Abstract The scope of this paper is to explore the benefits of both conventional operation design, co and counter-current, to propose a new alternative design for fixed bed catalytic reactor both steady state and the dynamic behavior were consider in the analisys. Additionally for the steady state, a study on the possible alternatives for the patterns of cooling fluid was also realized, searching for an efficient refrigeration as well as minimum energy cost for the fixed bed catalytic reactor. The results shows that the proposed alternative design for fixed bed catalytic reactor has considerable advance compared to conventional system

BACKGROUND AND PURPOSE Safe intraluminal access to the ureter and kidney is essential for endourologic procedures. Pharmacologic manipulation of ureteral smooth muscle could conceivably ease access and decrease morbidity. To minimize systemic effects, local intraluminal administration would be optimal, but the urothelium presents a barrier to the passage of medications. We present a novel ex-vivo apparatus and technique to measure ureteral peristalsis and assess drug diffusion. MATERIALS AND METHODS Excised 3-cm pieces of porcine or human ureters were placed inside a specially designed apparatus that allows separate manipulation of the intra- and extraluminal environments while measuring peristalsis. Intraluminal antegrade perfusion was maintained by a reservoir. A pressure transducer was placed at the inflow end of each ureter segment. After equilibration, phenylephrine (10 μM) was then added extraluminally to induce peristalsis. Nifedipine was then added to the intraluminal reservoir or the external organ bath. The concentration of nifedipine needed to cause aperistalsis was measured. RESULTS In 12 trials, extraluminal nifedipine caused aperistalsis at a concentration of 1 ± 0.1 μM, while intraluminal nifedipine needed 10.2 ± 1.1 μM. Significantly higher concentrations of nifedipine were needed intraluminally to cause aperistalsis, (P < 0.0001). CONCLUSIONS With our apparatus, we can control the intraluminal and extraluminal ureteral environments, and measure peristalsis before and after drug administration. This apparatus should help investigators who are interested in studying both the diffusion of a wide range of drugs, as well as the effects of those medications on ureteral physiology. In this study, the urothelium acted as a significant barrier to the diffusion of nifedipine.

1. The aim of the present study was to investigate the effects of simulated microgravity on the arterial dilatory responsiveness and L-arginine (L-Arg)-nitric oxide (NO)-cGMP pathway in the abdominal aorta of rats. 2. Twenty healthy male Sprague-Dawley were randomly divided into control and simulated microgravity groups. Rats in the simulated microgravity group were subjected to hindlimb unweighting (HU). After 4 weeks, arterial dilatory responsiveness was examined in vitro in isolated abdominal aortic rings. Western blotting was used to measure endothelial (e) and inducible (i) NO synthase (NOS) protein content. Total concentrations of nitrate and nitrite (NO(x)), the stable metabolites of NO, were determined by the chemiluminescence method. Nitric oxide synthase activity in the abdominal aorta was determined through the conversion of [(3)H]-L-Arg to [(3)H]-L-citrulline. 3. The data showed that the dilatory responses of the arterial rings to L-Arg and acetylcholine decreased in rats exposed to simulated microgravity, but the dilatory responses to sodium nitroprusside and 8-bromo-cGMP were similar in both simulated microgravity and control rats. The expression of eNOS and iNOS did not differ significantly between the two groups. The NO(x) concentration in the abdominal aorta of HU rats was significantly less than that in control rats. Nitric oxide synthase activity in the aorta decreased after 4 weeks of HU. 4. The data indicate that endothelium-dependent vasorelaxation in the abdominal aorta decreased due to 4 weeks of simulated microgravity in rats and that this impaired dilatory responsiveness may result from decreased NOS activity.

Hindlimb unweighting (HLU) of rats is a model used to mimic the cephalic fluid shift potentially involved in the orthostatic intolerance experienced by astronauts. Certain arteries in these rats exhibit a decreased contractile response to adrenergic agonists. It was shown previously that this may be caused by changes in thick filament regulation (Summers et al., Vascul Pharmacol 48: 208-214, 2008). In the present study, it was hypothesized that HLU also modifies thin filament regulation by effects on p38(MAPK) and ERK. Abdominal aorta rings from 20-day HLU rats and untreated controls were subjected to phenylephrine and phorbol 12,13-dibutyrate (PDBU) concentration response curves in the presence and absence of two inhibitors: the p38(MAPK) inhibitor SB-203580 and the MEK inhibitor U-0126. SB-203580 decreased control sensitivity to both agonists, but HLU sensitivity was not significantly affected. U-0126, which blocks enzymes immediately upstream of ERK, affected sensitivity to both agonists equally between control and HLU. Western blot analysis revealed no change in total levels of p38(MAPK) and its downstream target heat shock protein 27 but did reveal a decrease in phosphorylated levels of both after stimulation with PDBU and phenylephrine after HLU treatment. Neither total ERK nor phosphorylated levels after stimulation were affected by HLU. Total levels of caldesmon, a molecule downstream of both pathways, were decreased, but phosphorylated levels after stimulation were decreased by roughly twice as much. The results of this study demonstrate that HLU downregulates p38(MAPK), but not ERK, signaling. In turn, this may decrease actin availability for contraction.

Chronic renal failure (CRF) is associated with reduced physical activity, increased HTN, endothelial dysfunction, atherosclerosis and cardiovascular disease. Sedentary life style increases, whereas regular exercise reduces risk of cardiovascular disease in the general population. Study tested the hypothesis that aerobic exercise might improve arterial dysfunction in CRF rats. One week after 5/6 nephrectomy (CRF) or sham operation (control), rats were housed in regular cages or cages equipped with running wheels for 4 weeks. Thoracic aorta was harvested. Contractile response to potassium, phenylephrine, relaxation response to acetylcholine, sodium nitroprusside (SNP) and isoproterenol were determined. Compared to control animals, sedentary CRF animals exhibited significant azotemia, proteinuria, hypertension, increased sensitivity to potassium, phenylephrine, isoproterenol, reduced sensitivity to acetylcholine and sodium nitroprusside. Exercise CRF‐induced heightened sensitivity of aorta to phenylephrine and potassium, restored its sensitivity to acetylcholine without affecting arterial pressure or renal function. CRF results in heightened sensitivity to potassium‐ and alpha‐1 adrenergic mediated contractility and depressed sensitivity to endothelium‐dependent relaxation in aorta. Exercise training can improve vascular function in animals, and perhaps humans, with CKD.

Intraluminal exposure of the ureter to nifedipine and/or ketoprofen could prove beneficial by relaxing smooth muscle and inhibiting peristalsis. Omeros’ proprietary combination product candidate, OMS201, includes nifedpine and ketoprofen as active pharmaceutical ingredients and is designed to provide clinical benefits during endoscopic urological procedures by reducing smooth muscle contractions and inhibiting inflammation and pain. To evaluate the single agents as well as the OMS201 combination product, isolated naïve porcine ureters were cannulated and subjected to antegrade perfusion. Ten μM phenylephrine was added to the external medium to induce ureteral peristalsis. Addition of 0.3 μM nifedipine to external bathing medium resulted in a rapid aperistalsis in less than 5 minutes. In contrast, intraluminal perfusion with 9 μM nifedipine required 14 ±2.6 minutes to cause aperistalsis. Intraluminal ketoprofen, 27 μM, was without significant effect on amplitude or rate. The combination of nifedipine (9 μM) and ketoprofen (27 μM) in OMS201 was effective in reducing peristalsis, demonstrating the contribution of nifedipine to smooth muscle relaxation and inhibition of peristalsis. It is concluded that while the urothelial lining is a drug barrier, intraluminal 9 μM nifedipine can penetrate to the ureteral smooth muscle and fully inhibit peristalsis. Funded by Omeros Corp.

Hindlimb unweighting (HU) treatment in rats mimics the cephalic fluid shift experienced by astronauts in microgravity. It may also serve as a model for ground based orthostatic hypotension. It has been shown previously that the abdominal aorta of the HU rat exhibits a deficit in contractile capacity in response to adrenergic agonists. Wistar rats were subjected to 20 days of HU treatment and their abdominal aortas were removed and sectioned into 3 mm rings. These rings and those from paired with age matched controls were subjected to concentration‐contractile response curves to either U46619 or phenylephrine with and without the Rho kinase inhibitor, Y27632. Alternatively, rings were snap frozen after exposure to 1 μM U46619 or 1 μM phenylephrine and Western blot analysis was performed. HU treatment decreased contractile response to U46619, a known activator of the Rho Pathway and decreased the inhibitory effect of Y27632. Western blotting revealed decreased levels of RhoA after HU treatment as well as decreased phosphorylation of both the 110 Kd myosin light chain phosphatase regulatory subunit after phenylephrine stimulation and myosin light chain after both U46619 and phenylephrine stimulation. It is concluded that the RhoA‐Rho kinase pathway is altered in the abdominal aorta of the HU rat and this may contribute to the HU‐induced decrease in contraction. Funded by NASA Grant NN04CK29G.

You have accessJournal of Urology1 Apr 2008PUTTING THE URETER TO “REST”: THE EFFECTS OF NIFEDIPINE, KETOPROFEN, OR THE COMBINATION ON PHENYLEPHRINE ENHANCED PERISTALSIS IN AN EX VIVO INTRALUMINALLY PERFUSED PORCINE URETERAL MODEL Ralph E Purdy, Stan Shelkovnikov, Scott M Summers, Jeffrey M Herz, Clark E Tedford, Geoffrey N Box, Michael K Louie, and Ralph V Clayman Ralph E PurdyRalph E Purdy More articles by this author , Stan ShelkovnikovStan Shelkovnikov More articles by this author , Scott M SummersScott M Summers More articles by this author , Jeffrey M HerzJeffrey M Herz More articles by this author , Clark E TedfordClark E Tedford More articles by this author , Geoffrey N BoxGeoffrey N Box More articles by this author , Michael K LouieMichael K Louie More articles by this author , and Ralph V ClaymanRalph V Clayman More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)61649-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "PUTTING THE URETER TO “REST”: THE EFFECTS OF NIFEDIPINE, KETOPROFEN, OR THE COMBINATION ON PHENYLEPHRINE ENHANCED PERISTALSIS IN AN EX VIVO INTRALUMINALLY PERFUSED PORCINE URETERAL MODEL." The Journal of Urology, 179(4S), p. 561 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 561 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Ralph E Purdy More articles by this author Stan Shelkovnikov More articles by this author Scott M Summers More articles by this author Jeffrey M Herz More articles by this author Clark E Tedford More articles by this author Geoffrey N Box More articles by this author Michael K Louie More articles by this author Ralph V Clayman More articles by this author Expand All Advertisement PDF DownloadLoading ...

BACKGROUND:Chronic renal insufficiency (CRI) is associated with a high incidence of hypertension (HTN), endothelial dysfunction, atherosclerosis and cardiovascular disease. Sedentary life style increases, whereas regular exercise reduces the risk of cardiovascular disease. This study was designed to test the effect of regular exercise on vasodilatory and vasoconstrictive responses of the thoracic aorta in rats with renal mass reduction.METHODS:One week after 5/6 nephrectomy (CRI) or sham operation (control), rats were housed in either regular cages or cages equipped with running wheels for 4 weeks. Thereafter, thoracic aorta was harvested and contractile response to potassium and phenylephrine (PhE), and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were determined.RESULTS:Compared with the control animals, sedentary CRI animals exhibited significant azotemia, proteinuria, HTN, oxidative stress, and increased sensitivity to potassium and PhE, and reduced sensitivity to ACh and SNP. Exercise training for 4 weeks reduced oxidative stress, reversed CRI-induced heightened sensitivity of the aorta to PhE and potassium, and restored its sensitivity to ACh (but not SNP) without affecting arterial pressure or renal function.CONCLUSIONS:CRI results in heightened sensitivity to potassium- and alpha-1 adrenergic-mediated contractility and depressed sensitivity to endothelium-dependent relaxation in the aorta. Regular exercise improves these abnormalities without affecting arterial pressure or renal function. These observations suggest that exercise training can improve vascular function in animals, and perhaps humans, with chronic kidney disease.

BACKGROUND:Hindlimb unloading (HLU) is used to simulate microgravity in rats and has been shown to decrease contractile response in the abdominal aorta. The thoracic aorta has not been studied as thoroughly.METHODS:Wistar and Sprague-Dawley rats were subjected to HLU for 20 d and the thoracic aortas were isolated and sectioned into 3-mm rings for the measurement of isometric force development. Concentration response curves (CRCs) to phenylephrine (PHE) were obtained in endothelium-intact and -denuded rings from both strains of rats. Acetylcholine, methylfurmethide (MFM), and sodium nitroprusside (SNP) CRCs were obtained in the Wistar rats.RESULTS:HLU had no effect on the contractions of endothelium-intact Wistar aortas to PHE, but decreased the maximal PHE-induced contraction (2.82 +/- 0.16 g Control vs. 2.18 +/- 0.11 g HLU) in intact Sprague-Dawley aortas. After endothelium removal, HLU increased the contractions of Wistar, but not Sprague-Dawley, aortas to PHE (1.91 +/- 0.12 g Control vs. 2.95 +/- 0.13 g HLU). HLU had no effect on the relaxation to acetylcholine, but increased the sensitivity to the relaxing effects of MFM (LOG EC50 -6.96 +/- 0.12 Control vs.-7.31 +/- 0.17 HLU) and SNP (LOG EC50 -7.90 +/- 0.15 Control vs.-8.35 +/- 0.10 HLU) in the Wistar rats.SUMMARY:It is concluded that HLU increased smooth muscle contracting and endothelium-dependent relaxing capacities equally in the Wistar aortas, and had no effect on smooth muscle, but increased endothelium-dependent relaxation, in the Sprague-Dawley aortas.

The goal of this study was to determine the effects of microgravity on myofilament protein expression and both passive and active length-force relationships in carotid and femoral arteries. Microgravity was simulated by 20-day hindlimb unweighting (HU) in Wistar male rats, and carotid and femoral artery segments were isolated from both HU and control (CTL) rats for Western blot and length-force analysis. Western blots revealed that HU significantly decreased myosin light chain-20 (MLC-20) protein levels in both carotid and femoral arteries and decreased myosin heavy chain (MHC) in femoral artery. alpha-Actin levels were not altered by HU treatment in either artery. Length-force analysis demonstrated that HU did not change either passive or active length-force relationships in the femoral artery. HU-treated arterial rings developed significantly less force to 100 mM K(+) than CTL, but optimal lengths were identical. In the carotid artery, length-active force curves were identical for both CTL and HU; however the length-passive force curve for HU-treated rings exhibited a steeper slope than CTL, suggesting decreased compliance of the artery wall. In conclusion, our data suggest that the HU-induced decreases in both MLC-20 and MHC in femoral artery are responsible for the decreased contraction to 100 mM K(+) in HU-treated femoral artery rings. In the carotid artery, the HU-induced decrease in vessel wall compliance may counter any decrease in contractility caused by the decreased MLC-20 levels.

Responses of endothelium removed femoral arterial rings to vasoactive compounds were examined in vitro, and the expression of Myosin and Actin of femoral artery were observed by Western Blotting and Immunohistochemistry in hndlimb unweighting rats and control rats. The results showed that contractile responses of femoral arterial rings evoked by Phenylephrine, Endothelin-1, Vasopressin, KCl, Ca(2+) and Ca(2+) ionophore A23187 were decreased in hindlimb unweighting rats as compared with that of controls. But vasoddatory responses induced by SNPand cGMP were not different between groups. No significant differences have been found in expressions of Calponin, Myosin, Actin, and the ratio of MHC SM1/SM2 between the two groups, but expression of alpha-SM-Actin decreased in hindlimb unweighting rats. The data indicated that the diminished contractile responsiveness probably result from altered contractile apparatus, especially the contractile proteins.