Urine methylhistamine concentrations before and after chloroquine in healthy black subjects

Urine concentrations of methylhistamine were measured in 11 subjects who experienced itching with chloroquine ('itchers') and in 14 who did not itch ('non-itchers'). In each group, urine methylhistamine concentrations were significantly greater at 12, 24 and 36 h after ingestion of 1 g chloroquine phosphate than before. There was no significant difference between itchers and non-itchers as regards urine methylhistamine concentrations at any time-point. Furthermore, there was no correlation between urine methylhistamine concentration and degree of pruritus in itchers. The findings suggest that histamine may be released by chloroquine, but it is unlikely to be the main cause of chloroquine-induced pruritus.     

Plasma concentrations of sulfadoxine in healthy and malaria infected Thai subjects

The disposition of sulfadoxine was studied in the presence of pyrimethamine in 18 healthy Thai subjects who had been suffering from falciparum malaria in the 6 months prior to the study, and in 12 Thai patients with acute malaria. The volunteers were administered an oral dose of 500 mg sulfadoxine + 25 mg pyrimethamine (1 Fansidar tablet). They were classified retrospectively as responders (Group I, n = 8) or nonresponders (Group II, n = 10) according to previous response to treatment with Fansidar. The patients were treated with 3 Fansidar tablets corresponding to 1500 mg sulfadoxine and 75 mg pyrimethamine. Five of them were completely cured. Seven patients showed R I or R II resistance. In all cases blood samples were collected up to 288 h post dose. The resultant plasma was analyzed for active (i.e. unchanged) and total sulfadoxine using a modified Bratton-Marshall method. In the healthy volunteers the plasma concentration time course of total sulfadoxine was similar for responding and nonresponding subjects. However, in nonresponders active sulfadoxine tended to show shorter half-lives (harmonic means were 212 h vs 267 h, respectively). Furthermore, significantly higher amounts of metabolites (mainly N4-acetylsulfadoxine) were present in plasma of nonresponders. In contrast to these findings, in malaria patients, plasma concentrations of active and total sulfadoxine were even higher in nonresponders as compared to the subjects who could be successfully cured. Furthermore, in this case there was no increase of the amount of metabolites in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma nitric oxide concentrations are elevated in insulin-resistant healthy subjects

The goal of this study was to compare plasma nitric oxide (NO) concentrations in healthy subjects, defined as either insulin-resistant or insulin-sensitive on the basis of the plasma insulin response to a 75-g oral glucose challenge. For this purpose, 404 healthy subjects were divided into quartiles on the basis of the plasma insulin response to glucose, and 49 individuals were selected from the quartile with the lowest insulin response and 49 from the quartile with the highest insulin response. The two groups of 49 each were selected to be essentially identical in terms of age, gender distribution, body mass index (BMI), and waist to hip ratio (WHR). The quartile with the greatest insulin response also had a significantly higher plasma glucose response to oral glucose, faster heart rate, higher blood pressure, and the combination of higher triglyceride and lower high-density lipoprotein (HDL) cholesterol concentrations. In addition to the latter changes, previously shown to be associated with hyperinsulinemia, NO concentrations were also higher in the hyperinsulinemic group. It is speculated that this increase in the NO concentration in hyperinsulinemic and presumably insulin-resistant, subjects represents a compensatory effort to overcome the untoward effects of insulin resistance and/or hyperinsulinemia.     

Comparison between serum interleukin-2 concentrations in healthy adult and elderly subjects

The serum interleukin-2 (IL-2) concentrations were evaluated in healthy elderly patients, enrolled under the SENIEUR protocol, and healthy adult controls. The aim of the study was to ascertain whether the reduced immune response, described during aging, is linked to deficient production of IL-2 or to its receptorial deficit, or if the reduced serum IL-2 concentrations observed during aging can be used as a biological immunodeficiency marker. The results obtained did not show any significant differences between the study groups, even if mean values were slightly decreased in the elderly group, as compared to the adult one. This finding does not justify the age-dependent deficiency of the immune response, i.e., to explain this condition, one needs another pathogenetic hypothesis. It is suggested that one such hypothesis could be the alteration of IL-2 receptors which undergo major cleavage and minor re-expression in the elderly, causing this way some receptorial changes with consequent reduction of T-helper activation.     

Apocynin decreases hydrogen peroxide and nirtate concentrations in exhaled breath in healthy subjects

The imbalance between reactive oxygen species (ROS) synthesis and antioxidants might be involved in the pathogenesis of many inflammatory diseases. NADPH oxidase, an enzyme responsible for ROS production, may represent an attractive therapeutic target to inhibit, for the treatment of these diseases.Apocynin is an inhibitor of activation of NADPH oxidase complex present in the inflammatory cells.In double blind, placebo-controlled, cross-over study, we investigated the effect of nebulized apocynin on ROS synthesis in 10 nonsmoking healthy volunteers. Apocynin (6 ml of 0.5 mg/ml) was administered by nebulization and its effects on H₂O₂, NO₂^? and NO₃^? generation were assessed after 30, 60 and 120 min by collecting exhaled breath condensate (EBC) samples using an EcoScreen analyzer. Additionally, respiratory parameters have been evaluated, utilizing spirometry and DLCO. We also analyzed peripheral blood differential counts and NO₂^? serum level, cough scale control and blood pressure as safety parameters.Apocynin caused reduction of H₂O₂ concentration in EBC as compared to placebo, after 60 min. of inhalation (0.18 μM vs. 0.31 μM, p < 0.05) as well as after 120 min. (0.2 μM vs. 0.31 μM, p < 0.05). Similarly, apocynin significantly decreased concentration of NO₃^? as compared to placebo, after 60 and 120 min. (6.8 μM vs. 14.4 μM and 6.5 μM vs. 14.9 μM respectively, p < 0.05). Apocynin was well tolerated and no adverse events have been observed throughout the study.Thus, as apocynin significantly influence ROS concentration, it might have also antiinflammatory properties. As it is safe, it may have a potential to become a drug in airway inflammatory diseases treatment.     

Changes in plasma triacylglycerol concentrations after sequential lunch and dinner in healthy subjects

OBJECTIVES: The present study examines the kinetic of plasma triacylglycerol (TAG) after sequential ingestion of lunch and dinner as well as the contribution of dietary fat ingested at lunch to subsequent post-dinner TAG composition. METHOD: Six healthy subjects were included. After standardized breakfast (7: 30AM), 2 mixed meals with fat loads composed of 44 g olive oil (rich in oleic acid) at lunch (12PM) and 44 g sunflower oil (rich in linoleic acid) at dinner (7PM) were ingested. [1-13C] palmitate was added in lunch only. Plasma TAG and chylomicron-TAG (CMTAG) levels were measured sequentially after meals. [1-13C] palmitate enrichment and concentrations of oleic acid and linoleic acid were measured in all lipid fractions. RESULT: Post-dinner plasma TAG peak was delayed as compared to lunch (3 hours vs 1 hour, p=0.002) whereas the magnitude of the postprandial peaks was not significantly different between lunch and dinner (2.4+/-0.3 vs 2.0+/-0.4 mmol/L, p=0.85). [1-13C] palmitate enrichment was maximal 5 hours after lunch in all lipid fractions and decreased slowly thereafter. After dinner ingestion, the rate of decline of [1-13C] palmitate enrichment plateaued during the first 60 minutes. Oleic acid increased slightly and immediately after dinner and remained the predominant fatty acid in all lipid fractions during the first hour after dinner. A delayed peak of plasma and CM-TAG was observed after dinner as compared to lunch without difference in the magnitude of peaks. CONCLUSION: The contribution of dietary fat ingested at lunch to post-dinner lipemia is confirmed despite the relatively long lasting interval between the 2 meals (7 h) and the absence of any early peak of plasma TAG after dinner.     

Steady-state plasma and intrapulmonary concentrations of levofloxacin and ciprofloxacin in healthy adult subjects

STUDY OBJECTIVE: To determine the steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and ciprofloxacin. DESIGN: Multiple-dose, open-label, randomized pharmacokinetic study. PARTICIPANTS: Thirty-six healthy, nonsmoking adult subjects were randomized either to oral levofloxacin, 500 or 750 mg once daily for five doses, or ciprofloxacin, 500 mg q12h for nine doses. INTERVENTIONS: Venipuncture, bronchoscopy, and BAL were performed in each subject at 4 h, 12 h, or 24 h after the last administered dose of antibiotic. MEASUREMENT AND RESULTS: Mean plasma concentrations of levofloxacin and ciprofloxacin were similar to those previously reported. For once-daily dosing of levofloxacin, 500 mg, the mean (+/- SD) steady-state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 +/- 2.7 microg/mL, 6.5 +/- 2.5 microg/mL, and 0.7 +/- 0.4 microg/mL, respectively; AM concentrations were 97.9 +/- 80.0 microg/mL, 36.7 +/- 23.4 microg/mL, and 13.8 +/- 16.0 microg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state concentrations in ELF were 22.1 +/- 14.9 microg/mL, 9.2 +/- 5.3 microg/mL, and 1.5 +/- 0.8 microg/mL, respectively; AM concentrations were 105.1 +/- 65.5 microg/mL, 36.2 +/- 26.1 microg/mL, and 15.1 +/- 2.0 microg/mL, respectively. The concentrations of ciprofloxacin at 4 h and 12 h in ELF were 1.9 +/- 0.9 microg/mL and 0.4 +/- 0.1 microg/mL, respectively; AM concentrations were 34.9 +/- 23.2 microg/mL and 6.8 +/- 5.9 microg/mL, respectively. The differences in the ELF concentrations of the two levofloxacin groups vs those of the ciprofloxacin group were significant (p < 0.05) at each sampling time. CONCLUSIONS: Levofloxacin was more extensively distributed into intrapulmonary compartments than ciprofloxacin and achieved significantly higher steady-state concentrations in plasma and ELF during the 24 h after drug administration.     

Relationship between Hb and HbA2 concentrations in healthy and iron deficient subjects

Summary In 23 healthy subjects and in 115 patients with various degrees of chronic iron deficiency anaemia without congenital abnormalities of globin synthesis, Hb ranged from 3.4 to 16.3 g/100 ml. HbA₂ ranged from 0.0550 to 0.5250 g/100 ml. Hb and HbA₂ were statistically correlated, as shown by linear regression analysis (a=–0.1387; b=0.0372; r=0.8198; P<0.001). The second degree parabola was not statistically different, but it gave a biologically preferable Figure for intercept (a=–0.0006; b=0.0070; c=0.0015; r=0.8324; P<0.001). The second degree parabola was to be preferred also on the basis of previous literature results. Shortness of iron seems to reduce more the HbA₂ than the Hb levels.

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Zusammenfassung Es wird über die Beziehung zwischen Hb- und HbA₂-Konzentrationen in Gesunden und Eisenmangelpatienten berichtet. Untersucht wurden 23 gesunde Personen und 113 Patienten mit unterschiedlicher Eisenmangelanämie.Die für HbA₂ gefundenen Werte liegen zwischen 0,055 und 0,525/100 ml. Die Darstellung nach einer Gleichung zweiten Grades in Form einer Parabel unterschied sich nicht statistisch signifikant, vermittelte jedoch ein aus biologischer Sicht plastisches Bild. Die Parabeldarstellung erwies sich auch als vorteilhaft in bezug auf in der Literatur mitgeteilte Ergebnisse.

     

Basal and tolbutamide-induced plasma somatostatin in healthy subjects and in patients with diabetes and impaired glucose tolerance

Peripheral levels of basal and tolbutamide-induced somatostatin have been measured in patients with diabetes or impaired glucose tolerance (IGT) and compared with those in normal individuals. Basal somatostatin was significantly higher in patients with Type 1 diabetes than in age-matched control subjects. This increase was most pronounced at diagnosis, and appeared to be related to metabolic control in insulin-treated patients. No increase was noted in patients with Type 2 diabetes or with IGT. Intravenous bolus injection of tolbutamide enhanced peripheral somatostatin levels in healthy volunteers in a biphasic manner. Patients with IGT also exhibited a biphasic response but the amplitude of the first phase was higher. No secretory response was detected in 27/29 Type 1 diabetic patients at diagnosis; a somatostatin response to tolbutamide became detectable again in Type 1 patients with normalization of their basal somatostatin levels but was then paradoxically related to poor blood glucose control. In Type 2 diabetes, basal somatostatin levels were similar to age-matched control subjects, but decreased upon intravenous tolbutamide administration.     

Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases

Plasma secretin concentrations were determined in healthy subjects and patients with duodenal ulcer, achlorhydria, and celiac sprue. Mean fasting plasma secretin concentrations in 26 healthy subjects and 26 duodenal ulcer patients were 6.7±0.5 and 10.2±1.2 pg/ml, respectively, and were significantly different (P<0.02). After ingestion of a standard meat meal, pyloric pH decreased to less than 4.5 within 15 min and plasma secretin concentrations significantly increased in all 52 subjects. In 14 subjects (seven healthy subjects and seven patients with duodenal ulcer), no significant rise in plasma secretin concentration occurred when pyloric pH was maintained at greater than 5.0 by intravenous cimetidine (600 mg) and intragastric antacid. In 10 achlorhydric patients, intragastric pH remained greater than 5.0 after the meal and plasma secretin concentrations did not change. However, plasma secretin concentrations increased significantly when 0.1 N HCl was infused in the stomach (25 mEq/hr) during the postprandial period. In all eight adult patients with celiac disease (seven untreated, one partially treated), pyloric pH remained less than 4.0 after a meal. Postprandial secretin concentrations did not increase significantly in six and showed a transient rise in two. These studies show that (1) plasma secretin concentration increases significantly after meals in healthy subjects and patients with duodenal ulcer; (2) neutralization of gastric acid and the achlorhydric state show no significant postprandial rise in plasma secretin concentration; (3) achlorhydric patients do not have a defect in secretin release in response to acid; and (4) failure of postprandial rise in plasma secretin in patients with celiac disease is attributed to impaired release of secretin and in achlorhydric patients it is attributed to lack of acid secretion.This work was supported by The Genesee Hospital Gastrointestinal Research Fund and U.S. Public Health Research Grant NIH AMDD 25962.     

Circulating somatostatin after oral glucose in hypothyroidism

The response of circulating somatostatin-like immunoactivity (SLI) to oral glucose and its relation to other pancreatic islet cell hormones were studied in 10 hypothyroid subjects before and after treatment. None of the patients suffered from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid subjects had higher fasting and stimulated SLI levels but lower fasting pancreatic glucagon levels. Integrated glucose and insulin responses following glucose ingestion were normal, but the peak insulin response was delayed to 120 min suggesting impaired pancreatic beta-cell response to oral glucose. On the other hand, the peak response of plasma C-peptide was higher probably because of a reduction in metabolic clearance. In both hypothyroid subjects and controls, a significant correlation was found between the maximal increment of SLI and the maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI is increased in hypothyroidism. The changes in SLI may be due to either an increased hormonal secretion or a reduced metabolic clearance in hypothyroidism. This elevated SLI might contribute to the slower gastrointestinal motility observed in hypothyroidism. Our data also suggest that the reduction in glucagon secretion may be secondary to the increase in circulating SLI.     

Plasma concentrations of glucagon during hyperglycemic clamp with or without somatostatin infusion in obese subjects

Summary The aim of the present study was to evaluate whether the inhibitory effect on pancreatic A-cell exerted by hyperglycemic hyperinsulinemia and/or by somatostatin administration is impaired in human obesity. For this purpose plasma glucagon concentrations were measured in 8 obese and 8 nonobese nondiabetic subjects during a 4-h hyperglycemic clamp. Synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min during the third hour of the study. Fasting plasma glucagon was higher in obese than in nonobese subjects (242±32vs 163±15 pg/ml, p<0.05) (mean±SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100–120 min of the study) plasma glucagon averaged 195±26 pg/ml in obese and 122±13 pg/ml in nonobese subjects (p<0.05), with a reduction of 19±3% in the former and 28±4% in the latter (p=n.s.). In both groups somatostatin infusion did not result in a further decrease in plasma glucagon, which averaged 192±27 pg/ml in obese and 123±16 pg/ml in nonobese subjects (p<0.05) in the 160–180 min period of the study. Also after discontinuing somatostatin infusion plasma glucagon levels did not change. These results suggest that in human obesity hyperglycemic hyperinsulinemia has a normal inhibitory effect on pancreatic A-cell and that somatostatin administration has no additive effect on hyperglycemia and hyperinsulinemia in either obese or nonobese nondiabetic subjects. Supported by grants n^o 83.02749.56, 84.03099.56, 85.00681.56, 86.01873.56, 83.02591.04, 85.00502.04 and 86.00102.04 fromConsiglio Nazionale delle Ricerche, Italy, and by grants fromMinistero della Pubblica Istruzione, Italy.     

Postprandial plasma concentrations of glycine and taurine conjugated bile acids in healthy subjects.

Fasting and postprandial plasma concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured by a high pressure liquid chromatography-enzymatic assay in nine healthy subjects. The mean value of each bile acid concentration increased significantly (2.4-4.7 times) in the postprandial period. The total glycine taurine ratio of 2.5 in the fasting state increased significantly to a maximum value of 3.3 at one to 1 1/2 hours postprandially and then declined. This shift in glycine taurine ratio shows, that the relative increase in concentrations of glycine conjugates exceeds the relative increase in concentrations of taurine conjugates in the early postprandial period, and supports the view that there is significant absorption of glycine conjugated bile acids from the proximal small intestine.     

Pigment gallstone composition in cirrhotic and noncirrhotic subjects

The composition of pigment gallstones from patients with and without cirrhosis was compared. Carbonate-containing pigment stones were distinguished from noncarbonate stones by infrared spectroscopy. Calcium was the major cation of each stone group. The major anion in noncarbonate pigment stones was bilirubinate or phosphate, but was carbonate in carbonate stones. The composition of pigment stones from cirrhotic and noncirrhotic patients was similar except that significantly less carbonate was present in carbonate stones, and less pigment (bilirubinate) was present in noncarbonate stones from noncirrhotics. These data suggest that irrespective of the presence of cirrhosis, the formation of noncarbonate pigment stones involves the selective precipitation of calcium bilirubinate and phosphate, whereas carbonate stone formation involves the selective precipitation of calcium carbonate.     

Effects of vitamin A administration on serum thyrotropin concentrations in healthy human subjects

Retinoids play an important role in the regulation of normal growth and development. Their biological action is mediated by a nuclear receptor that belongs to the steroid/thyroid hormone receptors superfamily. Retinoic acid has been shown to inhibit the secretion and synthesis of thyrotropin (TSH); however, little is known on the effects of retinoids on TSH secretion in normal human subjects. In the present study, we evaluated serum TSH concentration following both vitamin A (vit A) and the combined vit A and triiodothyronine (T(3)) administration. Basal and thyrotropin-releasing hormone (TRH)-stimulated TSH serum concentrations were measured in healthy young subjects in the following experimental conditions: (1) after 10 days of treatment with vit A orally administered as retinol at a dose of 50,000 IU/d; (2) after 10 days of oral placebo (PL) treatment; (3) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of PL treatment; and (4) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of vit A treatment. Serum TSH concentrations were also measured during vit A administration in healthy elderly subjects according to the following protocol: (1) after 10 days of treatment with PL; and (2) after 10 days of treatment with vit A at the same dose used for young subjects. In young subjects, basal serum TSH levels were found to be similar in the 4 different treatment conditions. In the same group of subjects, each of the 4 experimental conditions induced an increase in serum TSH, which rose from basal values of 1.80 +/- 0.31 to a peak of 11.92 +/- 1.75 microIU/mL (P <.001) during the PL treatment, from basal values of 1.81 +/- 0.22 to a peak of 10.81 +/- 1.00 microIU/mL (P <.001) during vit A treatment, from basal values of 1.72 +/- 0.28 to a peak of 9.92 +/- 1.10 microIU/mL (P <.001) during PL + T(3) treatment, and from basal values of 1.79 +/- 0.30 to a peak of 9.51 +/- 1.12 microIU/mL (P <.001) during vit A + T(3) treatment. The 2-way repeated measure analysis of variance revealed no significant differences among treatments. In old subjects, basal serum TSH levels were similar in the 2 experimental conditions and were not different from those observed in young subjects. In these subjects, serum TSH levels increased significantly in response to the TRH stimulus from basal values of 2.16 +/- 0.3 to a peak of 10.27 +/- 0.55 microIU/mL (P <.001) during PL treatment and from basal values of 2.10 +/- 0.51 to a peak of 7.82 +/- 1.4 microIU/mL (P <.001) during vit A treatment. No significant effects of treatment were found in this group of subjects on TRH-induced TSH levels; however, TSH responses were somewhat lower during vit A treatment with a difference close to statistical significance. These results suggest that TSH secretion is poorly affected by vit A administration in healthy human subjects; the data also indicate that any cooperation between T(3) and vit A is unlikely to occur in the regulation of TSH secretion.     

Plasma endothelin levels in cirrhotic subjects.

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.     

Plasma concentrations of growth hormone during hyperglycemic clamp with or without somatostatin infusion in obese subjects

It is known that obese subjects have a blunted GH secretory response to stimulation, but little is known about the inhibition of GH secretion in obesity. The present study was designed to evaluate the effects of obesity on the suppression of GH by hyperglycemia and/or somatostatin. Plasma GH concentrations were measured in eight nondiabetic obese subjects and eight nonobese healthy controls during a 4-h hyperglycemic clamp. During the third hour synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min. Baseline plasma GH levels were similar in obese and nonobese subjects (0.9 +/- 0.1 vs. 0.8 +/- 0.2 micrograms/L; mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma GH averaged 0.8 +/- 0.1 micrograms/L in obese patients and 0.4 +/- 0.1 micrograms/L in control subjects (P less than 0.01), with a reduction of 6 +/- 5% in the former and 35 +/- 10% in the latter (P less than 0.01). In both groups somatostatin infusion did not result in a further decrease in plasma GH. Discontinuation of the somatostatin infusion resulted in a rise in both groups; the increase was higher in nonobese subjects (8.1 +/- 3.8 vs. 2.3 +/- 0.9 micrograms/L in the period 220-240 min; P = NS). These results suggest that in human obesity, hyperglycemia has a diminished inhibitory effect on GH secretion, and somatostatin administration has no additional effect in either obese or nonobese nondiabetic subjects.     

Determinants of within-subject variation of fasting serum leptin concentrations in healthy subjects.

The hormone leptin is considered to contribute to body weight regulation through modulation of feeding behavior and energy expenditure. The aim of the present study was 1) to assess the day-to-day within-subject variation (biovariability) of serum leptin concentrations in healthy subjects and 2) to investigate whether this variation is associated with food intake, exercise, anthropometric measurements or various metabolic covariates (insulin, C-peptide and glucagon, glucose, lactate, 3-hydroxybutyrate (3-OHB), triglycerides, non-esterified-fatty acids and glycerol). Serum leptin levels were taken daily on 12 consecutive days after an overnight fast in 12 healthy subjects with a mean (SD) age of 22.7 (1.5) yr. and a BMI of 22.8 (1.6) kg/m2. Food intake, exercise, anthropometric measurements and various metabolic covariates were also determined during this period. The overall mean of serum leptin concentration was 33.3 pmol/L with a within-subject SD range of 27-41 pmol/L and a between-subject SD range of 18-61 pmol/L. The within-subject variance of serum leptin as a proportion of total variance was 9.5%. Within-subject variation of serum leptin concentrations is small in relation to between-subject variation in healthy, normal weight subjects. This has implications for the power of interventional or prospective studies. In men, 6.7% of the variation in serum leptin concentration was associated with body weight measured on the same day (p= 0.037). In women, however, 66% of the variation was negatively associated with 3-OHB measured on both the same and the previous day (p=0.0003 and 0.002), and positively associated with triglyceride concentration measured on the previous day (p=0.0017) and insulin measured on the same day (p=0.0002). Within-subject associations in women could be due to phasic changes in unmeasured variables, possibly related to the menstrual cycle or might suggest that energy balance may exert a delayed influence on serum leptin levels, with plasma 3-OHB and triglycerides acting as markers for the state of the fat stores that regulate leptin secretion. The differences between the genders remain unexplained, however.     

Effects of somatostatin on hepatic haemodynamics in the cirrhotic rat

Reports on the effects of somatostatin on hepatic haemodynamics in the cirrhotic patient have provided conflicting results. Therefore, we studied the effects of different modes and rates of somatostatin administration on hepatic haemodynamics in the cirrhotic rat. Portal pressure (PP), wedged hepatic venous pressure (WHVP), portal venous flow (PVF), liver blood flow (LBF) and systemic blood pressure were measured in rats with dimethylnitrosamine-induced cirrhosis. Somatostatin was administered as a rapid injection, a continuous infusion or as a bolus dose followed by a constant infusion. One group of rats with a previously constructed portacaval shunt received a bolus dose of somatostatin followed by a constant infusion. A rapid injection of somatostatin was attended by a rapid and significant fall in all the haemodynamic parameters measured (p less than 0.01). Continuous infusion of somatostatin [4 or 8 micrograms/kg body weight (BW) h] resulted in a gradual but significant reduction in PP, WHVP, PVF and LBF (p less than 0.05), but had no effect on systemic blood pressure. A bolus dose of somatostatin (2, 4 or 8 micrograms/kg BW over 2 min) resulted in a rapid decrease in PP, WHVP, PVF and LBF (p less than 0.01), the decreases being maintained by continuous infusion. In rats with a portacaval shunt a bolus dose of somatostatin (8 micrograms/kg BW) resulted in a rapid fall in WHVP and LBF, the decrease being maintained by a continuous infusion (8 micrograms/kg BW/h).(ABSTRACT TRUNCATED AT 250 WORDS)