Pancreatic α cell function in the fetal and newborn pig

1986 ◽  
Vol 108 (1) ◽  
pp. 137-142 ◽  
Author(s):  
M. Silver ◽  
A. L. Fowden ◽  
R. S. Comline ◽  
S. R. Bloom
Keyword(s):  
Plasma Concentration ◽  
Gestational Age ◽  
Cell Function ◽  
Plasma Concentrations ◽  
In Utero ◽  
Plasma Glucagon ◽  
Arginine Infusion ◽  
Newborn Piglets ◽  
Ph Values ◽  
The Mean

ABSTRACT Plasma glucagon concentrations were measured in chronically catheterized fetal pigs during the last third of gestation and compared with the values observed in anaesthetized fetuses of similar gestational age. The mean plasma concentration of glucagon in the chronically catheterized fetuses was 10·0 ± 1·4 (s.e.m.) pmol/l (n = 11; term = 114 ± 2 days). Concentrations were increased after catheterization and fell to baseline values within 48 h of surgery. Arginine infusion evoked a rapid release of glucagon in chronically catheterized fetuses between 105 and 108 days of gestation; the mean maximum increment in plasma glucagon was 15·4 ± 4·5 pmol/l (n = 5). Plasma glucagon concentrations increased with increasing gestational age in both anaesthetized and chronically catheterized fetuses. Between 95 and 110 days of gestation, glucagon levels were significantly higher in anaesthetized fetuses than in chronically catheterized animals with similar normal pH values. Catheterization and prematurity had no apparent effect on plasma glucagon levels at birth. The plasma concentrations at birth were similar to those observed in the chronically catheterized fetuses in utero provided the piglets did not become acidotic during delivery. Significantly higher plasma levels of glucagon were found in newborn piglets with acidaemia (pH < 7·3) than in piglets with normal pH values at birth (pH > 7·3). When all the data from the newborn piglets were combined, there was a significant negative correlation (r= − 0·79, n = 39, P < 0·01) between blood pH and the plasma concentration of glucagon at birth. These observations demonstrate that the fetal α cells are functional and responsive in utero and at birth. J. Endocr. (1986) 108, 137–142

scholarly journals Influence ofABCC2andABCC4Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients

2015 ◽  
Vol 59 (6) ◽  
pp. 3240-3245 ◽  
Author(s):  
Kanokrat Rungtivasuwan ◽  
Anchalee Avihingsanon ◽  
Narukjaporn Thammajaruk ◽  
Siwaporn Mitruk ◽  
David M. Burger ◽  
...  
Keyword(s):  
Body Weight ◽  
Multivariate Analysis ◽  
Plasma Concentration ◽  
Protease Inhibitors ◽  
Demographic Data ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
The Mean

ABSTRACTTenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded byABCC2andABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms ofABCC2andABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and theABCC44131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having theABCC44131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)

Diurnal changes in the plasma concentrations of LH and hypothalamic contents of LHRH-I and LHRH-II in the domestic hen

1991 ◽  
Vol 130 (3) ◽  
pp. 457-462 ◽  
Author(s):  
S. C. Wilson ◽  
R. T. Gladwell ◽  
F. J. Cunningham
Keyword(s):  
Plasma Concentration ◽  
Diurnal Rhythm ◽  
Laying Hens ◽  
Plasma Concentrations ◽  
Posterior Hypothalamus ◽  
Anterior Hypothalamus ◽  
Diurnal Changes ◽  
The Mean ◽  
The Times ◽  
Lh Secretion

ABSTRACT Diurnal changes of LH secretion in sexually immature hens of 9, 11, 13 and 15 weeks of age consisted of 25–40% increases in the mean concentrations of LH in plasma between 15.00 and 18.00 h, i.e. between 2 h before and 1 h after the onset of darkness. During this time there was a tendency for the mean contents of LHRH-I in the anterior hypothalamus and posterior hypothalamus to increase by 21–74% and 20–56% respectively. In hens of 9 and 15 weeks, diurnal changes in the plasma concentration of LH closely paralleled those of LHRH-I content in the posterior hypothalamus. In contrast, the diurnal rhythm of LH secretion in hens of 11 and 13 weeks was more marked and plasma concentrations of LH continued to rise steeply between 18.00 and 21.00 h, i.e. between 1 and 4 h after the onset of darkness. At 11 weeks, this was associated with a reduction (P<0·01) in the contents of LHRH-I and LHRH-II, particularly in the anterior hypothalamus. In laying hens, a diurnal decline (P<0·01) in the plasma concentration of LH between 1 and 4 h after the onset of darkness was preceded by a fall (P<0·05) in the content of LHRH-I in the posterior hypothalamus and in the total hypothalamic content of LHRH-II (P<0·01). In all groups of hens, irrespective of the times of day at which tissue was taken, significant (P<0·05–<0·001) correlations between the contents of LHRH-I and LHRH-II in the anterior hypothalamus were observed. It is concluded that a diurnal rhythm of release of LHRH-I may drive the diurnal rhythm of LH secretion. Thus, in sexually immature hens of 9 and 15 weeks and laying hens in which diurnal changes in plasma LH were small there were parallel changes in the content of LHRH-I in the posterior hypothalamus. However, where the plasma concentration of LH was increased substantially, as at 11 weeks, there was a decline in the hypothalamic contents of LHRH-I. A simultaneous fall in the hypothalamic content of LHRH-II raises the possibility of a causal relationship between the activities of LHRH-II, LHRH-I and the release of LH. Journal of Endocrinology (1991) 130, 457–462

Evaluation of target attainment of oral posaconazole suspension in immunocompromised children

2019 ◽  
Vol 75 (3) ◽  
pp. 726-729
Author(s):  
Tony Lai ◽  
Jan-Willem Alffenaar ◽  
Alison Kesson ◽  
Sushil Bandodkar ◽  
Jason A Roberts
Keyword(s):  
Retrospective Study ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Invasive Fungal Disease ◽  
Target Attainment ◽  
Breakthrough Infection ◽  
H2 Antagonist ◽  
Starting Dose ◽  
Histamine H2 Antagonist ◽  
The Mean

Abstract Background Posaconazole is a broad-spectrum antifungal that is not licensed for use in children &lt;13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. Objectives To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children &lt;13 years of age. Patients and methods We performed a retrospective study of immunocompromised children &lt;13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. Results A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P&lt;0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). Conclusions The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.

Increased peripheral venous somatostatin concentration and decreased glucagon response to arginine in patients with insulin dependent diabetes mellitus without residual B-cell function Increased plasma SRIF in IDDM

1985 ◽  
Vol 109 (4) ◽  
pp. 517-521 ◽  
Author(s):  
S. Skare ◽  
K. Dahl-Jørgensen ◽  
K. F. Hanssen ◽  
N. Norman
Keyword(s):  
B Cell ◽  
Cell Function ◽  
Islet Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Plasma Glucagon ◽  
Arginine Infusion ◽  
B Cell Function ◽  
Insulin Dependent ◽  
Normal Controls

Abstract. The glucagon response to insulin hypoglycaemia is frequently reduced in patients with IDDM. In the present study arginine infusion, thought to act directly on the islet cells, was used to stimulate somatostatin (SRIF) and glucagon in IDDM without residual B-cell function. Thirteen IDDM patients' were compared with 13 sex-and age matched normal controls following an arginine infusion. The plasma SRIF concentrations in the 'IDDM group' and normal controls increased from 24.2 ± 2.5 to 31.1 ± 3.9 pmol/l (P <0.01) and 19.7 ± 1.7 to 23.9 ± 3.4 pmol/l respectively after 10 min (P < 0.01). The plasma glucagon concentrations increased from 27 ± 4.7 to 176 ±23.1 pmol/l (P < 0.01) and 36 ± 5.0 to 302 ± 31.9 pmol/l (P <0.01) respectively after 20 min. Thus, in long standing IDDM without residual B-cell function, increased plasma SRIF concentrations are found and the glucagon response to arginine is reduced. The last observation further explains why these patients are especially vulnerable to hypoglycaemia.

Plasma Inorganic Fluoride Concentrations after Sevoflurane Anesthesia in Children

1996 ◽  
Vol 84 (2) ◽  
pp. 348-353. ◽  
Author(s):  
M. F. Levine ◽  
J. Sarner ◽  
J. Lerman ◽  
P. Davis ◽  
N. Sikich ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Elective Surgery ◽  
Plasma Concentrations ◽  
Sevoflurane Anesthesia ◽  
Inorganic Fluoride ◽  
Time Curve ◽  
Plasma Urea ◽  
The Mean ◽  
Group 2

Background Sevoflurane is degraded in vivo in adults yielding plasma concentrations of inorganic fluoride [F-] that, in some patients, approach or exceed the 50- micron theoretical threshold for nephrotoxicity. To determine whether the plasma concentration of inorganic fluoride [F-] after 1-5 MAC x h sevoflurane approaches a similar concentration in children, the following study in 120 children scheduled for elective surgery was undertaken. Methods Children were randomly assigned to one of three treatment groups before induction of anesthesia: group 1 received sevoflurane in air/oxygen 30% (n = 40), group 2 received sevoflurane in 70% N2O/30% O2 (n = 40), and group 3 received halothane in 70% N2O/30% O2 (n = 40). Mapleson D or F circuits with fresh gas flows between 3 and 61/min were used Whole blood was collected at induction and termination of anesthesia and at 1, 4, 6, 12, and 18 or 24 h postoperatively for determination of the [F-]. Plasma urea and creatinine concentrations were determined at induction of anesthesia and 18 or 24 h postoperatively. Results The mean (+/- SD) duration of sevoflurane anesthesia, 2.7 +/- 1.6 MAC x h (range 1.1-8.9 MAC x h), was similar to that of halothane, 2.5 +/- 1.1 MAC x h. The peak [F-] after sevoflurane was recorded at 1 h after termination of the anesthetic in all but three children (whose peak values were recorded between 4 and 6 h postanesthesia). The mean peak [F-] after sevoflurane was 15.8 +/- 4.6 microns. The [F-] decreased to &lt;6.2 microns b 24 h postanesthesia. Both the peak [F-] (r2 = 0.50) and the area under the plasma concentration of inorganic fluoride-time curve (r2 = 0.57) increased in parallel with the MAC x h of sevoflurane. The peak [F-] after halothane, 2.0 +/- 1.2 microns, was significantly less than that after sevoflurane (P&lt;0.00012) and did not correlate with the duration of halothane anesthesia (MAC x h; r2 = 0.007). Plasma urea concentrations decreased 24 h after surgery compared with preoperative values for both anesthetics (P&lt;0.01), whereas plasma creatinine concentrations did not change significantly with either anesthetic. Conclusions It was concluded that, during the 24 h after 2.7 +/- 1.6 MAC x h sevoflurane, the peak recorded [F-] is low (15.8 microns), F- is eliminated rapidly, and children are unlikely to be at risk of nephrotoxicity from high [F-].

Prophylactic Disopyramide: Its Clinical Effects Related to Plasma Concentration in Myocardial Infarction

1980 ◽  
Vol 8 (5) ◽  
pp. 314-320 ◽  
Author(s):  
Rowan Mary Hillson ◽  
E Boyd ◽  
J Cunningham
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plasma Concentration ◽  
Plasma Level ◽  
Plasma Concentrations ◽  
Double Blind Study ◽  
Clinical Effects ◽  
Number Of Patients ◽  
Wide Range ◽  
The Mean

Sixty-three patients, fifty-two with acute myocardial infarction and eleven with ischaemic heart disease or non-cardiac chest pain, were given either disopyramide phosphate or placebo, orally, in a randomized double-blind study. Thirty-two patients on disopyramide (twenty-six with acute myocardial infarction) received an initial dose of 300 mg followed by 150 mg six-hourly for 3 days. There was a reduction in the number of patients with cardiac dysrhythmias on the first 3 days following infarction in subjects taking disopyramide as compared with controls. This reduction was not statistically significant. There was a significant reduction in the mean ectopic count per hour in patients taking disopyramide compared with those taking placebo on the second day only (p < 0.005). Urinary retention, dry mouth and jaundice were recorded more frequently in the test group. There were wide ranges of pre-dose plasma concentrations on all 3 days. (Day 1: 1.3 to 7.7 μg per ml. Day 2: 2.5 to 8.9 μg/ml and Day 3: 2.5 to 11.5 μg per ml). The mean plasma concentration of disopyramide was higher but not significantly so, in the treatment group without evidence of dysrhythmias than those with dysrhythmias (3.8 ± S.D. 1.5 μg/ml and 3.0 ± 0.8 μg/ml respectively). The mean plasma level in patients who required anti-emetic therapy was significantly lower than those who did not (2.8 ± 0.8 μg/ml and 3.8 ± 1.9 μg/ml respectively, p < 0.025). The wide range of plasma levels observed is probably due in part to irregular absorption with vomiting after myocardial infarction. If disopyramide is to be used prophylactically following myocardial infarction, a therapeutic plasma level will be achieved quickly in all cases only by giving an intravenous starting dose.

PANCREATIC β-CELL FUNCTION IN THE FETAL FOAL AND MARE

1980 ◽  
Vol 87 (2) ◽  
pp. 293-301 ◽  
Author(s):  
ABIGAIL L. FOWDEN ◽  
R. J. BARNES ◽  
R. S. COMLINE ◽  
MARIAN SILVER
Keyword(s):  
Gestational Age ◽  
Glucose Concentration ◽  
Cell Function ◽  
Insulin Concentration ◽  
Β Cell ◽  
Exogenous Glucose ◽  
Β Cell Function ◽  
The Mean ◽  
Mean Glucose ◽  
Mean Concentration

Insulin secretion and the factors influencing β-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal β cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7·5 ± 0·5 (s.e.m.) μu./ml (n = 20) which was significantly less than the corresponding maternal value of 49·0 ± 5·0μu./ml (n = 20, P<0·01). The insulin concentration in non-pregnant horses was 24·5 ± 1·5 μu./ml (n = 5) which was significantly less than the value in the pregnant animals (P<0·01). However, there was no significant difference in the mean glucose concentration between the groups of adult animals. The insulin concentration was related to the endogenous glucose level in both adult and fetal horses. Wide variation in the maternal insulin concentration was observed above a glucose concentration of about 5·0 mmol/l. The mean concentration of insulin in pregnant mares decreased with increasing gestational age while the mean glucose concentration remained unaltered throughout the second half of gestation. There was no change in the basal concentrations of insulin or glucose in the fetus with gestational age although the fetal β-cell response to exogenous glucose appeared to increase with increasing fetal age after 270 days of gestation (term 330 days). There was a significant arterio-venous difference in the concentration of insulin across the gravid uterus in the mare when the arterial insulin level was greater than 30 μu./ml. Below this value, there was no consistent uptake of insulin by the uterus. The observations are discussed in relation to the regulation of insulin release in utero and the effects of pregnancy on maternal β-cell function.

EFFECTS OF TEMPERATURE AND FEED INTAKE ON PLASMA CONCENTRATION OF THYROID HORMONES IN BEEF CATTLE

1979 ◽  
Vol 59 (4) ◽  
pp. 655-661 ◽  
Author(s):  
R. J. CHRISTOPHERSON ◽  
H. W. GONYOU ◽  
J. R. THOMPSON
Keyword(s):  
Plasma Concentration ◽  
Thyroid Hormone ◽  
Feed Intake ◽  
Plasma Concentrations ◽  
Beef Steers ◽  
Outdoor Temperature ◽  
Cold Environments ◽  
Hormone Responses ◽  
The Mean ◽  
Effects Of Temperature

In each of two experiments, plasma concentrations of thyroxine (T4) and triiodothyronine (T3) and the Free Thyopac Index (FTI) were determined, at intervals during winter, in beef steers housed either indoors in a heated barn or in outdoor pens. During experiment 2, a comparison was also made of the effects of four feed intake levels ranging from one to two times maintenance. In both experiments, plasma concentrations of T4 and FTI values were higher in steers kept outdoors than those kept indoors. The highest plasma T4 concentrations and FTI values were recorded in outdoor steers on a maintenance level of feed intake during February when the mean outdoor temperature was −15 °C. Under these circumstances, increasing the level of feed intake to twice maintenance reduced plasma T4 concentrations and FTI values. Level of feed intake had no effect on either plasma T4 or FTI values in steers kept in a heated barn. Plasma T3 concentrations were higher in the outdoor than the indoor steers during experiment 2. Reducing feed intake from twice maintenance to maintenance levels resulted in a decrease in plasma T3 concentrations in steers kept outdoors, but not in those kept indoors in a heated barn. These results indicate that thyroid hormone responses of cattle to cold environments are influenced by the level of feed intake.

Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly

1986 ◽  
Vol 111 (2) ◽  
pp. 145-150
Author(s):  
Ståle Skare ◽  
Vera Kriz ◽  
Kristian F. Hanssen
Keyword(s):  
Serum Insulin ◽  
Plasma Glucagon ◽  
Serum Growth Hormone ◽  
Arginine Infusion ◽  
Before And After ◽  
The Mean ◽  
Active Acromegaly ◽  
The Difference ◽  
Islet Cell Hormones ◽  
Normal Controls

Abstract. Ten acromegalic patients, 28–71 years old, were compared with 10 normal controls, 21–39 years old. In another study, 7 patients with active acromegaly, 19–70 years old, were investigated before and 4–9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min). Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF)) was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 ± 3.8 and 16.6 ± 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 ± 23.9 and 63 ± 11.8 mU/1, respectively) and lower plasma glucagon (peak values 171 ± 29.0 and 310 ± 52.7 pmol/l, respectively). Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 ± 2.6 and 15.2 ± 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 ± 38.8 and 91 ± 24.9 mU/1, respectively). Plasma glucagon was similar before and after the operation (peak values 143 ± 23.4 and 127 ± 22.7 pmol/l, respectively). Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.

Plasma glucagon in pups, decreased by fasting, unaffected by somatostatin or hypoglycemia

1976 ◽  
Vol 231 (5) ◽  
pp. 1377-1382 ◽  
Author(s):  
G Hetenyi ◽  
N Kovacevic ◽  
SE Hall ◽  
M Vranic
Keyword(s):  
Plasma Concentration ◽  
Gastric Mucosa ◽  
Glucose Production ◽  
Immunoreactive Insulin ◽  
Alpha Cells ◽  
Plasma Glucagon ◽  
Basal Plasma ◽  
Adult Organism ◽  
The Mean ◽  
High Level

In pups less than 4 days old, the mean basal plasma immunoreactive glucagon (IRG) level was about 3 times higher than in adult dogs. This high level decreased with age, and in pups older than 12 days the mean plasma IRG level did not differ from that in adults. Insulin-induced hypoglycemia did not raise plasma IRG concentration in young pups. Fasting decreased plasma IRG in young, but not in older pups. This decrease is consistent with the decrease in gluconeogenesis and in contrast to the metabolic adjustments observed in the adult organism. In pups less than 7 days old, both the pancreas and gastric mucosa contained considerably more IRG than the normal value reported for adult dogs. Gastroduodenal IRG was immunologically indistinguishable from pancreatic glucagon. In pups, somatostatin did not decrease the plasma concentration of either IRG or immunoreactive insulin (IRI) and caused no change in plasma glucose or in the rates of glucose production and utilization calculated from experiments with tracers. The experiments indicate that in pups the pancreatic and gastric alpha-cells are unresponsive to stimuli normally effective in grown dogs.

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