Biomedical subjects

M Hoenig

Publications and source records attributed to M Hoenig.

At least 37 records · Page 2Linked to original sources

PubMed1999

Pharmacokinetics of the antihyperglycemic agent metformin in cats.

OBJECTIVE: To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug. ANIMALS: 6 healthy adult ovariohysterectomized cats. PROCEDURE: In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography. RESULTS: Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean +/- SD) 11.5+/-4.2 hours. Metformin was distributed to a small central compartment of 0.057+/-0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12+/-0.02 and 0.37+/-0.38 L/kg. Steady-state volume of distribution was 0.55+/-0.38 L/kg. After IV administration, 84+/-14% of the dose was excreted unchanged in urine, with renal clearance of 0.13+/-0.03 L/h/kg; nonrenal clearance was negligible (0.02+/-0.02 L/kg). Mean bioavailability of orally administered metformin was 48%. CONCLUSIONS: The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction. CLINICAL RELEVANCE: On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans.

Administration, Oral↗

PubMed1997

Subnuclear localization of protein kinase C delta in beta cells.

Our laboratory has previously shown that beta cells express multiple isoforms of protein kinase C (PKC) and that some isoforms are located to multiple pools within the cell, including the cytoskeletal elements. In this study we analyzed the localization of the delta, epsilon, zeta, beta, and alpha isoforms of PKC to the nucleus. Nuclei were isolated from insulinoma beta cells and fractionated by centrifugation to give the nuclear soluble fraction, nuclear membrane fraction, and the insoluble matrix. The nuclear pellet was enriched in DNA and contained less than 5% of the total cellular nucleotidase activity. The nuclear membrane contained less than 2% of the total cellular nucleotidase activity, suggesting negligible plasma membrane contamination. Analysis of cellular fractions by immunoblotting with isoform-specific anti-PKC antibodies showed that PKC alpha, beta, zeta, and epsilon could be detected in the soluble fraction of the cell but could not be detected in the nucleus. Only PKC delta could be detected in the nucleus and was mostly present in the nuclear membrane fraction. There was light staining in the nucleocytosol and the nuclear matrix but the enzyme in the nuclear membrane represented approximately 76% of the total nuclear enzyme. Nuclear PKC delta constituted approximately 9% of the total cellular enzyme. Phorbol ester (1 microM, 15 min) increased the levels associated with the nuclear membrane approximately threefold but not to the nuclear matrix or nucleocytosol. Inhibition of PKC with MDL 29152 increased levels of preproinsulin mRNA relative to beta-actin mRNA levels, while chronic phorbol ester treatment led to a slight decrease. Taken together, these data suggest that PKC is constitutively active in the nucleus and may be important in modulating preproinsulin mRNA levels.

Animals↗

PubMed1996

Arachidonic acid-induced down-regulation of protein kinase C delta in beta-cells.

We have previously identified expression of multiple protein kinase C (PKC) isoforms in insulinoma-derived beta-cells and whole islets. Both PKC delta and PKC alpha appear to be the more abundantly expressed isoforms. In this report we studied the effects of arachidonic acid (AA) on the subcellular distribution of PKC alpha and PKC delta. AA has been reported to activate both PKC alpha and PKC delta and it is thought to be an important second messenger in beta-cells. Here we report that AA interacted with and altered beta-cell pools of PKC delta preferentially over PKC alpha. AA (100 microM) over the course of 45 min reduced cytosolic levels of PKC delta (to 40 +/- 15%, compared to time zero control) leaving membrane- and cytoskeleton-associated levels near control levels. Analysis of whole cell homogenates showed a slight down-regulation of PKC delta indicating proteolysis. The down-regulation of cytosolic PKC delta appeared to be isoform specific since cytosolic PKC alpha remained at control levels over the time course. The response was dose-dependent and negligible at concentrations below 30 microM and occurred, at least partially, in the cytosolic compartment of the cell. Indomethacin also down-regulated cytosolic PKC delta preferentially over PKC alpha possibly through accumulation of AA. These findings suggest that cytosolic PKC delta may be a downstream target of this beta-cell second messenger.

Animals↗

PubMed1996

Regulation of distinct pools of protein kinase C delta in beta cells.

Previous studies from our laboratory have demonstrated the presence of several isoforms of protein kinase C (PKC), Ca(2+)-independent and Ca(2+)-dependent, in both whole islets and tumor-derived beta cells. In the basal state, a major proportion of the isoform was found in the crude membrane fraction with smaller amounts found in both the cytosolic and cytoskeletal fractions. Whole islets showed a similar distribution of the isoform. These studies were done to analyze the effects of insulin secretagogues on the distribution of PKC delta to different cellular pools in isolated insulinoma beta cells. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), produced a transient association of PKC delta with the beta cell cytoskeleton along with sustained decreases in cytosolic enzyme and transient increases in membrane enzyme. Neither glucose nor carbachol could acutely affect the subcellular distribution of PKC delta. Oleic acid decreased the amount of the enzyme associated with the cytoskeleton and led to a sustained decrease of cytosolic enzyme and a transient increase in membrane enzyme. Oleic acid was also able to prevent the increase in cytoskeletal enzyme induced by PMA. Both oleic acid and PMA potentiated glucose-induced insulin release but oleic acid, in contrast to PMA, was unable to initiate insulin release in the presence of substimulatory concentrations of glucose. These data demonstrate that different activators of PKC may have different effects on localization of the enzyme within the cells and suggest that there are at least three apparently distinct pools of PKC delta within the beta cell which may be important in insulin secretion or other aspects of beta cell function.

Animals↗

PubMed1995

Pathophysiology of canine diabetes.

Diabetes is a fascinating, disease complex. Although much progress has been made in the last three decades to unravel the mysteries behind its multifaceted expressions, much work lies ahead. In dogs diabetes is not identified until late in the disease process. Future research might be directed at identifying early markers of the disease as an aid to improving current modes of treatment.

Animals↗

PubMed1994

Effect of protein kinase C on the plasma membrane calcium pump in purified beta cells.

The effect of protein kinase C activation on (Ca(2+)-Mg2+)-ATPase and 45Ca2+ uptake in purified plasma membranes and membrane vesicles from beta cells was examined. PKC activation was achieved by incubating cells for 10 or 30 min in 100 nM or 1 microM of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) and evident by translocation of the alpha-isoform from the cytosolic to the membrane fraction. (Ca(2+)-Mg2+)-ATPase had a Km for Ca2+ of 0.56 +/- 0.17 microM and the Vmax was 120 +/- 12 nmol/min*mg protein in membranes from cells treated with TPA, while it was 0.66 +/- 0.14 microM and 135 +/- 19 nmol/min*mg protein, respectively, in its absence. In inside-out vesicles 45Ca2+ uptake had a Km for Ca2+ of 79 +/- 19 nM and a Vmax of 1.68 +/- 0.43 nmol/min*mg protein in the presence of TPA. In the absence of TPA, the Km was 71 +/- 17 nM, and the Vmax was 1.59 +/- 0.39 nmol/min*mg protein, respectively. It is concluded that in beta cells PKC activation does not regulate (Ca(2+)-Mg2+)-ATPase activity or Ca2+ transport directly.

Animals↗

PubMed1994

Identification and subcellular characterization of protein kinase-C isoforms in insulinoma beta-cells and whole islets.

Protein kinase-C (PKC) represents a growing family of serine/threonine kinases, which include both Ca(2+)-dependent and Ca(2+)-independent members. To evaluate the expression of PKC isoforms in insulin-secreting beta-cells, purified beta-cells from a glucose-sensitive rat insulinoma were fractionated into cytosolic, crude membrane, and cytoskeletal/nucleoskeletal fractions. Protein samples from each fraction were resolved with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transblotted to nylon membranes. The blots were then analyzed with antibodies specific for the alpha, beta, gamma, epsilon, zeta, and delta isoforms. In addition, expression was analyzed in whole isolated rat islets. Expression of all except the gamma isoform was detected in the insulinoma-derived beta-cells. Expression of the alpha, beta, and epsilon isoforms was confined predominantly to the cytosolic fractions. The delta isoform could be detected in all three of the subcellular fractions, whereas the zeta isoform was present in approximately equal amounts in both the cytosolic and crude membrane fractions. The delta isoform could be eluted from the cytoskeletal/nucleoskeletal fraction with 1% Triton X-100. All of the isoforms detected in the insulinoma-derived beta-cells were also detected in whole isolated islets. It is concluded that rat insulinoma beta-cells and whole islets express numerous isoforms of PKC, including both Ca(2+)-dependent and Ca(2+)-independent isoforms, which may be important in the various signal transduction processes of insulin secretion, proinsulin biosynthesis, and insulin gene expression.

Animals↗

PubMed1994

Effects of parathyroid hormone depletion in dogs with induced renal failure.

Six parathyroidectomized (PTX) and 6 control dogs had renal mass reduced by 15/16, and were studied for effects of parathyroid hormone depletion on progression of renal failure. All PTX dogs and 4 of 6 control dogs survived until necropsy after 32 weeks. Plasma parathyroid hormone concentration was undetectable in PTX dogs throughout the study, but was greater than normal in control dogs. Serum inorganic phosphate (P) concentration was increased in PTX dogs (6.8 +/- 0.1 mg/dl) and in control dogs (7.5 +/- 0.2), but did not differ significantly (P = 0.254) between groups. Ionized blood calcium values (Ca2+) were significantly (P = 0.014) lower in PTX dogs (1.31 +/- 0.01 mmol/L) than in control dogs (1.36 +/- 0.00 mmol/L), but were more variable in PTX dogs. Values in PTX dogs were not significantly different from those in control dogs for glomerular filtration rate (P = 0.914), plasma creatinine concentration (P = 0.903), and urine protein to creatinine ratio (P = 0.756) determined at intervals during the study. Terminal glucose tolerance and plasma insulin concentrations, P tolerance, and renal P excretion did not differ between groups. Histologic comparison of kidneys removed during reduction of renal mass with kidneys removed at necropsy revealed development of lesions in both groups of dogs, and no protective effect from parathyroidectomy. Mineral analysis of aorta, brain, heart, lungs, and skeletal muscle obtained at necropsy revealed no significant difference between PTX and control groups. Renal cortical calcium concentration was significantly (P < 0.05) greater in kidneys obtained at necropsy then in kidneys obtained during nephrectomy, but PTX did not protect renal cortex from calcium deposition.

Animals↗

PubMed1993

Thyroxine and triiodothyronine distribution and metabolism in thyroxine-replaced athyreotic dogs and normal humans.

Reported parenteral L-thyroxine (T4) replacement doses (10-20 micrograms.kg-1 x day-1) are larger than T4 production rates (2.5 micrograms.kg-1 x day-1) in athyreotic dogs but not humans. Furthermore, initial volumes of 3,5,3'-triiodothyronine (T3) tracer distribution exceed those for T4 in both species. To evaluate these discrepancies, serum T4 and T3 tracer kinetic studies from T4-replaced athyreotic dogs (5 micrograms.kg-1 x day-1 sc) and euthyroid humans were analyzed in a three-pool model (rapidly and slowly equilibrating pools with serum). Dogs had lower total T4 (41%) and T3 (31%) and higher free fractions of T4 (432%) and T3 (456%) than humans. Initial T3 distribution volumes were 454% those for T4 in dogs and 149% in humans, 498% of predicted plasma volumes in dogs and 121-138% in humans. Thus plasma volumes were used as time 0 estimates for T3 data analysis. Dogs had higher fractional T4 and T3 transfer rates from serum to the rapid pools (440-451%), total T4 clearance (353%) and production rates (147%), similar total T3 clearance, but lower free T3 clearance (32%) and production rates (45%) than humans. These findings suggest: 1) higher fractional transfer rates of T4 and T3 from serum to tissues and total serum T4 clearance rates in dogs than humans relate to lower canine serum T4 and T3 binding, and 2) parenteral L-T4 replacement doses required to achieve upper-normal serum total T4 concentrations in athyreotic dogs (5 micrograms.kg-1 x day-1) correspond to T4 production rates (6.8 micrograms.kg-1 x day-1).

Adult↗

PubMed1993

Effects of orally administered prednisone on glucose tolerance and insulin secretion in clinically normal dogs.

Prednisone was administered orally for 4 weeks at a dosage of 1.1 mg/kg of body weight/d, in divided dose every 12 hours, to a group of healthy adult dogs (n = 12). Intravenous glucose tolerance testing was performed before and after the 28-day regimen in each dog, as well as in dogs of a control group (n = 6). Glucose metabolism was evaluated by measurement of preprandial plasma insulin and glucose concentrations, total insulin secretion, and fractional clearance of glucose. Mean preprandial plasma insulin and glucose concentrations were not increased after the 4-week regimen of prednisone. Total insulin secretion in response to an IV administered glucose load was not increased in treated dogs, compared with pretreatment values or with values for control dogs. The fractional clearance of glucose was also not altered in dogs given prednisone. Results indicate that anti-inflammatory doses of prednisone, given orally for 4 weeks, probably do not alter insulin sensitivity or glucose tolerance in clinically normal dogs.

Administration, Oral↗

PubMed1993

Effects of oral administration of anti-inflammatory doses of prednisone on thyroid hormone response to thyrotropin-releasing hormone and thyrotropin in clinically normal dogs.

Prednisone was given orally to 12 dogs daily for 35 days at an anti-inflammatory dosage (1.1 mg/kg of body weight in divided dose, q 12 h) to study its effect on thyroxine (T4) and triiodothyronine (T3) metabolism. Six of these dogs were surgically thyroidectomized (THX-Pred) and maintained in euthyroid status by daily SC injections of T4 to study peripheral metabolism while receiving prednisone; 6 dogs with intact thyroid gland (Pred) were given prednisone; and 6 additional dogs were given gelatin capsule vehicle as a control group (Ctrl). Baseline T4 concentration after 4 weeks of treatment was not significantly different in dogs of the THX-Pred or Pred group (mean +/- SEM, 2.58 +/- 0.28 or 3.38 +/- 0.58 micrograms/dl, respectively) vs dogs of the Ctrl group (2.12 +/- 0.30 micrograms/dl). A supranormal response of T4 to thyrotropin was observed in dogs of the Pred group, but the T4 response to thyrotropin-releasing hormone was normal. Baseline T3 concentration in dogs of both steroid-treated groups was significantly (P < 0.05) lower after 2 and 4 weeks of prednisone administration vs pretreatment values, but normalized 2 weeks after prednisone was stopped. Free T3 (FT3) and T4 (FT4) fractions and absolute FT3 and FT4 concentrations were not altered by prednisone administration. Reverse T3 (rT3) concentration in vehicle-treated Ctrl dogs (26.6 +/- 3.5 ng/dl) was not different from rT3 concentration in dogs of the THX-Pred (25.7 +/- 4.3 ng/dl) and Pred (28.9 +/- 3.8 ng/dl) groups after 4 weeks of medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Glucose tolerance and insulin secretion in spontaneously hyperthyroid cats.

Glucose tolerance and insulin secretion after administration of a glucose load were determined in 11 clinically normal cats and 15 cats with spontaneous hyperthyroidism. In six hyperthyroid cats, a glucose tolerance test was repeated after treatment with radioactive iodine (131I). All cats had similar baseline glucose concentrations. However, the cats with hyperthyroidism had a significantly decreased glucose clearance, which was worse after treatment. Hyperthyroidism also caused a marked increase in basal and glucose-stimulated insulin secretion, which was not improved with treatment. It is concluded that hyperthyroidism in cats may lead to long-lasting alterations of glucose tolerance and insulin secretion which may not be reversed by treatment.

Animals↗

PubMed1992

Na+/Ca2+ exchange in plasma membrane vesicles from a glucose-responsive insulinoma.

Plasma membrane vesicles from a glucose-responsive insulinoma exhibited properties consistent with the presence of a membrane Na+/Ca2+ exchange. The exchange was rapid, reversible, and was dependent on the external Ca2+ concentration (Km = 4.1 +/- 1.1 microM). External Na+ inhibited the uptake in a dose-dependent manner (IC50 = 15 mM). Dissipation of the Na+ gradient by 10 microM monensin decreased Na+/Ca2+ exchange from 0.74 +/- 0.17 nmoles/mg protein/s to 0.11 +/- 0.05 nmoles/mg protein/s. Exchange was not influenced by veratridine, tetrodotoxin and ouabain, or by modifiers of cAMP. No effect was seen using the calcium channel blockers, nitrendipine or nifedipine. Glucose had no direct effect on Na+/Ca2+ exchange, while glyceraldehyde, glyceraldehyde-3-phosphate and dihydroxyacetone inhibited the exchange. Na+ induced efflux of calcium was seen in Ca2+ loaded vesicles and was half maximal at [Na+] of 11.1 +/- 0.75 mM. Ca2+ efflux was dependent on [Na+], with a Hill coefficient of 2.7 +/- 0.07 indicating that activation of Ca2+ release involves a minimum of three sites. The electrogenicity of this exchange was demonstrated using the lipophilic cation tetraphenylphosphonium [( 3H]-TPP), a membrane potential sensitive probe. [3H]-TPP uptake increased transiently during Na+/Ca2+ exchange indicating that the exchange generated a membrane potential. These results show that Na+/Ca2+ exchange operates in the beta cell and may be an important regulator of intracellular free Ca2+ concentrations.

Animals↗

PubMed1992

A qualitative assay for beta cell antibodies. Preliminary results in dogs with diabetes mellitus.

Purified beta cells from a radiation-induced transplantable rat insulinoma were used to detect beta cell antibodies in serum from untreated diabetic dogs. Serum from dogs in which anti-beta cell antibodies were induced by injecting a purified beta cell suspension subcutaneously was used as positive control. Following incubation with test sera, fluorescein-labeled anti-dog immunoglobulins were used to visualize binding between the beta cells and dog gamma globulins. Nine of the 23 diabetic dogs showed a strongly positive reaction which was characterized by a ring fluorescence, three showed a weak reaction and 11 were negative, i.e. they showed diffuse fluorescence. In contrast, 14 of the 15 healthy dogs showed diffuse fluorescence and one dog showed a weakly positive reaction. Thyroid, liver and kidney cells did not elicit ring fluorescence. Although females (spayed and intact) represented the majority of the diabetic dogs, there was no correlation between sex and the occurrence of antibodies in the diabetic dogs. There was also no correlation to the age of the dogs. In conclusion, we have developed a specific test for anti-beta cell antibodies. The test is reproducible and economical to perform on a large number of samples.

Animals↗

PubMed1992

Lipid metabolism and Sarcocystis miescheriana infection in growing swine.

Sixteen 2-month-old pigs were divided into four equal groups and infected with either 500,000, 1,000,000 or 3,000,000 sporocysts of Sarcocystis miescheriana. Four pigs served as uninfected controls. Pigs were bled weekly and serum was collected beginning 14 days prior to infection and continuing until 63 days after infection. Body fat composition, as measured by the specific gravity of the carcass, was not affected by infection. There were no significant effects of infection on serum concentrations of glucose, insulin, triglycerides, and total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. A slight depression in HDL cholesterol occurred during the acute phase of infection. Tumor necrosis factor (TNF) was not detected in serum from infected swine when assayed by a cytotoxicity assay using TNF-sensitive WEHI 164 clone 13 cells. Attempts to stimulate TNF production in RAW 264.7 cells with parasitic lysates gave mixed results. This study suggests that the disruption of lipid metabolism is not the primary cause of growth retardation in growing swine infected with S. miescheriana.

Adipose Tissue↗

PubMed1992

The function of (Na(+)-K+)ATPase in the beta cell: characterization of the enzyme in a glucose-responsive insulinoma.

(Na(+)-K+)ATPase is necessary for the maintenance of the membrane potential. The activity of this enzyme was studied in purified plasma membranes from a glucose-responsive rat insulinoma. Ouabain-sensitive (Na(+)-K+)ATPase activity showed expected ATP dependency with a Km of 0.4 mM. It was also dependent on Mg2+ (Km range 70-80 microM). In the presence of Mg and ATP, half-maximal activity was obtained at a Na concentration of 30 mM and the enzyme activity increased sigmoidally with a Hill coefficient of 1.5. No direct effect on enzyme activity was observed with the insulin secretagogues glucose, fructose, glyceraldehyde, and ketoisocaproate, or with dibuturyl-cAMP and the phosphodiesterase-inhibitor isobutyl methyl xanthine. It is concluded that (Na(+)-K+)ATPase is not directly influenced by known secretagogues associated with insulin release by the beta cell.

Animals↗

PubMed1992

Effects of prednisone on thyroxine and 3,5,3'-triiodothyronine metabolism in normal dogs.

Pharmacological doses of glucocorticoids may reduce serum T4 and T3 levels in normal dogs and humans due to hypothalamic-pituitary suppression and/or altered peripheral hormone metabolism. To evaluate the chronic effects of antiinflammatory doses of glucocorticoids on peripheral thyroid hormone metabolism, serum T4 and T3 kinetic studies were performed in five thyroidectomized L-T4-replaced (5 micrograms/kg, sc, daily) normocalcemic male dogs at baseline and after 35 days of oral prednisone (0.55 mg/kg every 12 h). Data were analyzed in a three-pool model, with rapidly (liver and kidney) and slowly (muscle and skin) equilibrating pools exchanging with serum and rapid pool losses. Prednisone lowered the percent free fraction of T4 (to 70% of baseline) and total T3 (to 60%) and free T3 (to 51%) levels without significantly changing total or free T4 or percent free fraction of T3. This was associated with reduced T4 fractional transfer rates from serum rapid (to 39%) and slow (42%) pools and from rapid (to 25%) and slow pools (to 7%) to serum, and increased serum free T4 clearance rates (to 144%) as well as binding in the rapid (162%) and slow (710%) pools. Total T4 clearance and degradation rates were not significantly altered. Significant correlations included T4 binding in the rapid pool with percent free fractions of T4 (r = -0.86), T4 fractional transfer rates from rapid pool to serum with rapid pool T4 binding (r = -0.75), and fractional T4 transfer rates from slow pool to serum with slow pool T4 binding (r = -0.88). In contrast, prednisone increased fractional T3 transfer rates from serum to the slow pool (to 289%) and reduced serum (to 42%) and maximum total body degradation and production rates (to 41%) without altering total or free T3 clearance rates. Fractional T3 transfer rates from the slow pool to serum correlated with slow pool T3 binding (r = -0.84). Prednisone redistributed T4 and T3 from the serum and rapid pools to the slowly equilibrating pool. Thus, the peripheral effects of chronic antiinflammatory doses of prednisone on thyroid hormone metabolism include 1) increased T4 binding to serum carrier proteins, which may contribute to lower T4 transfer rates from serum to extravascular sites and increased extravascular T4 binding; 2) reduced fractional transfer rates of T4 from extravascular sites to serum, which may relate to increased tissue binding of T4; 3) redistribution of T4 and T3 from the serum and rapid pools to the slow pool; and 4) decreased T3 production from T4, resulting in reduced serum total and free T3 levels.

Administration, Oral↗

PubMed1992

Duration of pituitary and adrenocortical suppression after long-term administration of anti-inflammatory doses of prednisone in dogs.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P less than 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P less than 0.05) reduced and reserve function was markedly (P less than 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

Administration, Oral↗