The influence of feeding crimped kernel maize silage on broiler production, nutrient digestibility and meat quality.

Two experiments were carried out in parallel with male Ross 308 broilers over 37 d. An experiment with a total of 736 broilers was performed to study the effect of dietary inclusion of crimped kernel maize silage (CKMS) on broiler production and meat quality. Another study with 32 broilers was carried out from 21 to 25 d to investigate the inclusion of CKMS on nutrient digestibility. In both trials, 4 dietary treatments were used: wheat-based feed (WBF), maize-based feed (MBF), maize-based feed supplemented with 15% CKMS (CKMS-15) and maize-based feed supplemented with 30% CKMS (CKMS-30). Compared with MBF, the dry matter (DM) intakes of broilers receiving CKMS-15 and CKMS-30, respectively, were numerically 7.5 and 6.2% higher and feed conversion ratio 6 and 12% poorer (significant for 30% CKMS), although there were no significant differences in AME content between the three diets. At 37 d, the body weight of birds receiving 15% CKMS was similar to birds fed with MBF. However, the inclusion of 30% CKMS decreased broiler growth. Dietary supplementation with CKMS significantly reduced the apparent digestibility of phosphorus. The fat digestibility was significantly lower for CKMS-30 than for the other three diets. Broiler mortality decreased significantly when CKMS was added to the diet. The consumption of drinking water was significantly lower in all maize-based diets as compared to WBF and was lowest in broilers fed with CKMS-30. An improved litter quality in terms of DM content and a lower frequency of foot pad lesions was observed with broilers supplemented with both dietary levels of CKMS. The addition of CKMS to maize-based diets increased juiciness, tenderness and crumbliness of the meat. In conclusion, the dietary supplementation of 15% CKMS had no negative effect on broiler growth and positively influenced bird welfare in terms of mortality and foot pad health. Therefore, the addition of 15% CKMS to maize-based diets is considered an advantageous feeding strategy in broiler production.

Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study.

AIMS/HYPOTHESIS: Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c) and cardiovascular risk factors in type 2 diabetes. METHODS: Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements. RESULTS: Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049 ± 17,659 vs 27,270 ± 32,004 pmol/l × min (p = 0.838). In the placebo group AUC for insulin decreased from 27,392 ± 14,348 pmol/l × min to 22,938 ± 11,936 pmol/l × min (p = 0.002). Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for gastrin. HbA(1c) increased from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.3 ± 0.8% (56 ± 6 mmol/mol) in the esomeprazole-treated group and from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.4 ± 0.8% (57 ± 6 mmol/mol) in the placebo group (n = 21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No change in BP was seen in the patients treated with esomeprazole. CONCLUSIONS/INTERPRETATION: Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Glucagon and a glucagon-GLP-1 dual-agonist increases cardiac performance with different metabolic effects in insulin-resistant hearts.

BACKGROUND AND PURPOSE: The prevalence of heart disease continues to rise, particularly in subjects with insulin resistance (IR), and improved therapies for these patients is an important challenge. In this study we evaluated cardiac function and energy metabolism in IR JCR:LA-cp rat hearts before and after treatment with an inotropic compound (glucagon), a glucagon-like peptide-1 (GLP-1) receptor agonist (ZP131) or a glucagon-GLP-1 dual-agonist (ZP2495). EXPERIMENTAL APPROACH: Hearts from IR and lean JCR:LA rats were isolated and perfused in the working heart mode for measurement of cardiac function and metabolism before and after addition of vehicle, glucagon, ZP131 or ZP2495. Subsequently, cardiac levels of nucleotides and short-chain CoA esters were measured by HPLC. KEY RESULTS: Hearts from IR rats showed decreased rates of glycolysis and glucose oxidation, plus increased palmitate oxidation rates, although cardiac function and energy state (measured by ATP/AMP ratios) was normal compared with control rats. Glucagon increased glucose oxidation and glycolytic rates in control and IR hearts, but the increase was not enough to avoid AMP and ADP accumulation in IR hearts. ZP131 had no significant metabolic or functional effects in either IR or control hearts. In contrast, ZP2495 increased glucose oxidation and glycolytic rates in IR hearts to a similar extent to that of glucagon but with no concomitant accumulation of AMP or ADP. CONCLUSION AND IMPLICATIONS: Whereas glucagon compromised the energetic state of IR hearts, glucagon-GLP-1 dual-agonist ZP2495 appeared to preserve it. Therefore, a glucagon-GLP-1 dual-agonist may be beneficial compared with glucagon alone in the treatment of severe heart failure or cardiogenic shock in subjects with IR.

Advances in pemphigus research, signaling, and acantholysis.

Pemphigus is a family of human autoimmune blistering diseases in which pathogenic autoantibodies induce blistering in skin and mucosa. The mechanisms by which pemphigus autoantibodies induce disease in the skin is under active investigation. A large number of cellular events induced in the target keratinocytes by pemphigus IgG have been described and suggest that pemphigus IgG binding to desmogleins trigger a complicated cascade of intracellular signaling and regulatory events. Targeting these intracellular events may prove useful therapeutically.

Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes.

AIMS/HYPOTHESIS: Gastrin has been implicated in islet growth/neogenesis, and proton pump inhibitors (PPIs) have been shown to increase endogenous gastrin levels in animals and humans. Therefore, we investigated the effect of PPIs in a model of type 2 diabetes, Psammomys obesus. METHODS: P. obesus (morning blood glucose [mBG] 16.9 +/- 0.6 mmol/l) were treated with vehicle or different doses (1-15 mg/kg) of lansoprazole for 17 days. RESULTS: Treatment with lansoprazole resulted in up to ninefold dose-dependent increases in endogenous gastrin levels (p < 0.05 for 10 mg/kg lansoprazole vs vehicle). There was a significant reduction in mBG levels in all animals in the high-dose lansoprazole groups during the 17 day treatment period, whereas there was no significant improvement in mBG in animals in the vehicle groups. The mBG at end of study was 18.2 +/- 2.1, 8.7 +/- 2.2 (p < 0.01), and 6.1 +/- 2.3 (p < 0.001) mmol/l for vehicle and lansoprazole 10 and 15 mg/kg, respectively. The animals treated with 15 mg/kg lansoprazole, compared with vehicle, had a 2.3-fold increase in the intensity of insulin staining in beta cells (p=0.0002) and 50% higher beta cell mass (p=0.04). CONCLUSIONS/INTERPRETATIONS: The PPI lansoprazole had significant glucose-lowering effects in an animal model of type 2 diabetes, an effect that is most likely mediated through an increase in endogenous gastrin levels.

ZP120 causes relaxation by pre-junctional inhibition of noradrenergic neurotransmission in rat mesenteric resistance arteries.

BACKGROUND AND PURPOSE: ZP120 (Ac-RYYRWKKKKKKK-NH(2)), is a new partial nociceptin/orphanin FQ (NOP) receptor agonist with sodium-potassium sparing aquaretic effects. The mechanisms of vasodilatation of ZP120 were examined in rat mesenteric resistance arteries. EXPERIMENTAL APPROACH: Arterial segments (internal diameters 206+/-4 microm, n=224) were mounted in microvascular myographs for isometric tension recordings and electrical field stimulation (EFS). KEY RESULTS: ZP120 and the endogenous NOP receptor ligand, N/OFQ, did not relax arteries contracted with noradrenaline or adenosine-triphosphate. EFS-evoked contractions were inhibited by a purinoceptor antagonist, suramin, and the alpha(1)-adrenoceptor antagonist prazosin. N/OFQ inhibited, concentration-dependently, EFS-evoked contractions with a maximal effect of 52+/-3% (n=8) at 1 microM. The maximal effect of 1 microM ZP120 was lower (27+/-5%, P<0.05, n=9) than for N/OFQ. Endothelial removal or pretreatment with capsaicin did not influence the vasodilator effects of ZP120 and N/OFQ. ZP120 and N/OFQ responses were preserved in the presence of suramin. The alpha(2)-adrenoceptor antagonist, rauwolscine, antagonized the effect of clonidine and brimonidine, but ZP120 and N/OFQ inhibition of EFS-evoked contraction was unaltered. The competitive NOP receptor antagonist, UFP-101 (10 microM), prevented the inhibitory effect of N/OFQ, but not ZP120 suggesting that N/OFQ and ZP120 have distinct modes of interaction with the NOP receptor. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that the vasodilator effect of ZP120 and N/OFQ in rat mesenteric resistance arteries is mediated by prejunctional inhibition of adrenergic neurotransmission. These properties, that promote diuresis and attenuate the cardiovascular consequences of increased sympathetic nerve activity, make ZP120 a promising drug candidate.

The cholera toxin B subunit directly costimulates antigen-primed CD4+ T cells ex vivo.

The nontoxic B subunit of cholera toxin (CTB) has been used as an adjuvant in experimental systems of mucosal vaccination. However, the mechanisms behind its adjuvant effects remain unclear. Here, we have used an ex vivo system to elucidate these mechanisms in antigen-specific T cells. Using splenocytes from keyhole limpet haemocyanin (KLH)-immunized mice, initial experiments showed that recombinant CTB (rCTB) did not affect the KLH-specific proliferation of splenocytes isolated from mice immunized 2 weeks earlier. However, rCTB strongly enhanced the KLH-specific proliferation of splenocytes from mice immunized with KLH 4 weeks prior. This adjuvant effect was dose-dependent, with maximum at 30-300 ng/ml rCTB. At higher doses of CTB this effect declined because of the induction of apoptosis. Using antibody depletion and coculture systems, we show that rCTB directly costimulates KLH-specific CD4+ and CD8+ T-cell proliferation but not B cells. Enzyme-linked immunospot (ELISPOT) assays revealed that rCTB also enhanced the KLH-specific CD4+ T-cell-mediated production of interleukin-2 (IL-2), IL-4 and interferon-gamma(IFN-gamma) by four to fivefold. Characterizing the adjuvant effect of rCTB in vivo confirmed the results above, i.e. rCTB mediated a twofold increase in the ex vivo T-cell response when used as a classical adjuvant in a secondary, but not in a primary KLH-immunization regimen. Together these data show that rCTB can act as a strong adjuvant, by directly costimulating antigen-primed CD4+ and CD8+ T cell in a dose-dependent manner. This new insight might be valuable in the future rational design of bacterial toxin-based vaccines.

Coupling of oral human or porcine insulin to the B subunit of cholera toxin (CTB) overcomes critical antigenic differences for prevention of type I diabetes.

Our earlier investigations have demonstrated a critical difference in the efficacy of orally administered porcine compared to human or mouse insulin (no effect) in preventing type I diabetes in two distinct experimental models. Based on these findings one has to assume that certain insulins might not be suitable for the induction of oral 'tolerance'/bystander suppression, which might be one cause for recent failures in human oral antigen trials. Here we demonstrate that coupling to the non-toxic subunit of cholera toxin (CTB) can abolish these differences in efficacy between human and porcine insulin. As expected, an added benefit was the much smaller oral antigen dose required to induce CD4+ insulin-B specific regulatory cells that bystander-suppress autoaggressive responses. Mechanistically we found that uptake or transport of insulin-CTB conjugates in the gut occurs at least partially via binding to GM-1, which would explain the enhanced clinical efficacy. Both B chains bound well to major histocompatibility complex (MHC) class II, indicating comparable immunological potential once uptake and processing has occurred. Thus, our findings delineate a pathway to overcome issues in oral antigen choice for prevention of type I diabetes.

The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes.

When conjugated to various proteins, the nontoxic B-chain of cholera toxin (CTB) significantly increases the ability of these proteins to induce immunological tolerance after oral administration. Here, we investigated if a nonconjugated form of CTB enhances the induction of immune tolerance after oral insulin administration. Induction of immunological tolerance was studied after oral administration of insulin preparations in three mouse models; an insulin/ovalbumin coimmunization model, a model of virus-induced diabetes in transgenic RIP-LCMV-NP mice and in nonobese diabetic (NOD) mice serving as a model of spontaneous diabetes. In the immunization model, we demonstrate that mixing with CTB increases the tolerogenic potential of insulin, approximately 10 fold. Titration of the CTB concentration in this system revealed that an insulin : CTB ratio of 100 : 1 was optimal for the induction of bystander suppression. Further studies revealed that this insulin : CTB ratio also was optimal for the prevention of diabetes in a virus-induced, transgenic diabetes model. In addition, the administration of this optimal insulin-CTB preparation significantly prevented the onset of diabetes in old NOD mice with established islet infiltration. The data presented here demonstrate that CTB, even in its unconjugated form, functions as a mucosal adjuvant, increasing the specific tolerogenic effect of oral insulin.

Intracerebroventricular metformin attenuates salt-induced hypertension in spontaneously hypertensive rats.

The aim of this study was to examine the effects of long-term continuous intracerebroventricular (icv) infusion of metformin on blood pressure (BP) in spontaneously hypertensive rats (SHR). To accelerate the development of hypertension, SHR were fed a 8% NaCl diet during the 3-week study period. Metformin was given in the following doses: 0 (isotonic saline; n = 7), 25 (n = 8), 50 (n = 6), 100 (n = 6), and 200 microg/day icv (n = 5). Mean arterial pressure (MAP) and heart rate (HR) were measured by radiotelemetry, and as a measure of the contribution of sympathetic nerve activity to BP, the decrease in MAP in response to ganglionic blockade with hexamethonium, 30 mg/kg iv, was determined once weekly. In vehicle treated rats, MAP increased by 27+/-4 mm Hg, whereas in rats treated with a low dose of metformin (25 microg/day), MAP increased only by 7+/-3 mm Hg (P < .01). The hypotensive response to hexamethonium was attenuated by all doses of metformin suggesting that chronic icv metformin decreased central sympathetic outflow. The highest doses of metformin (100 and 200 microg/day) also prevented development of hypertension, but these doses were highly neurotoxic as demonstrated by histologic evaluation post mortem. Fast-Fourier transformation of MAP revealed increased variability within the 0.15 to 0.6 Hz frequency range in rats treated with neurotoxic doses of metformin, suggesting impaired sympathetic control of BP in these animals. In conclusion, long-term icv infusion with apparently nontoxic doses of metformin attenuates hypertension and decreases the hypotensive responses to ganglionic blockade in SHR, suggesting a centrally elicited sympathoinhibitory action.

Low prevalence of GAD and IA2 antibodies in schoolchildren from a village in the southwestern section of the Netherlands.

Glutamic acid decarboxylase (GAD) and insulinoma antigen 2 (IA2) antibodies are increasingly used as a tool to predict type I diabetes in children and as a differential diagnostic tool to distinguish type I and type II diabetes in adults. However, the background frequency of these antibodies in the general population has not been extensively studied and may differ between countries. The current study aims to establish the frequency of GAD and IA2 antibodies in an unselected population of schoolchildren and confirm the previously reported low prevalence of islet cell antibodies (ICA) in the general Dutch population. The study population consisted of 1403 unselected schoolchildren. All children were tested for GAD antibodies, and 1085 children were analyzed for IA2 antibodies by radiobinding assay. Development of diabetes was recorded during a 7-year follow-up. Five children (0.4%) were positive for GAD antibodies, one child (0.1%) was positive for IA2 antibodies. Two children developed diabetes during follow-up, one was positive for GAD antibodies only, the second was positive for both GAD and IA2 antibodies. The frequency of GAD and IA2 antibodies in the southwestern part of The Netherlands is low. This observation is in concordance with earlier studies on ICA in Dutch schoolchildren. For future diabetes prediction and intervention trials it is important to establish the background frequencies and predictive power of antibody screening in different populations.

Brain angiotensin receptors and sympathoadrenal regulation during insulin-induced hypoglycemia.

Simultaneous blockade of systemic AT1 and AT2 receptors or converting enzyme inhibition (CEI) attenuates the hypoglycemia-induced reflex increase of epinephrine (Epi). To examine the role of brain AT1 and AT2 receptors in the reflex regulation of Epi release, we measured catecholamines, hemodynamics, and renin during insulin-induced hypoglycemia in conscious rats pretreated intracerebroventricularly with losartan, PD-123319, losartan and PD-123319, or vehicle. Epi and norepinephrine (NE) increased 60-and 3-fold, respectively. However, the gain of the reflex increase in plasma Epi (Deltaplasma Epi/Deltaplasma glucose) and the overall Epi and NE responses were similar in all groups. The ensuing blood pressure response was similar between groups, but the corresponding bradycardia was augmented after PD-123319 (P < 0.05 vs. vehicle) or combined losartan and PD-123319 (P < 0.01 vs. vehicle). The findings indicate 1) brain angiotensin receptors are not essential for the reflex regulation of Epi release during hypoglycemia and 2) the gain of baroreceptor-mediated bradycardia is increased by blockade of brain AT2 receptors in this model.

Muscle glycogen stores and meat quality as affected by strategic finishing feeding of slaughter pigs.

The aim of the present study was to investigate whether muscle glycogen stores in slaughter pigs could be decreased through strategic finishing feeding before slaughter. Moreover, preliminary meat quality traits were measured to see whether such a regulation of muscle glycogen stores affected ultimate pH, color, and tenderness in the meat. The strategic finishing feeding was carried out the last 3 wk prior to slaughter. Seven experimental groups with eight animals per group were fed diets low in digestible carbohydrates. A control group with four animals was fed a traditional grower-finishing diet. The muscle glycogen stores were reduced in longissimus muscle (LM) 11 to 26% at the time of slaughter in pigs that were fed the experimental diets compared with the control group. Meat quality measured as ultimate pH and color on LM muscle in half the pigs 24 h postmortem showed that ultimate pH in LM was not affected by the reduction in glycogen stores in the muscles from pigs fed any of the experimental diets. However, the meat from pigs fed the experimental diets was darker than the meat from pigs that were fed the control diet with two of the experimental diets, resulting in significantly lower L* values. Activities of key enzymes in the glycolytic pathway, glycogen phoshorylase a and b, phosphofructokinase, and the fatty acid oxidative pathway, beta-hydrozyacyl-CoA-dehydrogenase, were not affected by the strategic feeding. In contrast, the activity of the proteolytic enzyme calpain as well as its inhibitor calpastatin was influenced by the strategic feeding. Lower activity of mu-calpain and greater activity of calpastatin in the muscle samples from the strategically fed pigs indicate a lesser muscle protein degradation in the muscles compared with muscles of control animals. The present study showed that the muscle glycogen stores in slaughter pigs can be reduced at the time of slaughter through strategic finishing feeding with diets low in digestible carbohydrate without compromising growth rate.

Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis.

The authors examined the natriuretic efficiency of furosemide in rats with cirrhosis induced by carbon tetrachloride (CCl(4)). Rats were treated for 17 weeks with intraperitoneal injections of CCl(4) in groundnut oil twice a week throughout the study. Control rats were treated with vehicle (groundnut oil). Studies in metabolic cages showed that sodium retention was present from week 14. Renal clearance experiments were performed in chronically, instrumented conscious rats at the end of week 14 and at the termination of the study (end week 16) when ascites and hyponatremia were present. After 14 weeks, cirrhotic rats had sodium retention along with increased renal plasma flow, normal GFR, normal renal lithium handling, and a significantly increased diuretic (+41% vs. control) and natriuretic (+56% vs. control) response to a test dose furosemide (7.5 mg/kg b.w., intravenously). The natriuretic efficiency of furosemide, i.e., the natriuresis expressed relative to the furosemide excretion rate (triangle upU(Na)V/U(FUR)V) was increased by 51% versus control. After 17 weeks, ascites and hyponatremia had developed, and significant decreases in renal plasma flow (-33%), GFR (-30%), and fractional lithium excretion (-44%) were observed. At this stage urinary recovery of furosemide was significantly decreased and the diuretic (-27% vs. Control) and natriuretic (-38% vs. control) responses to furosemide were significantly impaired. However, the increased natriuretic efficiency of furosemide was still present (+34% vs. control). Together these results suggest that increased sodium reabsorption in the thick ascending limb of Henle's loop is involved in the renal sodium retention in cirrhosis in rats that eventually results in decompensation with the formation of ascites.

Decreased vasopressin-mediated renal water reabsorption in rats with chronic aldosterone-receptor blockade.

Previous studies have suggested that mineralocorticoids are needed for a normal action of vasopressin on collecting duct osmotic water permeability. However, the mechanisms behind this are unknown. To investigate if aldosterone-receptor blockade influences vasopressin type 2 receptor (V(2))-mediated renal water reabsorption and the renal expression of the vasopressin-regulated water channel aquaporin-2 (AQP2), rats were treated with the aldosterone-receptor antagonist canrenoate (20 mg/day iv) for 4 wk. Daily urine flow was increased significantly by 44%, and urine osmolality was decreased by 27% in canrenoate-treated rats. Acute V(2)-receptor blockade (OPC-31260, 800 microgram. kg(-1). h(-1)) was performed under conditions in which volume depletion was prevented. In control rats, OPC-31260 induced a significant increase in urine flow rate (V, +25%) and free water clearance (C(H(2)O), -29%). In canrenoate-treated rats, the effect of OPC-31260 was significantly reduced, and semiquantiative immunoblotting demonstrated a significant reduction (45%) in AQP2 expression. Because rats with common bile duct ligation (CBL) have a reduced vasopressin-mediated water reabsorption compared with normal rats (V: -24%; C(H(2)O): -28%, and 86% downregulation of AQP2), the effect of canrenoate combined with OPC-31260 was tested. Canrenoate treatment of CBL rats significantly increased daily urine flow, decreased urine osmolality, and impaired the aquaretic response to OPC-31260 (V: -23%; C(H(2)O): -31%) with maintained suppression of the renal AQP2 expression. Thus canrenoate treatment of normal and CBL rats showed 1) increased urine production, 2) reduced aquaretic effect of acute V(2)-receptor blockade, and 3) a marked reduction in AQP2 expression. This strongly supports the view that aldosterone plays a significant role for vasopressin-mediated water reabsorption.

Relationship between RN(-) genotype and drip loss in meat from Danish pigs.

The presence of the RN(-)-gene determined in 72 halothane negative Danish pigs, either by a direct genotyping or the glycolytic potential of the meat, in relation to drip loss, was investigated. The drip loss in the M. longissimus dorsi from RN-carriers (n=26), as determined by genotyping was 9.9% compared to 8.6% in non-carriers (n=46) (P=0.07). When a glycolytic potential of >230 µmol lactate/g meat was used to differentiate between carriers and non carriers of the RN(-)-gene, the drip loss in carriers was 10.6% (n=17) compared to 8.7% in non-carriers (n=55) (P<0.01). These results suggest that the presence of the RN(-)-gene in Danish slaughter pigs only partially explains the large variation in drip loss observed in Danish pork.

Albuminuria in ischemic heart disease.

Proteinuria associated with acute heart disease was studied prospectively in 160 patients admitted to the coronary care unit with suspected AMI. Series 1 comprised 150 patients, divided into the following groups: AMI, 27 UAP, 43 AP, 22 NIP and 18 excluded. Albumin and creatinine were measured in the first urine passed after admission (sample 1) and the first morning urine the following 2 days (samples 2 and 3). The ACR was significantly higher in the AMI and UAP groups than in the other patient groups (p < 0.0001). There was no significant difference of ACR between the AMI and UAP in sample 1 (p = 0.31). In the AMI, UAP and AP groups ACR was significantly higher in sample 1 than in samples 2 and 3 (p < 0.005). In the NIP group there were no significant differences between sample 1 versus samples 2 and 3 (p = 0.06). Series 2 comprised 10 patients: 8 AMI, 1 UAP and 1 AMYO. ACR were measured in all specimens voided during the period of observation. ACR can oscillate within hours between normal concentrations and concentrations well into or above the microalbuminuric range. We propose the term episodic albuminuria for this reversible, switch-like change in renal function. The albuminuric episodes lasted 90-600 minutes. Maximum values for ACR were between 133-790 mumol/mol or 78-466 mg/g. In healthy, resting individuals ACR is < 50 mumol/mol (< 30 mg/g). The rapid changes in glomerular permeability may reflect systemic changes in endothelial permeability in the affected individuals. We speculate that atrial natriuretic peptide (ANP) may be a mediator of this type of albuminuria.