Bayou virus-associated hantavirus pulmonary syndrome in Eastern Texas: identification of the rice rat, Oryzomys palustris, as reservoir host

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute pancreatitis

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of alpha 2M-TRY activity in serum.     

Gabexate mesilate improves pancreatic microcirculation and reduces lung edema in a rat model of acute pancreatitis

We evaluated the effects of a protease inhibitor on the progression of acute pancreatitis in rats. The model was selected and modified to mimic an intermediate stage of the disease. The degree of microcirculatory derangement in the pancrease and of lung edema was determined to assess the effects of gabexate mesilate (ethyl-4-(6-guanidinohexanoyloxy) benzoate methane sulfonate), a synthetic antiprotease, in acute pancreatitis. Male Sprague-Dawley rats (225-275 g) were used. Experimental pancreatitis was established by four intramuscular injections of cerulein (50 micrograms/kg) at 1 hour intervals. Lipopolysaccharide (10 mg/kg) was injected intraperitoneally as an acute septic challenge. Gabexate mesilate was infused intravenously 6 hours after the initiation of induction of acute pancreatitis at doses of 0.01, 0.1, 1, or 10 mg/kg/h. Microcirculatory changes in the pancreas were studied using in vivo microscopy. All animals survived until the end of the experiments. Gabexate mesilate significantly improved pathologic criteria and decreased serum lipase levels at doses of 1 and 10 mg/kg/h. It significantly lessened the severity of lung edema and improved the microcirculatory environment in the pancreas by increasing flow velocity and reducing leukocyte sticking. These results indicate the beneficial effects of gabexate mesilate on pancreatic microcirculation and lung edema in the progression of acute pancreatitis with septic challenge in rats.     

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It was established while experiments on dogs that in an acute pancreatitis the vessels reactivity is changing, the tissue blood flow and oxygen pressure (pO2) are lowering in pancreatic tissue. Infusion of trental and thiotriazolinum didn't impede the tissue blood flow lowering but reduced significantly the oxygen consumption by pancreatic tissue.     

Isovolemic hemodilution with dextran 60 as treatment of pancreatic ischemia in acute pancreatitis. Clinical practicability of an experimental concept

OBJECTIVE: This phase-I study transferred the concept of isovolemic hemodilution, which has been proven beneficial in the treatment of experimental acute pancreatitis to the patient. SUMMARY BACKGROUND DATA: Pancreatic ischemia represents one main mechanism in the pathogenesis of necrotizing pancreatitis. Isovolemic hemodilution with dextran 60 has been shown experimentally to limit the progression of pancreatic necrosis by improving pancreatic microcirculation. METHODS: Thirteen patients with clinically severe nonbiliary pancreatitis and CT-classification E according to Balthazar were enrolled. Exclusion criteria were anemia, coronary heart disease, chronic obstructive pulmonary disease, coagulopathies, and secondary referral. The volume of blood to be exchanged for dextran 60 was calculated from a nomogram based on body surface. Isovolemic hemodilution aimed at a hematocrit of 30%. Independent from the exchange procedure conventional fluid resuscitation was performed to adjust the central venous pressure at 6 +/- 2 mm Hg. RESULTS: Whole blood (750-1,700 mL) was exchanged for dextran 60 during 45 to 70 minutes. No adverse effect was encountered; central hemodynamics were not affected. Considering a mean Ranson score of 5, mortality was low (7.7%). Progression of pancreatic necrosis was registered in only two patients subsequently undergoing surgical treatment (15%). CONCLUSIONS: Isovolemic hemodilution is practicable in patients. A randomized trial has to prove whether isovolemic hemodilution can substantially alter the course of acute pancreatitis as anticipated from animal studies.     

Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation

OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. STUDY DESIGN: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. RESULTS: Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.     

Effects of high dose octreotide on retrograde bile salt-induced pancreatitis in rats

The effects of somatostatin and octreotide (a long acting somatostatin analogue) in acute pancreatitis are inconclusive. This study examined the prophylactic and therapeutic effects of different doses of octreotide on retrograde sodium taurodeoxycholate-induced acute necrotizing pancreatitis in rats. The rats were divided into 4 groups receiving subcutaneous injection of saline, octreotide 10 microg/kg, 20 microg/kg at 0, 8 and 16 h and octreotide 20 microg/kg at 5, 13 and 21 h, separately. The serum levels of amylase and lipase, pancreatic histopathology, mortality and hemodynamics were examined. Octreotide significantly reduced serum levels of amylase and lipase at 12 h and the degree of pancreatic edema, necrosis and hemorrhage at 18-24 h as compared to the control group. Prophylactic octreotide 10 microg/kg significantly decreased the 24-h mortality from 100% to 44.4% (p < 0.05). The 24-h mortality further reduced to 12.5% and 10% with prophylactic and therapeutic octreotide 20 microg/kg, respectively. The decrease of mean arterial pressure at 12 h was significantly lower in octreotide groups than in the control group. We conclude that octreotide improves pancreatic histopathology and survival in acute necrotizing pancreatitis in rats.     

Pancreatic GAPDH gene expression during ontogeny and acute pancreatitis induced by caerulein

Recent studies indicated that expression of the housekeeping gene GAPDH is highly regulated during proliferation and differentiation. The objective of this study was to characterize by Northern blot the GAPDH mRNA expression in rat pancreas development and regeneration following acute pancreatitis induction by caerulein. Pancreatic GAPDH mRNA levels were the highest between fetal day 19 and the 11 postnatal day; they decreased to their lowest level after weaning on day 26. In acute pancreatitis, GAPDH mRNA levels were clearly increased 18 h after its initiation, were maximal during the first two days of induction and then decreased to control values after 9 days. These data demonstrate that overexpression of GAPDH may be implicated in pancreatic development, maturation and pancreas regeneration after acute pancreatitis.     

Effects of endothelin-1 on renal microvasculature measured using quantitative ultrasound

Renal vascular resistance is an important feature of kidney function and disease. To maintain adequate blood flow, renal vascular resistance varies in response to changes in systemic pressure. Vascular resistance is largely determined by arteriolar diameter, which is regulated by local and systemic factors. We used quantitative ultrasound techniques to follow renal vascular changes in anesthetized dogs during local intraarterial infusion of a potent vasoconstrictor, endothelin-1 (ET-1). Average arteriolar diameters were estimated by analyzing echo-signal spectra (5-15 MHz) obtained from renal cortex in vivo before, during, and after ET-1 infusion. At calculated arterial concentrations of 0.01 nM, 0.1 nM, and 1.0 nM, ET-1 reduced the average arteriolar diameter of 38 +/- 2 microns by 2%, 63%, and 91%, respectively, without producing a significant change in systemic blood pressure. Changes in scatterer size were consistent with the observed changes in renal hemodynamics detected using Doppler techniques. In addition, acoustic attenuation was found to increase with ET-1 concentration. These data suggest that quantitative ultrasound methods are sensitive to changes in renal arteriolar diameter, and may be a new noninvasive method for continuously monitoring changes in vascular resistance.     

Comparison of angiotensin converting enzyme and renin inhibition in rats following myocardial infarction

Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure.     

Blood concentrations of polymorphonuclear leucocyte elastase and interleukin-6 are indicators for the occurrence of multiple organ failures at the early stage of acute pancreatitis

We studied potential indicators of severe acute pancreatitis by measuring the blood concentrations of various cytokines, polymorphonuclear leucocyte elastase (PMN-E), acute phase reactants, pancreatic amylase (P-AMY), pancreatic elastase-1 (E-1) and white blood cell (WBC) counts in patients with acute pancreatitis. In addition, the presence of multiple organ damage was assessed. Subjects consisted of 22 patients with acute pancreatitis including severe (n = 11), moderate (n = 4) and mild (n = 7) cases. A significant positive correlation was observed between the number of organs damaged and the peak concentrations of interleukin (IL)-6, PMN-E, C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI). Among these markers, blood concentrations of PMN-E and IL-6 rapidly increased and peaked at the early phase of acute pancreatitis whereas CRP and PSTI did not. The elevation of PMN-E and IL-6 was greater the more severe the symptoms. However, no significant correlation was observed between the number of organs damaged and the maximum serum concentrations of P-AMY and E-1, or the WBC count, which have been considered to be markers of pancreatitis. These results suggest that PMN-E and IL-6 concentrations are useful indicators of severity and prognosis and their determination facilitates the selection of appropriate treatment in the early stages of disease to prevent the aggressive progression of acute pancreatitis.     

The first British reference preparations of cholera vaccine (Inaba) and of cholera vaccine (Ogawa)

We examined the visceral blood flow distribution during infusion of three vasodilators at doses that produced similar depression of systemic arterial pressure. The studies were performed in pentobarbital-anesthetized dogs using the radioactive microspheres technique. Minoxidil did not alter renal, total visceral, or visceral organ flow distribution with the exception of a modest increase in relative stomach blood flow. Nitroprusside increased the percentage of total visceral flow to the spleen and the hepatic artery. Dopamine increased blood flow to the stomach, intestine, and kidney. After phenoxybenzamine, the augmentation of stomach blood flow by dopamine was greatly increased, while blood flow to the splenic, pancreatic, and hepatic arteriolar vascular beds decreased. The decreases in blood flows may be due to decreased perfusion pressure in the absence of active vasodilation or to myogenic or metabolic autoregulation. Thus, at equivalent hypotensive responses, the vasodilator compounds that we studied produced markedly different patterns of visceral blood flow.     

Effect of angiotensin II antagonist infusion on autoregulation of renal blood flow

The role of the renin-angiotensin system in the autoregulation of renal blood flow was examined in the anesthetized dog. The angiotensin II antagonist, [1-sarcosine, 8-isoleucine]angiotensin II, was continuously infused into the renal artery at rates of 1 and 3 mug/min, and renin secretion rate and intrarenal distribution of blood flow as well as total renal blood flow were measured during acute reductions in renal perfusion pressure within and below the range of autoregulation. Renal autoregulation and redistribution of blood flow by pressure reduction were not disturbed by the angiotensin II antagonist. This result does not provide any evidence for a primary role of the renin-angiotensin system in renal autoregulation. Redistribution of blood flow by pressure reduction occurred independently of the renin-angiotensin system. It might depend on the differences in the resting tone among the zones.     

Protective effect of N-acetyl-L-cysteine on the renal failure induced by inferior vena cava occlusion

BACKGROUND: Renal ischemia is produced during orthotopic liver transplantation when the inferior vena cava is clamped above the renal veins (inferior vena cava occlusion [IVCO]), and it often leads to postoperative renal failure. Although free radicals and nitric oxide (NO) have been implicated in the pathogenesis of ischemic renal failure, the effect of free radical scavengers in this model is unknown. METHODS: The effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, on the acute renal failure that follows IVCO were evaluated in pentobarbital-anesthetized dogs. The effect of NO synthesis inhibition with NG-nitro-L-arginine methyl ester (NAME) was also studied. Renal vascular endothelial function was tested by infusing acetylcholine (Ach) into the renal artery before the ischemia and during reperfusion. RESULTS: Renal failure developed during IVCO and persisted during reperfusion in all groups. However, in NAC-pretreated dogs, the glomerular filtration rate recovered progressively, reaching 31% of basal preischemic values 150 min after reperfusion. During reperfusion, fractional excretion of sodium increased above preischemic values only in the control group, which indicates a beneficial effect of NAC and NAME on the tubular dysfunction observed during reperfusion. The renal response to Ach was abolished in control dogs and in animals given NAME during reperfusion, which indicates endothelial dysfunction. However, in NAC-pretreated dogs, the renal response to Ach was preserved during reperfusion. CONCLUSIONS: These results demonstrate that NAC ameliorates the renal failure and renal endothelial dysfunction induced by IVCO. This protective effect was abolished by NAME, which suggests that NO is involved in the beneficial effects of NAC. These data also suggest that the use of NAC could be beneficial in ameliorating the acute renal failure observed after orthotopic liver transplantation.     

Physical training alters the pathogenesis of pacing-induced heart failure through endothelium-mediated mechanisms in awake dogs

BACKGROUND: Beneficial effects of exercise training on cardiovascular function in chronic heart failure (CHF) have been suggested previously, but the underlying mechanisms are unknown. We tested whether daily exercise training improves systemic hemodynamics and preserves endothelium-mediated vasodilator function during development of heart failure. METHODS AND RESULTS: Fifteen dogs were surgically instrumented for hemodynamic measurements. One group of dogs underwent 4 weeks of cardiac pacing (210 bpm for 3 weeks and 240 bpm during week 4), and another group underwent pacing plus daily exercise training (4.4+/-0.3 km/h, 2 h/d). Pacing-alone dogs developed CHF characterized by typical hemodynamic abnormalities, blunted endothelium-mediated vasodilator function in coronary and femoral circulations, and decreased gene expression of endothelial constitutive nitric oxide synthase (ECNOS, normalized to GAPDH expression; normal, 1.15+/-0.31 versus CHF, 0.29+/-0.08, P<.05). Exercise training preserved normal hemodynamics at rest, endothelium-mediated vasodilator function, and gene expression of ECNOS (0.72+/-0.16 versus normal, P=NS). Inhibition of NO synthesis (nitro-L-arginine) in exercise-trained dogs abolished the preserved endothelium-mediated vasodilation of epicardial coronary arteries and elevated left ventricular end-diastolic pressure (7.7+/-0.3 to 19+/-3.4 mm Hg, P<.05), suggesting that the preservation of resting hemodynamics was in large part due to preserved endothelial function concealing the underlying CHF state. CONCLUSIONS: Long-term exercise training altered the natural history of heart failure due to rapid cardiac pacing. One of the underlying mechanisms is through the preservation of endothelial vasodilator function.     

Renal hemodynamics in the rat before and during inhibition of angiotensin II

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.     

Aneurysm clips: evaluation of MR imaging artifacts at 1.5 T

PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium, causes profound renal vasoconstriction by binding to ET-A receptors. The present study examined the renal actions of ET-1 after ET-A receptors were blocked by BE-18257B to unmask the functions of ET-B receptors. MATERIALS AND METHODS: Renal hemodynamics and clearance measurements were obtained in anesthetized dogs after intrarenal infusion of BE-18257B at 100 ng./kg./min. (Group 1), after intrarenal infusion of ET-1 at 2 ng./kg./min. (Group 2), or after intrarenal infusion of ET-1 superimposed on BE-18257B (Group 3). RESULTS: In Group 1, BE-18257B infusion did not alter arterial pressure, renal blood flow (RBF), GFR or tubular function. In Group 2, ET-1 infusion led to a significant decrease in RBF and GFR (37 and 40%, respectively) without altering arterial pressure. Urinary volume and sodium excretion were not changed but osmolality decreased significantly. In Group 3, BE-18257B infusion significantly attenuated the decrease in RBF caused by ET-1 and increased GFR by 40% without altering arterial pressure, associated with significant diuresis and natriuresis. CONCLUSION: Renal vasoconstriction caused by ET-1 is attenuated by ET-A receptor blockade with BE-18257B, which unmasks the hemodynamic and tubular actions of ET-B receptors. As a result, it limits the ET-1 induced decrease in RBF and raises GFR, and leads to a diuresis and natriuresis.     

Leukotriene receptor blockade in experimental heart failure

The pathophysiological role of endogenous leukotrienes in cardiovascular control and the regulation of renal function in congestive heart failure is not known. Therefore, in six conscious dogs with or without heart failure induced by right ventricular pacing (270/min, 10 days) we studied the effects of the leukotriene receptor antagonist FPL55712 on hemodynamics, plasma hormones and renal function. In healthy dogs, FPL55712 (1 mg kg-1 + 0.01 mg kg-1 min-1 i.v.) had little effect on hemodynamics, only reducing heart rate by 11% and insignificantly increasing systemic vascular resistance. Plasma levels of norepinephrine (-57%), renin (-30%) and aldosterone (-24%) were significantly decreased. Renal function parameters were not changed. In dogs with heart failure, FPL55712 significantly increased systemic vascular resistance (+16%) and decreased cardiac output (-15%). Plasma hormone levels were not changed, but renal plasma flow was decreased (-13%) and glomerular filtration rate (+12%), renal vascular resistance (+13%) and filtration fraction (+23%) were increased. It is concluded that there is no evidence for a contribution of endogenous leukotrienes to the systemic vasoconstriction in experimental heart failure. Whether the increase in systemic and renal vascular resistance induced by the leukotriene antagonist in dogs with heart failure reflects a role for endogenous leukotrienes with vasodilator action is still unclear and deserves further investigation.     

Poisoning with methanol and ethylene glycol:1H NMR spectroscopy as an effective clinical tool for diagnosis and quantification

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.     

Carbohydrate-based probes for detection of cellular lectins

Molecular mechanisms associated with apoptosis in pancreas remain largely unknown. Clusterin mRNA is induced in several tissues in response to most apoptotic stimuli. In these tissues, clusterin has an antiapoptotic activity. The aim of this work was to test whether clusterin, which is not expressed in normal pancreas, was induced in pancreas during pancreatitis and pancreatic development. Clusterin mRNA levels were strongly increased 6 h after pancreatitis induction. Maximal expression happened between 24-48 h and decreased progressively to undetectable levels at day 5. Clusterin mRNA was expressed with similar intensity in oedematous caerulein-induced pancreatitis and in response to various degrees of necrohaemorrhagic taurocholate-induced pancreatitis, indicating a maximal gene activity in all types of pancreatitis; in situ hybridization showed that the acinar cells and some ducts expressed clusterin mRNA. A single band of about 35-38 kDa was detected by western blot in pancreatic homogenates and in pancreatic juice from rats with acute pancreatitis, but not from control rats. Clusterin mRNA expression was strong in late fetal life and remains high until day 11 post-partum, then decreased progressively with a minimum from 35 to 90 days post-partum. Clusterin mRNA levels were strongly induced in pancreatic acinar AR4-2J cells in response to various apoptotic stimuli (i.e., cycloheximide, staurosporine, ceramide and H2O2) but not with interleukin (IL)-1, IL-4 or IL-6 or heat shock, which do not induce apoptosis in AR4-2J cells. In conclusion, we demonstrated that clusterin is synthesized and released by the pancreas. Its strong expression during acute pancreatitis suggests its involvement in the pancreatic response to injury. Clusterin is also induced during pancreatic development. Because these situations are associated with apoptosis and clusterin was shown to protect against apoptosis, we speculate that clusterin could be involved in the control of acinar cell apoptosis.