Biliary transport maximum of tauroursodeoxycholate is twice as high as that of taurocholate in the rat

Biliary excretory transport maximum (Tm) and choleretic efficiency were compared for tauroursodeoxycholate and taurocholate in Wistar male rats. Under a continuous iv infusion of bile salts with a stepwise increase in infusion rate, the Tm of tauroursodeoxycholate was found to be two times higher (2.25±0.07 μmole/min/100 g body weight, n=8, mean±SD) than that of taurocholate (0.97±0.05 μmole/min/100 g body weight, n=14, p<0.001). On the other hand, the amount of bile water obligated by the excretion of 1μmole of tauroursodeoxycholate was significantly lower than that of taurocholate. (4.71±0.08 μl/μmole for tauroursodeoxycholate, vs. 9.27±0.76 μl/μmole for taurocholate, mean±SD, p<0.001). It was concluded that tauroursodeoxycholate can be excreted into the bile in male rats twice as efficiently as taurocholate. Furthermore, the higher efficiency in the choleretic property of ursodeoxycholate previously reported by Dumont et al. appears to be specific to free ursodeoxycholate and not to its taurine conjugate used in the present experiment.     

Left ventricular assist device: a functional comparison with heart transplantation

Background A growing number of patients with end-stage heart failure undergo implantation of ventricular assist devices as a bridge to heart transplantation. Objectives In this study we investigated whether functional and haemodynamic recovery after implantation is sufficient to warrant the use of them as long-term alternative to heart transplantation. Methods We compared peak VO₂ of a group of patients three months after implantation of a ventricular assist device and three months after heart transplantation. Furthermore, we analysed the degree of haemodynamic recovery, by comparing plasma levels of BNP and creatinine before and after implantation of the device. Results After implantation of a ventricular assist device, exercise capacity improved considerably; three months after implantation peak VO₂ was 20.0±4.9 ml/kg/min (52% of predicted for age and gender). After heart transplantation exercise capacity improved even further; 24.0±3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the three months after implantation, BNP plasma levels decreased from 570±307 pmol/l to 31±25 pmol/l and creatinine levels decreased from 191±82 μmol/l to 82±25 μmol/l, indicating significant unloading of the ventricles and haemodynamic recovery. Conclusion With regard to functional and haemodynamic recovery, the effect of implantation of a ventricular assist device is sufficient to justify its use as an alternative to heart transplantation. (Neth Heart J 2008;16:41-6.)     

Reference values for exhaled nitric oxide (reveno) study

Background

Human airway surface liquid (ASL) has abundant antimicrobial peptides whose potency increases as the salt concentration decreases. Xylitol is a 5-carbon sugar that has the ability to lower ASL salt concentration, potentially enhancing innate immunity. Xylitol was detected for 8 hours in the ASL after application in airway epithelium in vitro. We tested the airway retention time of aerosolized iso-osmotic xylitol in healthy volunteers.

Methods

After a screening spirometry, volunteers received 10 ml of nebulized 5% xylitol. Bronchoscopy was done at 20 minutes (n = 6), 90 minutes (n = 6), and 3 hours (n = 5) after nebulization and ASL was collected using microsampling probes, followed by bronchoalveolar lavage (BAL). Xylitol concentration was measured by nuclear magnetic resonance spectroscopy and corrected for dilution using urea concentration.

Results

All subjects tolerated nebulization and bronchoscopy well. Mean ASL volume recovered from the probes was 49 ± 23 μl. The mean ASL xylitol concentration at 20, 90, and 180 minutes was 1.6 ± 1.9 μg/μl, 0.6 ± 0.6 μg/μl, and 0.1 ± 0.1 μg/μl, respectively. Corresponding BAL concentration corrected for dilution was consistently lower at all time points. The terminal half-life of aerosolized xylitol obtained by the probes was 45 minutes with a mean residence time of 65 minutes in ASL. Corresponding BAL values were 36 and 50 minutes, respectively.

Conclusion

After a single dose nebulization, xylitol was detected in ASL for 3 hours, which was shorter than our in vitro measurement. The microsampling probe performed superior to BAL when sampling bronchial ASL.     

Insulin resistance in adolescents with Down syndrome: a cross-sectional study

Background

The prevalence of diabetes mellitus is higher in individuals with Down syndrome (DS) than in the general population; it may be due to the high prevalence of obesity presented by many of them. The aim of this study was to evaluate the insulin resistance (IR) using the HOMA (Homeostasis Model Assessment) method, in DS adolescents, describing it according to the sex, body mass index (BMI) and pubertal development.

Methods

15 adolescents with DS (8 males and 7 females) were studied, aged 10 to 18 years, without history of disease or use of medication that could change the suggested laboratory evaluation. On physical examination, the pubertal signs, acanthosis nigricans (AN), weight and height were evaluated. Fasting plasma glucose and insulin were analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was calculated using the HOMA method. The patients were grouped into obese, overweight and normal, according to their BMI percentiles. The EPIINFO 2004 software was used to calculate the BMI, its percentile and Z score.

Results

Five patients were adults (Tanner V or presence of menarche), 9 pubertal (Tanner II – IV) and 1 prepubertal (Tanner I). No one had AN. Two were obese, 4 overweight and 9 normal. Considering the total number of patients, HOMA was 1.7 ± 1.0, insulin 9.3 ± 4.8 μU/ml and glucose 74.4 ± 14.8 mg/dl. The HOMA values were 2.0 ± 1.0 in females and 1.5 ± 1.0 in males. Considering the nutritional classification, the values of HOMA and insulin were: HOMA: 3.3 ± 0.6, 2.0 ± 1.1 and 1.3 ± 0.6, and insulin: 18.15 ± 1.6 μU/ml, 10.3 ± 3.5 μU/ml and 6.8 ± 2.8 μU/ml, in the obese, overweight and normal groups respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5 ± 1.3, 1.4 ± 0.6 and 0.8 ± 0.0, and insulin: 13.0 ± 5.8 μU/ml, 7.8 ± 2.9 μU/ml and 4.0 ± 0.0 μU/ml, in the adult, pubertal and prepubertal groups respectively.

Conclusion

The obese and overweight, female and adult patients showed the highest values of HOMA and insulin.     

Long-Acting Subcutaneously Administered Insulin for Glycemic Control Immediately After Cardiac Surgery

ObjectiveTo test the hypothesis that subcutaneous administration of basal insulin begun immediately after cardiac surgery can decrease the need for insulin infusion in patients without diabetes and save nursing time.MethodsAfter cardiac surgery, 36 adult patients without diabetes were randomly assigned to receive either standard treatment (control group) or insulin glargine once daily in addition to standard treatment (basal insulin group). Standard treatment included blood glucose measurements every 1 to 4 hours and intermittent insulin infusion to maintain blood glucose levels between 100 and 150 mg/dL. The study period lasted up to 72 hours.ResultsThere were no differences in demographics or baseline laboratory characteristics of the 2 study groups. Mean daily blood glucose levels were lower in the basal insulin group in comparison with the control group, but the difference was not statistically significant (129.3 ± 9.4 mg/ dL versus 132.6 ± 7.3 mg/dL; P = .25). The mean duration of insulin infusion was significantly shorter in the basal insulin group than in the control group (16.3 ± 10.7 hours versus 26.6 ± 17.3 hours; P = .04). Nurses tested blood glucose a mean of 8.3 ± 3.5 times per patient per day in the basal insulin group and 12.0 ± 4.7 times per patient per day in the control group (P = .01). There was no occurrence of hypoglycemia (blood glucose level < 60 mg/dL) in either group.ConclusionOnce-daily insulin glargine is safe and may decrease the duration of insulin infusion and reduce nursing time in patients without diabetes who have hyperglycemia after cardiac surgery. (Endocr Pract. 2011;17: 558-562)     

Effect of a test meal,duodenal acidification,and tetragastrin on the plasma concentration of β-endorphin-like immunoreactivity in man

The effects of various test materials on plasma β-endorphin-like immunoreactivity (β-EpLI) were investigated in man using a specific radioimmunoassay developed by the authors. Plasma β-EpLI was determined after extraction by the acid/acetone method (recovery 73±5%). The intraassay and interassay coefficients of variation were 5.0% and 7.6%, respectively. The plasma concentrations of human β-EpLI in normal subjects were 11.6±4.0 pmol/l for men (n=23) and 10.7±4.8 pmol/l for women (n=27). Ingestion of a test meal (150 g of Campbell's condensed meat soup) resulted in a biphasic rise in plasma β-EpLI from the basal level of 4.4±1.0 pmol/l to 29.2±1.9 pmol/l after 5 min and 24.8±6.7 pmol/l after 90 min. Intraduodenal infusion of 115 ml of 0.1 M HCl over 10 min increased the plasma β-EpLI level from 8.7±0.5 pmol/l to 15.5±0.4 pmol/l at 10 min after the start of infusion, but the level rapidly returned to the initial value after the end of the infusion. Intramuscular injection of 4 μg/kg body weight of tetragastrin markedly stimulated gastric acid output and β-EpLI release, but pretreatment with 10 mg of histamine H₂ receptor antagonist inhibited the gastric acid output and plasma β-EpLI release induced by tetragastrin.These results indicate that β-EpLI release is stimulated by ingestion of meat soup, duodenal acidification and tetragastrin administration. It is suggested that gastric acid participates, at least in part, in postprandial release of β-EpLI, probably from the gastrointestinal tract.     

Contrast-enhanced versus non-enhanced three-dimensional echocardiography of left ventricular volumes

Background In three-dimensional echocardiography (3DE), individual endocardial trabeculae are not clearly visible necessitating left ventricular (LV) volumes to be measured by tracing the innermost endocardial contour. Ultrasound contrast agents aim to improve endocardial definition, but may delineate the outermost endocardial contour by filling up intertrabecular space. Although measurement reproducibility may benefit, there may be a significant influence on absolute LV volume measurements. Methods Twenty patients with a recent myocardial infarction and good ultrasound image quality underwent 3DE using the TomTec Freehand method before and during continuous intravenous contrast infusion. LV volumes were measured offline using TomTec Echo-Scan software. Results The use of contrast enhancement increased end-diastolic (110±35 vs. 144±53 ml; p<0.01) and end-systolic volume measurements (68±31 vs. 87±45 ml; p<0.01) significantly compared with non-contrast; the ejection fraction remained unchanged (40±13 vs. 41±14%, p=NS). Measurement reproducibility did not improve significantly, however. Conclusion Volumes measured by 3DE are significantly larger when ultrasound contrast is used. Possibly, intertrabecular space comprises a substantial part of the LV cavity. In the presence of an adequate apical acoustic window, ultrasound contrast does not improve LV volume measurement reproducibility. (Neth Heart J 2008;16:47-52.)     

Direct haemodynamic effects of pulmonary arteriovenous malformation embolisation

Background

Transcatheter embolisation is widely used to close pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT). Data on the direct cardiovascular haemodynamic changes induced by this treatment are scarce.

Objectives

We investigated the direct haemodynamic effects of transcatheter embolisation of PAVMs, using non-invasive finger pressure measurements.

Methods

During the procedure, blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and delta pressure/delta time (dP/dt) were continuously monitored using a Finometer®. Potential changes in these haemodynamic parameters were calculated from the pressure registrations using Modelflow® methodology. Absolute and relative changes were calculated and compared using the paired sample t-test.

Results

The present study includes 29 HHT patients (mean age 39?±?15 years, 11 men) who underwent transcatheter embolotherapy of PAVMs. The total number of embolisations was 72 (mean per patient 2.5). Directly after PAVM closure, SV and CO decreased significantly by ?11.9 % (p?=?0.01) and ?9.5 % (p?=?0.01) respectively, without a significant change in HR (1.8 %). Mean arterial blood pressure increased by 4.1 % (p?=?0.02), while the TPR and dP/dt did not increase significantly (5.8 % and 0.2 %, respectively).

Conclusions

Significant haemodynamic changes occur directly after transcatheter embolisation of PAVMs, amongst which a decrease in stroke volume and cardiac output are most important.     

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings

Background

Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.

Methods

A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI.

Results

No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.

Conclusion

Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.     

Embryonic stroke volume and cardiac output in the chick

Cine recordings of the hearts of chick embryos of 3 days and 2 hr to 4 days and 21 hr incubation were projected and measured. The measurements were converted to volumes. Stroke volume was determined from the difference in end diastolic and end systolic volume and multiplied by heart rate to yield cardiac output. Mean stroke volume was 0.0058 (±0.00036 SEM) mm³ per mg body wt; mean cardiac output was 0.956 (± 0.061 SEM) mm³/min per mg body wt. Stroke volume and cardiac output rose above their control values after intravascular injection of Ringer's solution, and even more so after the injection of dextran solution. The increases in stroke volume were due to increases in end diastolic volume, in the case of dextran injected embryos they occurred in spite of a simultaneous increase in end systolic volume. It is concluded that the rise in cardiac output with growth of the embryo is in large part due to an increase in stroke volume, and that the increase in stroke volume depends in part on the known increase in embryonic blood volume. The experiments further suggest that a rapid hydrostatic and osmotic equilibrium exists between embryonic blood plasma and an extra vascular compartment.     

Increased Whole‐Body Adiposity Without a Concomitant Increase in Liver Fat is Not Associated With Augmented Metabolic Dysfunction

Aim of this study was to determine whether an increase in adiposity, without a concomitant increase in intrahepatic triglyceride (IHTG) content, is associated with a deterioration in metabolic function. To this end, multiorgan insulin sensitivity, assessed by using a two‐stage hyperinsulinemic–euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusion, and very low‐density lipoprotein (VLDL) kinetics, assessed by using stable isotopically labeled tracer infusion and mathematical modeling, were determined in 10 subjects with class I obesity (BMI: 31.6 ± 0.3 kg/m²; 37 ± 2% body fat; visceral adipose tissue (VAT): 1,225 ± 144 cm³) and 10 subjects with class III obesity (BMI: 41.5 ± 0.5 kg/m²; 43 ± 2% body fat; VAT: 2,121 ± 378 cm³), matched on age, sex, and IHTG content (14 ± 4 and 14 ± 3%, respectively). No differences between class I and class III obese groups were detected in insulin‐mediated suppression of palmitate (67 ± 3 and 65 ± 3%, respectively; P = 0.635) and glucose (67 ± 3 and 73 ± 5%, respectively; P = 0.348) rates of appearance in plasma, and the insulin‐mediated increase in glucose disposal (218 ± 18 and 193 ± 30%, respectively; P = 0.489). In addition, no differences between class I and class III obese groups were detected in secretion rates of VLDL‐triglyceride (6.5 ± 1.0 and 6.0 ± 1.4 µmol/l·min, respectively; P = 0.787) and VLDL‐apolipoprotein B‐100 (0.40 ± 0.05 and 0.41 ± 0.04 nmol/l·min, respectively; P = 0.866), and plasma clearance rates of VLDL‐triglyceride (31 (16–59) and 29 (18–46) ml/min, respectively; P = 0.888) and VLDL‐apolipoprotein B‐100 (15 (11–19) and 17 (11–25) ml/min, respectively; P = 0.608). We conclude that increased adiposity without a concomitant increase in IHTG content does not cause additional abnormalities in adipose tissue, skeletal muscle, and hepatic insulin sensitivity, or VLDL metabolism.     

Changes of ghrelin and brain natriuretic peptide levels in systemic vascular resistance after cardiopulmonary bypass

The application of cardiopulmonary bypass (CPB) using a heart-lung machine in open heart surgery is associated with numerous pathophysiological changes in the vascular system and the neurohormonal environment. In this study our purpose was to investigate whether the hormones brain natriuretic peptide (BNP) and ghrelin are involved in changes in the systemic vascular resistance index (SVRI) after CPB, using data from 20 patients who had undergone coronary artery by pass grafting accompanied by CPB. Hemodynamic measurements were obtained using a thermodilution catheter and included cardiac index and systemic vascular resistance index. Blood samples were taken before CPB, after CPB, and at 0 and 24 h postoperatively. The blood levels of total and acylated ghrelin were quantified by radioimmunoassay. Blood levels of BNP were measured by a fluorescence immunoassay kit. The SVRI was significantly higher at the end of CPB and at 0 h postoperatively than before CPB (end of CPB: 4282±1035 dyne·s·cm^?5·m^?2, 0 h postoperatively: 3239±635 dyne·s·cm^?5·m^?2 vs. before CPB: 2289±330 dyne·s·cm^?5·m^?2, p<0.05). Total and acylated ghrelin levels decreased until 0 h postoperatively but the change was not statistically significant. However, at 24 h after surgery, they showed a statistically significant increase over the initial ghrelin values (total before CPB: 1413.71±287.93 pg/ml vs. 24 h postoperatively: 1736.85±236.89 pg/ml; acylated ghrelin before CPB: 55.85±25.53 pg/ml vs. 24 h postoperatively: 106.28±30.86 pg/ml; p<0.05 for both). BNP values were markedly lower after than before CPB (before CPB: 69.07±48 pg/ml vs. after CPB: 21.96±13 pg/ml, p<0.05) and reached a maximum value 24 h postoperatively (before CPB: 56.3±42 vs. after CPB: 454.7±229 pg/ml, p<0.05). There was a weak negative correlation between the changes in SVRI and total and acylated ghrelin levels after the CPB period, but this was not statistically significant. However, there was a statistically significant negative correlation between SVRI and BNP after CPB and at 24 h postoperatively (r:?0.709, p<0.01 and r:?0.649, p<0.03, respectively). Taken together, our results show that the observed initial increases in ghrelin and/or BNP in the postoperative period (at 24 h) might be causally related to the decrease in the SVRI in the same period. However, further investigations are needed to clarify the significance of this observation with respect to that of SVRI.     

Effects of insulin infusion on glucose kinetics in normal and burned guinea pigs

The effects of a constant infusion of insulin (12 mu/kg·min for 90 min) on glucose turnover (determined by means of the primed-constant infusion of 6-³H-glucose) was evaluated in normal and burned (50% BSA) guinea pigs (gp). In burned, untreated gp, the mean plasma glucose level (gl) was increased from 129±8.2 to 205±13.7 mg/dl 90 min after burning, whereas gl was 140±14.5 mg/dl in the burned + insulin-infused animals at 90 min. The insulin infusion reduced gl from 120±5.6 to 69±5.8 mg/dl in unburned gp; the rate of glucose appearance (R_a) was reduced and the metabolic clearance rate (MCR) was increased. In the B+I gp, the insulin effectively minimized the increase in R_a which followed burning in the burned, untreated gp. However, insulin did not increase the MCR of the burned + insulin-infused group above that of the burned, untreated group. On the day following the burn, the insulin infusion decreased gl in the burned gp to the same extent as in the unburned animals and also increased MCR. We concluded that whereas there was a lack of peripheral responsiveness to the insulin infusion in the first 90 min after burning (during the shock phase), no such lack of responsiveness was evident on the second day.     

Effect of truncal vagotomy on pancreatic polypeptide response after intravenous glucose administration

Intravenous glucose infusion was performed in six dogs with and without truncal vagotomy, and plasma pancreatic polypeptide (PP) responses were compared before and after truncal vagotomy. Following truncal vagotomy, basal PP levels decreased significantly from 286 ± 64 pg/ml (mean ± S.E.) to 94 ± 14 pg/ml (P < 0.05). Basal plasma insulin and blood glucose levels also tended to be lower, but not significantly. During the influsion of glucose, blood glucose concentrations rose rapidly in both groups and after 15 min reached peak values which were not significantly different from each other. In the vagotomized group the plasma insulin response to intravenous glucose infusion was significantly lower than in the control group. Following intravenous glucose loading, plasma PP concentrations decreased rapidly in both groups, but the PP level in the vagotomized group was suppressed only to 77 ± 4% of the basal level whereas in the control group it decreased to 45 ± 8%, significantly lower than in the vagotomized group (P < 0.01).These results suggest that basal PP is regulated by vagal tonus and that vagus controls, at least in part, suppression by intravenous glucose administration.     

Ontogeny of hypoxic modulation of cardiac performance and its allometry in the African clawed frog Xenopus laevis

The ontogeny of cardiac hypoxic responses, and how such responses may be modified by rearing environment, are poorly understood in amphibians. In this study, cardiac performance was investigated in Xenopus laevis from 2 to 25 days post-fertilization (dpf). Larvae were reared under either normoxia or moderate hypoxia (PO₂ = 110 mmHg), and each population was assessed in both normoxia and acute hypoxia. Heart rate (f _h ) of normoxic-reared larvae exhibited an early increase from 77 ± 1 beats min^?1 at 2 dpf to 153 ± 1 beats min^?1 at 4 dpf, followed by gradual decreases to 123 ± 3 beats min^?1 at 25 dpf. Stroke volume (SV), 6 ± 1 nl, and cardiac output (CO), 0.8 ± 0.1 μl min^?1, at 5 dpf both increased by more than 40-fold to 25 dpf with rapid larval growth (~30-fold increase in body mass). When exposed to acute hypoxia, normoxic-reared larvae increased f _h and CO between 5 and 25 dpf. Increased SV in acute hypoxia, produced by increased end-diastolic volume (EDV), only occurred before 10 dpf. Hypoxic-reared larvae showed decreased acute hypoxic responses of EDV, SV and CO at 7 and 10 dpf. Over the period of 2–25 dpf, cardiac scaling with mass showed scaling coefficients of ?0.04 (f _h ), 1.23 (SV) and 1.19 (CO), contrary to the cardiac scaling relationships described in birds and mammals. In addition, f _h scaling in hypoxic-reared larvae was altered to a shallower slope of ?0.01. Collectively, these results indicate that acute cardiac hypoxic responses develop before 5 dpf. Chronic hypoxia at a moderate level can not only modulate this cardiac reflex, but also changes cardiac scaling relationship with mass.     

Respiration and avoidance reaction of a cyprinid fishPseudogobio esocinus under hypoxia

A cyprinid fish,Pseudogobio esocinus showed gradual bradycardia at oxygen saturation (%) of less than 29.7±4.6 (1.89±0.29 ml/l of oxygen concentration), surfacing at 14.7±1.3 (0.94±0.09ml/l), drastic decrease of oxygen consumption at less than 14.2±0.8 (0.91 ±0.06ml/l) and asphyxia at 9.7±1.4 (0.62±0.09ml/l). The fish avoided water having low oxygen saturation of less than 54.0± 5.4 (3.38±0.30ml/l), and markedly at less than 26.2±3.4 (1.62±0.16 ml/l).     

Pulsatile infusion of luteinizing hormone-releasing hormone: Effects on luteinizing hormone secretion and ovarian function in prepuberal gilts

Ten intact and hypophysial stalk-transected (HST), prepuberal Yorkshire gilts, 112–160 days old, were subjected to a pulsatile infusion regimen of luteinizing hormone-releasing hormone (LHRH) to investigate secretion profiles of luteinizing hormone (LH) and ovarian function. A catheter was implanted in a common carotid artery and connected to an infusion pump and recycling timer, whereas an indwelling external jugular catheter allowed collection of sequential blood samples for radioimmunoassay of LH and progesterone. In a dose response study, intracarotid injection of 5 μg LHRH induced peak LH release (5.9 ± 0.65 ng/ml; mean ± SE) within 20 min, which was greater (P < 0.001) than during the preinjection period (0.7 ± 0.65 ng/ml). After HST, 5 μg LHRH elicited LH release in only one of three prepuberal gilts. Four intact animals were infused with 5 μg LHRH (in 0.1% gel phosphate buffer saline, PBS) in 0.5-ml pulses (0.1 ml/min) at 1.5-h intervals continuously during 12 days. Daily blood samples were obtained at 20-min intervals 1 h before and 5, 10, 20, 40, 60 and 80 min after one LHRH infusion. Plasma LH release occurred in response to pulsatile LHRH infusion during the 12-day period; circulating LH during 60 min before onset of LHRH infusion was 0.7 ± 0.16 ng/ml compared with 1.3 ± 0.16 ng/ml during 60 min after onset of infusion (P < 0.001). Only one of four intact gilts ovulated, however, in response to LHRH infusion. This animal was 159 days old, and successive estrous cycles did not recur after LHRH infusion was discontinued. Puberal estrus occurred at 252 ± 7 days in these gilts and was confirmed by plasma progesterone levels. These results indicate that intracarotid infusion of 5 μg LHRH elicits LH release in the intact prepuberal gilt, but this dosage is insufficient to cause a consistent response after HST.     

Hypercalcemia in association with a Leydig cell tumor in the rat: A model for tumor-induced hypercalcemia in man

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 ± 0.3 m mg/dl to 12.5 ± 0.4 mg/dl at day 10 and 16.4 ± 1.3 mg/dl (p<0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 ± 0.17 mg/d to 3.52 ± 0.72 mg/d (Day 12, p<0.01). Serum phosphate decreased from a baseline of 7.5 ± 0.3 mg/dl to 5.5 ± 0.6 mg/dl at day 13 (p<0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p<0.01). Calcitonin increased from 59 ± 2 pg/ml to 88 ± 9 pg/ml (p<0.01). The plasma prostaglandin E metabolite, 13, 14-dihydro-15-keto-PGE₂ increased from 407 ± 103 pg/dl to 647 ± 62 pg/ml (p<0.05) and the active Vit D compound 1, 25(OH)₂D increased from 94.8 ± 5.2 pg/ml to 162.3 ± 11.8 pg/ml (p<0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 ± 3 nmol/d to 172 ± 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.     

Increasing preweaning milk replacer supply affects postweaning energy metabolism of Holstein male calves

Male Holstein calves commonly receive minimal quantities of milk replacer (MR) to speed up weaning and reduce costs. Studies with Holstein female calves show that early life feed restriction affects energy metabolism later in life. Aiming to test this hypothesis, 120 Holstein bull calves (48.4 ± 2.2 kg of BW and 20 ± 3.2 d of age) housed in 24 pens were blocked and randomized to two treatments: A low calf MR allowance (LP) (two daily doses of 2 l each, 582 g/d of DM), or a high MR allowance (HP) (two daily meals of 4 l each, 1 164 g/d of DM). Calves were weaned at day 49 of the study and slaughtered at 32.8 ± 0.5 weeks of age. Throughout the study, animals had ad libitum access to a common compound feed, straw, and water. Twenty-four animals were randomly selected for an intravenous glucose tolerance test (IVGTT). The IVGTT was performed at week 6 and 12 of the study and consisted of an intravenous glucose infusion and sequential blood sampling up to 90 min after glucose infusions. Calves were heavier for HP until week 12, after which the difference disappeared. By design, the MR intake was higher in the HP group resulting in a higher energy intake and a higher average daily gain in the preweaning phase. Blood glucose curves were not different at week 6, but at week 12, 5 min after the infusion, glucose was higher in HP calves. Insulin curves were not different at week 6. Nevertheless, in week 12, a higher insulin concentration was observed for HP 5, 10, 15, 20, 30, 35, and 45 min’ postinfusion, indicating a higher requirement of insulin to control glycemia. Differences between HP and LP calves were also observed for the quantitative insulin sensitivity check index, maximum insulin concentration, and insulin delta at week 12. Blood glucose reached maximum concentration within 5–10 min of the IVGTT test, and the concentration was, on average, 8.58 and 10.80 mmol/l at weeks 6 and 12, respectively. Insulin reached maximum concentration within 10–15 min of the IVGTT, and concentrations were, on average, 33.32 and 32.61 μUI/ml at weeks 6 and 12, respectively. Doubling MR supply improved animal growth up to weaning, but these differences disappeared by the end of the feeding period. Despite similar responses to glucose infusions preweaning, higher milk supply seemed to decrease insulin sensitivity after weaning.     

Differential Regulation of Transferrin Receptor Gene Expression in Human Hemopoietic Cells: Molecular and Cellular Aspects

Abstract

As we have shown earlier (-)¹²⁵lodocyanopindolol (¹²⁵ICYP) binding to β-adrenoceptors (β-AR) in human mononuclear leucocytes (MNL) yields evidence for the existence of high affinity (B_hiaff) and low affinity (B_loaff) binding sites. We studied the regulation of these 2 classes of binding sites during 240 min of (-)-epinephrine (EPI) infusion (0.1 μg/kg/min) (n=8) in male healthy volunteers. Saturation experiments were performed on MNL membranes with ¹²⁵ICYP over a large concentration range (1–550 pmol/l). Binding parameters were calculated by computer analysis assuming 2 classes of binding sites. We found a preinfusion value of 830±50 [sites/cell] (K_D=1.5±0.2 pmol/l) of B_hiaff binding sites and 5210±510 [sites/cell] (K_D=420±80 pmol/l) of B_loaff. During EPI infusion we observed biphasic modulation of the B_hiaff and an inverse modulation of the B_loaff. After 40 min of EPI B_hiaff increased to 1970±280 [sites/cell] (K_D=4.2±0.8 pmol/l), whereas B_loaff decreased to 2720±280 [sites/cell] (K_D=140±70 pmol/l); despite constant plasma epinephrine concentration (PEC) after 240 min of EPI B_hiaff changed to 1310±240 [sites/cell] (K_D=2.8±1.0 pmol/l) vs. 4370±760 [sites/cell] (K_D=190±100 pmol/l) B_loaff. These results suggest an interdependent inverse modulation of the 2 classes of binding sites for ¹²⁵ICYP on MNL during EPI infusion.