-17 beta (E2) and progesterone (P4). 3. Prorenin and active renin concentrations in follicular fluid remained constant until the luteinizing hormone (LH) peak, after which time they increased four- and two-fold, respectively, in superovulated heifers. 4. In follicular fluid, prorenin and active renin correlated negatively with oestradiol and E2/P4 ratio but positively with progesterone during follicular growth in superovulated heifers. Prorenin also correlated negatively with oestradiol and E2/P4 ratio in unstimulated heifers. 5. The increase of renin concentrations in ovarian follicles after the LH peak and the correlations to steroid hormones suggest an important role of the ovarian renin-angiotensin system in bovine follicular growth and maturation.

1. The ovarian follicular renin-angiotensin system was investigated by using an in vitro incubation method, based on tissue incubation of individual bovine follicles. 2. Very high and varying concentrations of active renin (median 18.0 GU/kg, range 2.1-107 GU/kg; n = 101) and prorenin (11.7 GU/kg, range < 2.6-142 GU/kg; n = 101) existed in unincubated ovarian follicular tissue. 3. Active renin and prorenin increased 35 and 959%, respectively, in follicular wall tissue and incubation medium during 72 h of in vitro incubation. The protein synthesis inhibitor cyclohexamide inhibited active renin and prorenin formation. No activation of prorenin occurred in incubation medium or follicular fluid in vitro. Active renin was degraded during incubation. 4. Primarily prorenin but also active renin were secreted into the incubation medium. Secretion was directed both to the internal and external surface of the follicular wall. 5. Follicle-stimulating hormone (FSH) slightly stimulated the synthesis and secretion of prorenin in vitro. 6. The synthesis and secretion rates of active renin and prorenin varied markedly between individual follicles. 7. The finding of very high and varying concentrations of active renin in follicular wall tissues together with the formation and secretion of active renin during in vitro incubation provide further evidence for an active and regulated renin-angiotensin system in ovarian follicles.

1. The purpose of this study was to investigate angiotensin II (AII) receptors in isolated bovine ovarian follicles and the relationship of their density to follicular concentrations of prorenin, active renin, oestradiol and progesterone. 2. Displacement of [125I]-[Sar1-Ile5-Ile8]-AII binding by the AII receptor antagonists PD 123319 and Losartan (DuP 753) confirmed that follicular AII receptors are of subtype 2 (AT2 receptor). 3. The dissociation constant (Kd) for [Ile5]-AII (human AII) was 0.84 (range 0.51-1.47) nmol/L. The receptor density varied between 90 and 5990 (mean 1640) fmol/mg membrane protein. 4. The follicular AII receptor density correlated positively with follicular diameter (Spearman's rho = 0.518; P < 0.003) and tissue weight (Spearman's rho = 0.636; P < 0.0001), and negatively with the active renin concentration in the follicular wall (Spearman's rho = -0.399; P < 0.02). The AII receptor density did not correlate with the follicular fluid concentrations of prorenin, active renin, oestradiol (E2), progesterone (P4) or the E2/P4 ratio. The follicular fluid concentrations of prorenin correlated negatively with the E2/P4 ratio (Spearman's rho = -0.716; P < 0.0001). 5. The inverse relationship between AII receptor density and the high active renin concentrations in the follicular wall suggests an active regulated tissue renin-angiotensin system. A high AII receptor density is a general feature of large bovine ovarian follicles.

Evidence has accumulated for the existence of local tissue renin-angiotensin systems in the reproductive tissues. In the ovary the local renin-angiotensin system (RAS) has been shown to influence ovulation and steroidogenesis. In this review we focus on aspects of a local RAS in the uteroplacental unit. High renin concentrations have been found in all tissues of the uteroplacental unit. The presence of renin mRNA in the endometrium, choriodecidua and the fetal part of the placenta indicates local renin synthesis. Angiotensin (Ang) II, formed by the enzymatic action of tissue renin and Ang I converting enzyme, acts by interaction with its receptors. These receptors have been demonstrated in high densities in the placenta and uterus, indicating an autocrine or paracrine action of Ang II. Several probable effects of the uteroplacental RAS can be defined. It is very likely that the uteroplacental RAS plays an important role during implantation and placentation by stimulation of decidualization and angiogenesis. Furthermore, Ang II may regulate synthesis and secretion of other hormones formed locally in the uteroplacental unit. During labour the action of Ang II may be important for contraction of the uterine musculature, Ang II is also involved in the complex regulation of the uteroplacental blood flow. Species difference in the expression of the uteroplacental RAS exists, and one may speculate that the physiological and pathophysiological roles vary between species.

1. High concentrations of prorenin and active renin were previously found in ovarian follicular fluid from cattle but not from pigs. In the present study female reproductive tissues and fluids from cattle and pigs during gestation were investigated to clarify a possible species difference in active renin and prorenin concentrations. 2. Very high concentrations of active renin but no prorenin were found in corpus luteum from both species. 3. Relatively low concentrations of active renin, in the same order as in maternal blood plasma, were found in myometrium, endometrium, placenta and fetal membranes from both species. Prorenin was undetectable in these tissues except for bovine myometrium and porcine endometrium in some animals. 4. The concentrations of active renin and prorenin in amnionic fluid from both species were below the maternal plasma values. In allantoic fluid the concentrations were higher than in amnionic fluid. 5. The plasma concentrations of active renin and prorenin did not change during gestation in pigs. This finding is in contrast to the observations in humans and does not support a systemic effect of prorenin during gestation. 6. The presence of renin in the reproductive tissues, especially the very high concentrations in the corpus luteum, indicates a local function of the renin-angiotensin system during gestation.

Objectives: The aim was to demonstrate whether prorenin is present in plasma from 24-h nephrectomized rats. Its existence and concentration is currently under debate., Design: Determination of the 50% inhibition concentration (IC50) values for inhibition of plasma renin in intact and 24-h nephrectomized rats. The potent and specific rat renin inhibitor CH-732 was used., Methods: Our previously published method for the determination of rat prorenin was used. It is characterized by removal of an interfering trypsin-formed angiotensin I immunoreactive material before the renin incubation step., Results: The trypsin-activated prorenin-like activity of 24-h nephrectomized plasma was due only to a minor degree to real prorenin as judged by CH-732 inhibition. The major part of the prorenin-like activity was due to a hitherto unknown sulphydryl enzyme, which could be blocked by N-ethylmaleimide. In normal plasma all prorenin was real prorenin. The plasma concentration of real prorenin in 24-h nephrectomized rats was approximately 10% of that in intact rats., Conclusion: Prorenin is definitely present in nephrectomized plasma, but in low concentrations. The data support the concept that the major part of plasma prorenin in intact rats originates from the kidneys. The previously published values for prorenin in intact rats were correct, whereas those in 24-h nephrectomized rats were too high. If N-ethylmaleimide is added to our previously published method for rat prorenin, it overcomes the three known problems with prorenin determination in rat plasma: trypsin generation of angiotensin I immunoreactive material; trypsin destruction of angiotensinogen; and interference in trypsin-activated nephrectomized plasma of a sulphydryl enzyme, which generates an angiotensin-I-like material.

A case of acute uraemia caused by cholesterol emboli in the kidneys in a sixty-six year old male with arteriosclerosis is presented. No effective treatment is available, but recognizing the condition may save the patient from otherwise time-consuming extensive diagnostic programmes.

Alcoholic ketoacidosis is seen in chronic alcoholics who have been starving for days. This was the case in the present patient who had metabolic acidosis on admission. The differential diagnoses are primarily diabetic ketoacidosis, intoxication (salicylate, methanol, ethylene glycol and fenformin), lactate acidosis, hunger-induced ketoacidosis and uraemia. Treatment should consist of intravenous glucose and correction of the dehydration with isotonic sodium chloride.

1. In previous studies we have demonstrated and solved several methodological problems in relation to the measurement of prorenin by trypsin activation in rat, bovine, hog and horse plasma. 2. The aim of the present study was to develop a method for the measurement of prorenin in bovine and porcine ovarian follicular fluid. 3. Trypsin activation of follicular fluid generated angiotensin I immunoreactive material (AI IM) in both species. 4. The AI IM interfered with the renin assay, but could be completely removed by a cation exchange resin in a batch-wise technique. 5. The enzymatic activity of trypsin-activated prorenin and pre-existing active renin was completely inhibited by a specific inhibitor of renin. 6. The reactions were optimized and an accurate measurement of prorenin in ovarian follicular fluid was developed. 7. The existence of prorenin and renin in bovine ovarian follicular fluid was established. Prorenin and renin in porcine ovarian follicular fluid was demonstrated for the first time. 8. The ratio between ovarian follicular fluid and plasma was 43 for prorenin and 19 for active renin in cattle. The same ratios in pigs were 1.3 and 0.4, respectively. These findings indicate a species difference with respect to the amount of prorenin or active renin present in ovarian follicular fluid.

In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues.