Zinc plasma levels after oral zinc tolerance test in nonalcoholic cirrhosis

Zinc absorption was examined in 25 nonalcoholic cirrhotic patients using the oral zinc tolerance test and comparing results to a healthy control group. With 22.5 mg elementary zinc, the increase in plasma zinc was significantly lower in the cirrhotic patients than in the control group with P less than 0.01 in the first and second hours and P less than 0.05 in the fourth hour. The zinc malabsorption may result from an abnormal small intestinal mucosa. Indeed small intestinal biopsies in all patients showed partial shortening and prominent distension of villi and intense stromal edema with inflammatory cell infiltration of the lamina propria. However, it is not clear whether these intestinal changes are due to zinc deficiency or to portal hypertension. Thus zinc malabsorption appears to contribute to zinc deficiency in nonalcoholic cirrhotics and seems to result, in part, from pathological changes in the mucosa.     

Effect of technique of administration on plasma lidocaine levels

There are many clinical situations in which IV access is unavailable, and the endotracheal route is a valuable alternative route for drug therapy. The optimal technique of endotracheal drug administration, however, has not been determined. Twenty-nine dogs were divided into five groups and given endotracheal lidocaine at two doses, 2 mg/kg and 4 mg/kg, by differing techniques: control, undiluted lidocaine in a syringe was given as a bolus; needle, the drug was given through a needle attached to the syringe; dilution, lidocaine was diluted approximately 1:1 with normal saline and the entire dilution was given as a bolus; normal saline (NS) followup, lidocaine in a syringe was given as a bolus, followed immediately by an equal bolus of normal saline; and catheter, the drug was given through a catheter that was placed inside and extended just beyond the endotracheal tube. Mean plasma lidocaine levels (microgram/mL) at five minutes were as follows (at a 2-mg/kg endotracheal lidocaine dose): control, 0.64; needle, 0.0; dilution, 3.1; and (at a 4-mg/kg endotracheal lidocaine dose) control, 1.0; needle, 0.6; dilution, 6.2; NS followup, 1.9; and catheter, 1.9. At all time periods with either dose of lidocaine (2 or 4 mg/kg), the highest plasma lidocaine levels occurred with dilution and the lowest with the needle method. These results were highly significant (P less than .001). The highest plasma lidocaine levels may be attained by diluting the drug with normal saline. Higher levels were achieved when the drug was given through a catheter or when the drug was followed with a bolus of normal saline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radioimmunoassay for dexamethasone and its plasma levels after oral administration in patients with liver disease

Dexamethasone (DXM), one of the strong synthetic glucocorticoids, has been used widely for therapeutic purposes and for evaluation of the hypothalamic-pituitary-adrenal axis. However, information concerning the plasma concentrations of DXM and its metabolism in various liver diseases is limited. In this study, plasma DXM levels were examined in patients with chronic inactive hepatitis (CH), patients with liver cirrhosis (LC) and normal subjects (NR) after oral administration of one milligram DXM. Plasma DXM levels were measured directly in plasma extract, using reliable and sensitive radioimmunoassay (RIA). The antiserum was obtained by immunizing rabbits with DXM-3-oxime-bovine serum albumin conjugate. Standard curves for DXM were obtained over the range 10-5000 pg. The cross reactivity of endogenous steroids with DXM antiserum was less than 0.1%. In the group of NR, the peak of plasma DXM was 20.9 +/- 2.9 ng/ml within 1.3 +/- 0.4 hours after administration. Half time of its disappearance was 3.3 +/- 1.1 hours, and plasma DXM disappeared in 24 hours, remaining less than 1 ng/ml. In patients with CH and those with LC, the peak levels of DXM were 10.8 +/- 1.0 ng/ml and 10.5 +/- 0.5 ng/ml, respectively, and those values were significantly lower than those of NR. Half time of DXM disappearance in patients with CH and in those with LC were 6.2 +/- 0.6 and 6.3 +/- 0.6 hours, respectively, significantly prolonged compared with that of NR. Although DXM metabolism was impaired in CH as well as in LC, the retention rate of indocyanine green (ICG) at 15 minutes in CH was found within the normal range, 10.0 +/- 1.1%, respectively. These results might suggest that the impaired DXM metabolism in patients with chronic liver disease may be affected not only by the decreased hepatic blood flow but also by some other factors.     

Effect of oral glucose administration on ghrelin levels in obese children

OBJECTIVE: Coexpression of GH secretagogue receptor and ghrelin in the pancreas suggests that this peptide is involved in glucose metabolism. Previous reports in adult humans have demonstrated that plasma ghrelin levels decrease after oral glucose administration. However, no data are available in children. Therefore, the aim of this study was to analyze the response of plasma ghrelin levels in obese children after oral glucose administration. SUBJECTS AND METHODS: Twenty-eight obese children ranging from Tanner I to Tanner V were studied. All subjects were given 0.75 g/kg (maximum 75 g) glucose solution after overnight fasting. Ghrelin, insulin, glucose and IGF-binding-protein-1 were determined at 0, 30, 60 and 120 min of the oral glucose tolerance test (OGTT). RESULTS: Basal plasma ghrelin levels were significantly lower than in the respective control groups. These levels decreased significantly during OGTT in obese children, reaching a nadir of 28+/-9% at 60 min in parallel with the maximum increase in glucose levels and previous to maximum insulin levels. CONCLUSION: The rapid fall in plasma ghrelin concentration in obese children after glucose load suggests a mechanism for the control of appetite after food intake.     

Effect of vagotomy on insulin release after oral and intravenous glucose administration.

In 9 non-diabetic, non-obese patients, oral and intravenous glucose tolerance tests were carried out before and after vagotomy, and the serum insulin was determined. The potentiating effect on insulin release of orally administered glucose was not abolished by total vagotomy, meaning that vagal mechanisms are not likely to play a major role in this potentiation in man.     

Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate.

Plasma testosterone and androstenedione levels in men were measured after oral administration of free testosterone and testosterone undecanoate. Both androgens were determined by simultaneous, specific radioimmunoassays after separation and isolation by thin layer chromatography. While free unesterified testosterone had no effect on plasma androgen levels, a striking increase of both testosterone and androstenedione levels was noted after administration of testosterone undecanoate, which is otherwise only achieved by parenteral testosterone application. This effect of testosterone undecanoate is probably due to absorption via the lymph rather than via the portal vessels so that peripheral circulation is reached before metabolism in the liver. Testosterone undecanoate promises to be an effective medication for oral androgen replacement.     

Plasma levels of colchicine after oral administration of a single dose

Plasma colchicine levels have been measured serially after the oral administration of 1.0 mg of the drug to ten volunteer subjects. Peak colchicine concentrations averaged $\text{0.323 ± 0.173 μ}\text{g}\text{100}\text{ml}$. Two populations were evident within the group, one with highest concentrations $\text{1}\text{2}\text{hr}$ after administration, and a second with highest concentrations 2 hr after administration of colchicine by mouth.     

Effect of oral zinc supplements on growth, hormonal levels, and zinc in healthy short children

13 short children aged 7-13 years who had a retarded bone age and low hair zinc concentration (under 140 micrograms/g) were treated with oral zinc supplements for a year. There was a significant increase in the growth rate in the children whose hair zinc concentration increased. Growth hormone, testosterone and somatomedin C also increased after oral zinc supplementation. Data from 755 short healthy children who have attended our Growth Clinic are presented which describe their hair and serum zinc concentration at different ages. The data indicate a decline in hair zinc concentration after birth with a gradual increase at age 4-6 years, finally reaching adult normal levels after adolescence.     

Effect of the acute administration of haloperidol and pimozide on plasma GH levels in acromegaly.

In 11 untreated acromegalic patients the plasma GH levels were determined after the acute administration of bromocriptine, haloperidol, pimozide (only in 8 patients) and of placebo. A 50% or more suppression of the basal GH levels was arbitrarily defined as a positive response to bromocriptine. Five patients displayed a negative response to bromocriptine. Of these, 4 responded to both antidopaminergic drugs. We conclude that the acute administration of antidopaminergic drugs reduces the GH secretion in some bromocriptine-insensitive acromegalic patients. Therapeutical implications will require further studies.     

Effect of prolonged oral administration of TRH on plasma levels of thyrotrophin and prolactin in normal individuals and in patients with primary hypothyroidism.

Forty mg TRH/day was given orally for 3 weeks to 10 euthyroid women and 10 women with primary hypothyroidism on low replacement doses of thyroxine. Once weekly oral TRH was replaced by an iv TRH-test (0.4 mg) with measurement of serum concentration of TSH, prolactin (PRL), thyroxine (T4), triiodothyronine (T3) and cholesterol. In the normal group, mean serum T4 concentration increased after one week and remained elevated. Serum TSH concentration showed a slight tendency to decline. Maximal rise in TSH concentration after iv TRH (deltaTSH) fell from a mean of 4.0 ng/ml to 1.4 ng/ml within one week and stayed low. T3, cholesterol, PRL and deltaprl were normal and unchanged throughout. In the hypothyroid group T4, T3, cholesterol, PRL and deltaPRL were not influenced by the TRH administration. In 2 patients (with the highest serum T4 concentrations) serum TSH concentration was normal and resistant to iv TRH. Of the 8 patients with elevated TSH, basal level and deltaTSH did not change in 2 (with subnormal T4 levels and the highest TSH levels). In the other 6 (with intermediate T4 levels) basal TSH fell from a mean of 10.1 ng/ml to 4.2 ng/ml, and deltaTSH from 10.0 ng/ml to 3.3 ng/ml after three weeks. It is concluded that in addition to feed-back effect of thyroid hormones, the pituitary response to long-term administration of TRH is determined by other factors. Among these may be reduced pituitary TRH receptor capacity and the activity of the TSH producing cells.     

Effect of various oral glucose doses on plasma neutral amino acid levels

Six healthy, nonobese, fasting subjects each received, on different days 0, 6, 12.5, 25, or 50 g of glucose (Glucola) in a total volume of 100 ml. Blood was taken at intervals and assayed for plasma levels of the branched-chain amino acids (valine, isoleucine and leucine); the other major large neutral amino acids (LNAA) (methionine, phenylalanine, tyrosine and tryptophan); and, in some cases, insulin and glucose. Insulin levels were significantly elevated 30 min after consumption of 12.5, 25, or 50 g of glucose, and were higher after the 50 g dose than after 12.5 g. Changes in plasma glucose concentrations were small and did not correlate with glucose dose. Mean percent reductions of LNAA tended to exhibit dose-dependence, most clearly observed after 120 min. In some subjects as little as 6 g of glucose transiently decreased LNAA concentrations. Branched-chain amino acids were most sensitive, decreasing by 35%-41% after 50 g of glucose. Plasma tryptophan concentrations fell only by 23%, hence the ratio of plasma tryptophan to other plasma LNAA (which affects brain serotonin synthesis) increased significantly.     

Effect of omeprazole on H. pylori after two weeks of treatment.

The "clearing" effect of omeprazole 20 mg/daily on Helicobacter pylori (HP) was studied in 32 HP positive patients with duodenal ulcer (DU). Endoscopy and antral biopsies were made before and after two weeks of treatment with Omeprazole. HLO test and histology after Giemsa stain were used for the detection of HP. Fourteen of 28 (50%) initially HLO positive and 12 of 30 (40%) initially histological HP positive patients became HP negative. Nine of 23 (39%) patients, initially HP positive by both methods became HP negative. "Clearing" of HP in this particular group of patients did not have any influence on ulcer healing. It is concluded that omeprazole used for two weeks has a clearing effect on HP in a high enough percentage of patients with DU.     

Effect of acarbose administration on plasma concentrations of zinc and copper in patients with NIDDM

Acarbose reduces the intestinal absorption of dietary carbohydrate, thereby ameliorating postprandial hyperglycemia in diabetes mellitus. Dietary carbohydrate can modulate the bioavailability of some trace minerals like zinc and copper. Deficiencies in these minerals are associated with glucose intolerance. It is still unknown whether acarbose's reduction of intestinal carbohydrate absorption causes the short supply of these minerals. Thus, we investigated the changes in plasma zinc and copper levels in patients with NIDDM, after administration of acarbose for 3 months. The results showed that acarbose did not significantly affect fasting and postprandial plasma levels of these minerals, even after acarbose withdrawal. This study indicated that acarbose administration in NIDDM patients over a 3-month period does not influence plasma levels of zinc or copper.     

The effect of food composition on serum testosterone levels after oral administration of Andriol Testocaps

OBJECTIVE: Andriol Testocaps is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. DESIGN: An open-label, single-centre, four-way crossover study. With a washout period of 6-7 days, 80 mg TU was administered in the morning 5 min after consuming each of four different meals in a randomized order (A: 230 kcal, 0.6 g lipid; B: 220 kcal, 5 g lipid; C: 474 kcal, 19 g lipid; D: 837 kcal, 44 g lipid). PATIENTS: Twenty-four postmenopausal volunteers. MEASUREMENTS: Serial blood samples were collected until 24 h after dosing to determine testosterone and dihydrotestosterone (DHT) by gas chromatography-mass spectroscopy (GC-MS). RESULTS: The bioavailability of testosterone after a low-calorie meal containing 0.6 g lipid or 5 g lipid was relatively low, the area under the concentration-time curve (AUC(0-tlast)) for testosterone being 30.7 and 43.5 nmol h/l, respectively. The bioavailability of testosterone after a meal containing 19 g lipid was considerably higher (AUC(0-tlast) = 146 nmol h/l), whereas increasing the lipid content to 44 g lipid did not further increase the bioavailability of testosterone (AUC(0-tlast) = 154 nmol h/l). CONCLUSION: Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.     

Changes of serum apolipoprotein levels after oral administration of fat in human subjects

Changes of serum apolipoprotein levels were studied every hour for 6 h after the administration of 55 g butter to 8 healthy male subjects. The mean serum apo A-IV level was significantly increased at 4 h (P less than 0.05) after fat ingestion compared to the mean initial level, although no significant changes of levels in other apolipoproteins (apo A-I, A-II, B, C-II, C-III, and E) were observed. The mean apo A-IV level in the triglyceride-rich lipoprotein (TRL) fraction (d less than 1.006) increased progressively over 6 h. In all 8 subjects, the time of peak concentration of apo A-IV in TRL fraction was delayed by 1-2 h compared to that in whole serum. On the other hand, the mean apo B-48 level in the fraction reached a peak at 4 h. These results raise the possibilities that some apo A-IV, newly synthesized or already existing in intestinal cells, may be directly secreted into the venous circulation and that apo A-IV and apo B-48 may distribute differently in different sizes of chylomicron. Alternatively, the amount of each apolipoprotein synthesized may depend upon the content of ingested fat. It is suggested that apo A-IV production by intestinal cells does not appear to be regulated by the rate of fat transport, and that apo A-IV does not play an important role in chylomicron formation compared to apo B-48.