Telling the same story: Fishers and landing data reveal changes in fisheries on the Southeastern Brazilian Coast.

An understanding of the effects of fishing on marine ecosystems relies on information about the conserved state of these environments. Non-conventional approaches such as the use of historical data and local ecological knowledge can provide information and help adjust our references of changes in the environment. Also, the combination of different types of data can indicate a fisheries trend that would be undetectable when evaluated separately. Here we investigated changes in fisher's perceptions regarding overexploited and new target species in artisanal fisheries in a secular fishing village of the subtropical, southeastern Brazilian coast. We identified temporal changes in landings and in the mean trophic level (MTL) of high trophic level species (≥ 3.5 and >4) over 16 years. Fishers' knowledge revealed shifts in perception associated with years of fishing practice. More experienced fishers recognized a greater number of overexploited and new target species than fishers in the beginning of their careers. Landing data has revealed declining trends of 72% for five mesopredators species. Due to the overfishing of mesopredators, there was a shift in target species, towards fish that were previously discarded. Temporal changes in landings and in the MTL metric are concordant with previous reports on the overexploitation of species caught by local fishers. Our work reveals that multiple sources of information can be combined to establish historical baselines and improve the detection of change in marine ecosystems.

Does the colors of light matter? Testing different light color in nocturnal underwater visual censuses.

Most methods for assessing reef fish assemblages at night require artificial light, but the use of different colors of light may influence the results. We used data from 135 underwater visual censuses (UVCs) performed with different colors of light (red, blue and white) to evaluate the structure of fish assemblages on subtropical rocky reefs along three depth intervals. We did not detect any effect of the color of light on total density or fish species richness per transect, nor on the structure of the entire assemblage. However, the density of some of the most abundant species varied according to the color used. Red light showed the highest values of frequency of occurrence for most species, while the white light resulted in decreased abundance of some fish species. Our results emphasize the importance of choosing the color of light depending on the type of studies to be conducted. This will depend on the objectives of the research (e.g. inventory, behavior or community dynamics) and the target fish fauna (e.g. mobile or sedentary).

Decline in abundance and health state of an Atlantic subtropical gorgonian population.

Losses in coral cover have been widely reported for the Caribbean. In contrast, much less is known about the health state of the Brazilian reef fauna, which was declared as a priority for Atlantic biodiversity conservation due to its high degree of endemism. In the present study, we assessed the general health state of Phyllogorgia dilatata assemblages at the subtropical reefs of Arraial do Cabo (southeastern Brazil), where observations suggest that the abundance of this endemic gorgonian species has declined. We found that about 49% of the sampled colonies were dead, and 73% of the living colonies were affected by tissue loss. Tissue loss initially manifested as multifocal holes in the planar colonial coenenchyme and peripheral tissue retraction leaving denuded skeletal axes. In combination with other recent studies, our results raise the awareness for an increasingly threatened Southwestern Atlantic reef coral fauna.

First Record of Invasive Lionfish (Pterois volitans) for the Brazilian Coast.

The invasion of the northwestern Atlantic by the Indo-Pacific lionfish has developed extraordinarily fast, and is expected to cause one of the most negative ecological impacts among all marine invasions. In less than 30 years, lionfish have dramatically expanded their distribution range to an area encompassing the eastern coast of the USA, Bermuda, the entire Caribbean region and the Gulf of Mexico. The rapidity of the lionfish spread has raised concerns in other parts of the Atlantic that may be under the reach of the invasion. Despite the anticipation that lionfish would eventually extend their range throughout most of the eastern coast of South America, it had not been recorded in Brazil until now. Here we report the first lionfish appearance for the Brazilian coast and show that the individual collected by us is genetically linked to the invasive Caribbean population. Since small-range endemics are found in several locations in Brazil and are among the species that are most vulnerable to extinction, we recommend urgent control, management and education measures aimed at minimizing the effects of this impending invasion.

Independent fusions and recent origins of sex chromosomes in the evolution and diversification of glass knife fishes (Eigenmannia).

The genus Eigenmannia comprises several species groups that display a surprising variety of diploid chromosome numbers and sex-determining systems. In this study, hypotheses regarding phylogenetic relationships and karyotype evolution were investigated using a combination of molecular and cytogenetic methods. Phylogenetic relationships were analyzed for 11 cytotypes based on sequences from five mitochondrial DNA regions. Parsimony-based character mapping of sex chromosomes confirms previous suggestions of multiple origins of sex chromosomes. Molecular cytogenetic analyses involved chromosome painting using probes derived from whole sex chromosomes from two taxa that were hybridized to metaphases of their respective sister cytotypes. These analyses showed that a multiple XY system evolved recently (<7 mya) by fusion. Furthermore, one of the chromosomes that fused to form the neo-Y chromosome is fused independently to another chromosome in the sister cytotype. This may constitute an efficient post-mating barrier and might imply a direct function of sex chromosomes in the speciation processes in Eigenmannia. The other chromosomal sex-determination system investigated is shown to have differentiated by an accumulation of heterochromatin on the X chromosome. This has occurred in the past 0.6 my, and is the most recent chromosomal sex-determining system described to date. These results show that the evolution of sex-determining systems can proceed very rapidly.

Simultaneous detection of the C282Y, H63D and S65C mutations in the hemochromatosis gene using quenched-FRET real-time PCR.

Hereditary hemochromatosis (HH) is a common autosomal disorder of iron metabolism mainly affecting Caucasian populations. Three recurrent disease-associated mutations have been detected in the hemochromatosis gene (HFE): C282Y, H63D, and S65C. Although HH phenotype has been associated with all three mutations, C282Y is considered the most relevant mutation responsible for hemochromatosis. Clinical complications of HH include cirrhosis of the liver, congestive cardiac failure and cardiac arrhythmias, endocrine pancreatic disease, which can be prevented by early diagnosis and treatment. Therefore, a reliable genotyping method is required for presymptomatic diagnosis. We describe the simultaneous detection of the C282Y, H63D and S65C mutations in the hemochromatosis gene by real-time PCR followed by melting curve analysis using fluorescence resonance energy transfer (FRET) probes. The acceptor fluorophore may be replaced by a quencher, increasing multiplex possibilities. Real-time PCR results were compared to the results of sequencing and conventional PCR followed by restriction digestion and detection by agarose gel electrophoresis (PCR-RFLP). Genotypes from 80 individuals obtained both by the conventional PCR-RFLP method and quenched-FRET real-time PCR were in full agreement. Sequencing also confirmed the results obtained by the new method, which proved to be an accurate, rapid and cost-effective diagnostic assay. Our findings demonstrate the usefulness of real-time PCR for the simultaneous detection of mutations in the HFE gene, which allows a reduction of a significant amount of time in sample processing compared to the PCR-RFLP method, eliminates the use of toxic reagents, reduces the risk of contamination in the laboratory, and enables full process automation.

Simultaneous detection of the C282Y, H63D and S65C mutations in the hemochromatosis gene using quenched-FRET real-time PCR

Hereditary hemochromatosis (HH) is a common autosomal disorder of iron metabolism mainly affecting Caucasian populations. Three recurrent disease-associated mutations have been detected in the hemochromatosis gene (HFE): C282Y, H63D, and S65C. Although HH phenotype has been associated with all three mutations, C282Y is considered the most relevant mutation responsible for hemochromatosis. Clinical complications of HH include cirrhosis of the liver, congestive cardiac failure and cardiac arrhythmias, endocrine pancreatic disease, which can be prevented by early diagnosis and treatment. Therefore, a reliable genotyping method is required for presymptomatic diagnosis. We describe the simultaneous detection of the C282Y, H63D and S65C mutations in the hemochromatosis gene by real-time PCR followed by melting curve analysis using fluorescence resonance energy transfer (FRET) probes. The acceptor fluorophore may be replaced by a quencher, increasing multiplex possibilities. Real-time PCR results were compared to the results of sequencing and conventional PCR followed by restriction digestion and detection by agarose gel electrophoresis (PCR-RFLP). Genotypes from 80 individuals obtained both by the conventional PCR-RFLP method and quenched-FRET real-time PCR were in full agreement. Sequencing also confirmed the results obtained by the new method, which proved to be an accurate, rapid and cost-effective diagnostic assay. Our findings demonstrate the usefulness of real-time PCR for the simultaneous detection of mutations in the HFE gene, which allows a reduction of a significant amount of time in sample processing compared to the PCR-RFLP method, eliminates the use of toxic reagents, reduces the risk of contamination in the laboratory, and enables full process automation.

Chromosome evolution in fish: sex chromosome variability in Eigenmannia virescens (Gymnotiformes: Sternopygidae).

New data are presented on the sex chromosomes of the fish species Eigenmannia virescens (Gymnotiformes, Sternopygidae). A new finding, involving the occurrence of ZZ/ZW sex chromosomes, is described in specimens sampled from the São Francisco and Amazon river basins in Brazil. All individuals had a chromosome number of 2n = 38. The homologs of the sex chromosome pair from the São Francisco river basin sample differed only in their morphology, while those from the Amazonian sample differed both in morphology and heterochromatin pattern. A possible model for the evolution of the sex chromosomes in E. virescens is proposed, including data from populations from the Paraná (Brazil) river basin, in which male heterogamety has already been described. The occurrence of different sex chromosome systems in species and populations of the neotropical freshwater fish fauna is discussed.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver.

PURPOSE: Although oral fluoropyrimidine prodrugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. METHOD: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m2) OGT 719. RESULTS: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. CONCLUSION: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Inhibition of substrate synthesis as a strategy for glycolipid lysosomal storage disease therapy.

The glycosphingolipid (GSL) lysosomal storage diseases are caused by mutations in the genes encoding the glycohydrolases that catabolize GSLs within lysosomes. In these diseases the substrate for the defective enzyme accumulates in the lysosome and the stored GSL leads to cellular dysfunction and disease. The diseases frequently have a progressive neurodegenerative course. The therapeutic options for treating these diseases are relatively limited, and for the majority there are no effective therapies. The problem is further compounded by difficulties in delivering therapeutic agents to the brain. Most research effort to date has focused on strategies for augmenting enzyme levels to compensate for the underlying defect. These include bone marrow transplantation (BMT), enzyme replacement and gene therapy. An alternative strategy that we have been exploring is substrate deprivation. This approach aims to balance the rate of GSL synthesis with the impaired rate of GSL breakdown. The imino sugar N-butyldeoxynojirimycin (NB-DNJ) inhibits the first step in GSL biosynthesis and has been used to evaluate this approach. Studies in an asymptomatic mouse model of Tay-Sachs disease have shown that substrate deprivation prevents GSL storage in the CNS. In a severe neurodegenerative mouse model of Sandhoff disease, substrate deprivation delayed the onset of symptoms and disease progression and significantly increased life expectancy. Combining NB-DNJ and BMT was found to be synergistic in the Sandhoff mouse model. A clinical trial in type I Gaucher disease has been undertaken and has shown beneficial effects. Efficacy was demonstrated on the basis of significant decreases in liver and spleen volumes, gradual but significant improvement in haematological parameters and disease activity markers, together with diminished GSL biosynthesis and storage as determined by independent biochemical assays. Further trials in type I Gaucher disease are in progress; studies are planned in patients with GSL storage in the CNS.

Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis.

BACKGROUND: Current treatment for Gaucher's disease involves administration of intravenous glucocerebrosidase to degrade glucocerebroside stored in lysosomes. Lowering the rate of biosynthesis of glucocerebroside should decrease accumulation of this substrate. We investigated the safety and efficacy of OGT 918 (N-butyldeoxynojirimycin), an inhibitor of glucosyltransferase, as a novel oral treatment for non-neuronopathic Gaucher's disease. METHODS: We recruited, into a 1-year open-label study, 28 adults (seven with previous splenectomies) from four national Gaucher's referral clinics, who were unable or unwilling to receive enzyme treatment. We measured liver and spleen volume by computed tomography or magnetic resonance imaging at baseline and at months 6 and 12, and biochemical and haematological variables monthly, including chitotriosidase activity (a sensitive marker of Gaucher's disease activity). Patients were started on 100 mg oral OGT 918 three times daily. FINDINGS: Baseline liver volumes were 1.1-2.7 times normal and spleen volumes 5.1-24.8 times normal. At 12 months, mean liver and spleen volumes were significantly lowered by 12% (95% CI 7.8-16.4) and 19% (14.3-23.7), respectively (each p<0.001). Haematological variables improved slightly. Mean organ volume and blood counts improved continually between 6 months and 12 months of treatment. Mean chitotriosidase concentrations fell by 16.4% over 12 months (p<.0001). Six patients withdrew because of gastrointestinal complaints (two), personal reasons (two), or severe pre-existing disease (two). The most frequent adverse effect was diarrhoea, which occurred in 79% of patients shortly after the start of treatment. INTERPRETATION: Decrease of substrate formation by OGT 918 improves key clinical features of non-neuronopathic Gaucher's disease. The strategy justifies further trials in this and other glycosphingolipid storage disorders.

The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus.

To explore further the effects of the human amylin analog pramlintide on overall glycemic control and postprandial responses of circulating glucose, glucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male type 1 diabetic patients were examined in a double-blind, placebo-controlled, crossover study. Pramlintide (30 microg four times daily) or placebo were administered for 4 weeks, after which a daytime blood profile (8:30 AM to 4:30 PM) was performed. Serum fructosamine was decreased after pramlintide (314+/-14 micromol/L) compared with placebo (350+/-14 micromol/L, P = .008). On the profile day, the mean plasma glucose (8.3+/-0.7 v 10.2+/-0.8 mmol/L, P = .04) and postprandial concentrations (incremental areas under the curve [AUCs] from 0 to 120 minutes) were significantly decreased during pramlintide administration (P < .01 for both) despite comparable circulating insulin levels (359+/-41 v 340+/-35 pmol/L). Mean blood glycerol values were reduced (0.029+/-0.004 v 0.040+/-0.004 mmol/L, P = .01) and blood alanine levels were elevated (0.274+/-0.012 v 0.246+/-0.008 mmol/L, P = .03) after pramlintide versus placebo. Blood lactate concentrations did not differ during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished (P = .02), and a similar trend was observed following lunch. In addition, peak plasma glucagon concentrations 60 minutes after breakfast (45.8+/-7.3 v 72.4+/-8.0 ng/L, P = .005) and lunch (47.6+/-9.0 v 60.9+/-8.2 ng/L, P = .02) were both decreased following pramlintide. These data indicate that pramlintide (30 microg four times daily) is capable of improving metabolic control in type 1 diabetics. This may relate, in part, to suppression of glucagon concentrations. Longer-term studies are required to ascertain whether these findings are sustained over time.

Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM.

Pramlintide, a human amylin analogue, reduces hyperglycaemia after meals in patients with insulin-dependent diabetes mellitus (IDDM). We investigated whether this was due to delayed gastric emptying. Eight men with uncomplicated IDDM were studied twice in a randomised, double-blind crossover design. Euglycaemia was maintained overnight by intravenous infusion of glucose and/or insulin and the following morning a 5-h infusion of pramlintide 25 micrograms/h or placebo was started at 08.00 hours. At 08.30 hours the patients injected their normal morning insulin dose subcutaneously and 30 min later ate a meal (600 kcal, 50% carbohydrate) of which the solid component was labelled with Technetium-99 m and the liquid with Indium-111 to quantify gastric emptying. Gamma-scintigraphic images were obtained every 20 min for the next 4 h. Insulin and glucose were infused as necessary to maintain blood glucose levels within 3 mmol/l of the pre-meal value. Compared to placebo, pramlintide significantly delayed emptying of both liquid (median lag time 69 vs 7.5 min) and solid (median lag time 150 vs 44.5 min) components of the meal. Pramlintide delayed gastric emptying so much that t50 values could not be calculated for solid or liquid. Amylin agonists such as pramlintide may, therefore, be of value in improving glycaemic control in IDDM by modifying gastric emptying.

Modulation of gastric emptying as a therapeutic approach to glycaemic control.

Amylin is a peptide hormone which is deficient in patients with Type 1 and late stage Type 2 diabetes. Evidence from studies in rats and humans has suggested that it is involved in glucose homeostasis by modulating gastric emptying and, possibly, by regulating the release of glucagon. These observations have led to the suggestion that amylin may be used clinically to improve glycaemic control in patients with diabetes. Preliminary studies with the human amylin analogue, pramlintide, have provided evidence of beneficial effects in terms of improved glycaemic control in these patients; these effects are currently being investigated in long term phase III studies.

Acute effects of the human amylin analog AC137 on basal and insulin-stimulated euglycemic and hypoglycemic fuel metabolism in patients with insulin-dependent diabetes mellitus.

Amylin has been reported to decrease glycogen storage in rodent skeletal muscles and produce insulin resistance in intact rats. To test the acute effect of a human amylin analog (AC137) on glucose metabolism in man, seven IDDM patients were infused in a randomized, double blind, cross-over study with AC137 (100 micrograms/h, n = 1; 50 micrograms/h, n = 6) or placebo for 330 min during a two-step euglycemic clamp (insulin infusion rates, 0.2 and 0.6 mU/kg.min; basal and hyperinsulinemic period, respectively) followed by a hyperinsulinemic hypoglycemic clamp (insulin infusion rate, 1.5 mU/kg.min; hypoglycemic period). During euglycemia, no differences were found in glucose disposal (step 1, 2.43 +/- 0.20 vs. 2.03 +/- 0.26; step 2, 4.28 +/- 0.54 vs. 4.11 +/- 0.45 mg/kg.min; AC137 vs. placebo, mean +/- SEM), arteriovenous substrate balances across the forearm, or hepatic glucose production. During hypoglycemia, glucose fluxes were also similar. However, lactate release from the forearm was more pronounced (P < 0.05) with the analog than with placebo (area under the curve, -11.2 +/- 4.6 vs. -1.4 +/- 2.2 mmol/min.L). Despite similar plasma glucose nadirs (2.7 +/- 0.0 vs. 2.6 +/- 0.1 mmol/L; AC137 vs. placebo), circulating cortisol and GH rose to significantly higher levels during hypoglycemia with the amylin analog (P < 0.05). In conclusion, acute administration of the amylin analog AC137 did not influence insulin-stimulated glucose metabolism during euglycemic conditions. During imposed hypoglycemia, lactate release from skeletal muscle was, however, enhanced, and the rise in cortisol and GH was augmented.

Reduction of postprandial hyperglycemia in subjects with IDDM by intravenous infusion of AC137, a human amylin analogue.

OBJECTIVE: To demonstrate that intravenous administration of AC137 (25,28,29 tripro-human amylin), a human amylin analogue, modulates the rate of appearance of glucose derived from a standard oral meal in the peripheral circulation of patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: After the observation that a 2-h infusion of AC137 at a rate of 150 micrograms/h, in conjunction with the subjects' usual morning insulin dose, decreased postprandial hyperglycemia in 6 subjects with IDDM, a double-blind placebo-controlled two-period crossover design in an additional 18 IDDM patients was undertaken to confirm and extend the observation. Based on reasoning that an effect to modulate the appearance of orally administered glucose would have no impact on the disposition of an intravenous glucose load, nine patients were challenged with an intravenous glucose loads (300 mg/kg), while another nine patients were challenged with a standardized Sustacal meal (350 kcal) during a 5-h infusion of AC137 (50 micrograms/h). On each occasion, the subjects received their usual morning doses of insulin subcutaneously. The impact of the AC137 infusion on the plasma glucose responses to these different challenges was assessed. RESULTS: Intravenous infusion of AC137 yielding steady state plasma concentrations of 225 +/- 15 pmol/l (mean +/- SE) reduced postprandial plasma glucose concentrations after the standardized Sustacal meal challenge. The mean area under the glucose curve, corrected for baseline, was reduced from -1,869 +/- 5,562 mg.dl-1.min during placebo infusion to -28,872 +/- 4,812 mg.dl-1.min during AC137 infusion, P = 0.0015. In contrast, an AC137 infusion producing steady-state concentrations of 234 +/- 16 pmol/l had no effect on the plasma glucose profile after administration of an intravenous glucose load. CONCLUSIONS: AC137 administration, in these patients with IDDM, reduced postprandial hyperglycemia apparently by affecting the delivery rate of glucose from the gastrointestinal tract. AC137 may prove to be a clinically useful addition to insulin regimens to facilitate the achievement of glycemic control.

Safety of long-term use of lisinopril for congestive heart failure.

Early clinical experience with lisinopril suggested that it was well tolerated in congestive heart failure (CHF). An analysis of data from greater than 1,000 patients treated with lisinopril has been performed to examine the long-term safety of lisinopril in CHF. Of these, 620 have been studied for up to nearly 4 years, and a further 440 have been studied in comparative trials for 3 months. When patients who received lisinopril or placebo for the same period were compared, the proportion of lisinopril patients reporting an adverse event was 44.1% compared with 39.4% on placebo. Over a 4-year period, 205 patients (33.1%) discontinued treatment. About 33% of these died, 33% withdrew due to clinical adverse events, 21 (3.4%) were withdrawn because of adverse laboratory findings, and 56 (9.0%) withdrew for reasons unrelated to treatment. Sixteen patients (2.6%) withdrew because lisinopril was deemed ineffective. The most frequently reported drug-related adverse laboratory findings were increases in blood urea nitrogen, blood urea, serum creatinine, and plasma potassium. There appeared to be no differences in the pattern of adverse events with respect to the race of the patient. Elderly patients and those with the most severe forms of heart failure appeared to be at greater risk for an adverse event. Evaluation of the safety of lisinopril compared with enalapril, captopril, and digoxin in controlled clinical trials shows all the angiotensin-converting enzyme inhibitors to be equally well tolerated with a closely similar range of adverse events, suggesting that the satisfactory safety profile of lisinopril is shared by other drugs of this class.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of ANF 99-126 and ANF 103-126 on captopril-induced renin release in man.

OBJECTIVE: The aim was to examine the effects of atrial natriuretic factor (ANF) 99-126 and ANF 103-126, an N-terminal shortened analogue of the peptide, on the plasma renin activity response to captopril, an inhibitor of angiotensin-converting enzyme. DESIGN: Two protocols were performed. In the first protocol, subjects were studied on three occasions. Captopril 25 mg was given and a 60 minute infusion of 5% D-glucose (placebo), or ANF 99-126 3 or 10 pmol/kg/min, was administered in a single blind randomized manner. The second protocol was divided in two parallel phases comparing ANF 103-126 either 3 or 10 pmol/kg/min to placebo. SUBJECTS: Thirty-three salt-replete healthy male volunteers aged 21-39 years were studied in the supine position. MEASUREMENTS: Plasma renin activity, plasma ANF 99-126 and ANF 103-126 levels, heart rate and blood pressure were measured. RESULTS: Compared to placebo infusion, the rise in plasma renin activity after captopril was attenuated by ANF 99-126 infusion (from 755% of baseline to 294% by ANF 99-126 3 pmol/kg/min and from 755 to 202% by 10 pmol/kg/min; P less than 0.03 and P less than 0.01 respectively). The comparable findings with ANF 103-126 were 492 to 218% (3 pmol/kg/min) and 645 to 364% (10 pmol/kg/min) (P less than 0.01 and P less than 0.01 respectively). CONCLUSIONS: The results, taken in conjunction with previous findings, suggest that atrial natriuretic factor inhibits in a non-selective manner the renin response to all secretagogues so far tested in man. The current results also suggest that the anti-renin action of atrial natriuretic factor does not depend on the first four N-terminal amino acids of the native peptide.

Effect of intravenous infusion of atriopeptin 3 on immediate renal allograft function.

Thirty-eight recipients of nineteen pairs of cadaveric kidneys were entered into a double-blind randomized study in which one recipient received a 12-hour intravenous infusion of Atriopeptin III (AP-3), a synthetic analogue of atrial natriuretic factor, commencing at release of the vascular clamps, and the other received a placebo infusion. In an initial dose ranging study, successive groups of six kidneys (3 pairs) were randomized to receive each of 0.0125, 0.025, 0.05 micrograms/kg/min AP-3 or placebo. Thereafter 20 kidneys (10 pairs) received 0.1 micrograms/kg/min or placebo. There was no discernable effect of AP-3 on allograft creatinine clearance or sodium excretion either when the highest dose of AP-3 was considered alone or when all doses were considered together. Averaged creatinine clearance over the period 0 to 24 hours after transplantation was 20.1 +/- 14.7 ml/min in patients receiving active treatment and 18.2 +/- 13.7 ml/min in those receiving placebo. Thus, despite the documentation of a protective effect of atrial natriuretic factor in animal models of renal ischemia, it is unlikely that intravenous infusion of AP-3 in this dose range will be of benefit in improving immediate renal allograft graft function.

Haemoconcentration and accumulation of white cells in the feet during venous stasis.

In experiments on eight healthy human subjects changes in the composition of the venous blood leaving the foot were examined during a 45-min period of sitting. Each subject reclined for 30-min before sitting with the foot approximately 1 m below the heart. Fluid filtration from the plasma into the tissues during sitting raised the haematocrit from an initial value of 41 +/- 0.6% to 49 +/- 1% after 20-min and to 51 +/- 1.5% at 40-min. The corresponding increase in plasma protein concentration was from 6.5 +/- 0.1 gdl-1 to 8.0 +/- 0.2 gdl-1 after 20 min and to 9.0 +/- 0.3 gdl after 40-min of sitting. Plasminogen activator levels in the foot venous blood during sitting were raised two to three fold over those found in venous blood taken from the arm at the start of the experiment. By contrast, after 20 min of sitting, white cell count of the venous blood of the foot was unchanged from the initial value of 7.4 +/- 0.8 X 10(-9) l-1 and increased to only 7.8 +/- 0.9 X 10(-9) l-1 at 40-min. This was in spite of an increase in the number of circulating white cells which, in blood taken from the arm at 45-min, had risen to 8.3 +/- 0.8 X 10(-9) l-1. The venous blood leaving the feet also failed to show an increase in platelet numbers. It is argued that approximately 15-20% of the white cells entering the feet during quiet sitting, do not leave in the venous blood. The possible significance of the results to the pathophysiology of venous hypertension is discussed.