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POSTNATAL DEVELOPMENT OF BETA-GALACTOSIDASE ACTIVITY IN THE SMALL INTESTINE OF THE RAT. EFFECT OF ADRENALECTOMY AND DIET.

1. beta-Galactosidase activity was studied in homogenates of the proximal and distal thirds of the small intestine from adult and infant rats. o-Nitrophenyl beta-d-galactoside served as the substrate. 2. Activity in suckling rats is highest in the distal part of the small intestine. 3. The pH optimum was 3.5 in the distal third of the small intestine in rats aged 5 and 15 days, whereas in the proximal third the maximum was not clearly defined. 4. Activity was higher in both thirds in newborn than in adult rats, expressed per wet wt. or per wt. of protein. In the proximal third activity continually decreases with age, whereas in the distal part there is a rise up to day 15 and then a sudden decrease. Total beta-galactosidase activity changes very little in the proximal third during postnatal development; the greatest changes occur in the distal third. 5. Adrenalectomy performed on day 15 postnatally slows down the decrease in beta-galactosidase activity, particularly in the distal part. 6. Feeding a lactose diet to infant rats from day 14 postnatally in the presence of the mother rat also slows down the decrease in beta-galactosidase activity and this is not found with a diet containing glucose and galactose instead of lactose.

Adrenalectomy↗

Incidence of Nelson's syndrome after adrenalectomy for Cushing's disease in children: results of a nationwide survey.

To establish the incidence of Nelson's syndrome in children treated with total bilateral adrenalectomy (TBA) for Cushing's disease, a survey was made of members of The Lawson Wilkins Pediatric Endocrine Society. Thirty-one patients aged 10 months to 16 years had been treated with TBA for Cushing's disease; one had been treated with ortho para prime isomer of dichlorodiphenyldichloroethane alone. Postadrenalectomy hyperpigmentation was reported in 18 patients. Sella enlargement was detected in eight patients (25%) after 1 to 5.5 years (mean, three years) post-TBA. Five of these patients have had documented pituitary adenomas to date. This incidence is higher than the adult figure of 10% to 16%.

Adolescent↗

Distinct populations of cells in the adult dentate gyrus undergo mitosis or apoptosis in response to adrenalectomy.

Granule neurons of the rat dentate gyrus are born in adulthood as well as during development. Apoptotic cell death also occurs normally in this population throughout the life of the rat. Removal of adrenal steroids results in both increased production and increased degeneration of dentate gyrus granule cells. In order to determine whether the age of a cell affects its response to adrenalectomy (ADX), the numbers of dentate gyrus cells of different ages were assessed following ADX or sham operation. Older cells, i.e., those labeled with the thymidine analog bromodeoxyuridine (BrdU) on postnatal day (P) 6, were reduced in number following ADX on P60, and some had the morphologic characteristics of degenerating cells, indicating that significant numbers of mature cells die in response to ADX. In contrast, the number of younger cells, labeled with 3H-thymidine or BrdU in adulthood, 24 hours or 2 weeks before ADX, did not decrease, suggesting that these less mature cells do not die following ADX. An increase in the number of cells that are immunoreactive for proliferating cell nuclear antigen, a marker of dividing or recently mitotic cells, indicates that immature dentate gyrus cells divide following ADX. These results suggest that following ADX, mature cells born during the 1st postnatal week die, whereas immature cells divide.

Adrenal Glands↗

Effects of adrenalectomy on Ca2+ currents and Ca2+ channel subunit mRNA expression in hippocampal CA1 neurons of young rats.

Previously it was found that the amplitude of Ca currents in CA1 hippocampal neurons increases after adrenalectomy (ADX) of young adult rats. Preliminary data suggested that this effect of ADX is age-dependent. In the present study we therefore investigated the effect of ADX on Ca currents in three age groups: rats that were 1, 3, or 6 months old. It appeared that ADX of the youngest age group resulted in a selective enhancement of sustained, high threshold Ca currents. By contrast, ADX of the oldest rats enhanced only the low threshold, transient Ca current amplitude. The age dependency of the ADX-induced effects can be explained by developmental changes in Ca current properties in the adrenally intact rats with which ADX animals were compared. Data from acutely dissociated cells, which lack most of their dendrites, suggest that the ADX-induced changes of Ca current properties are at least partly targeted at currents generated in the distal dendrites. No significant changes were observed with age or after ADX for the mRNA expression of the alpha 1D Ca channel subunit, which forms the ionpore of the sustained high threshold L-type Ca channel. We can therefore presently not exclude that the altered amplitude of Ca current with age and ADX is due to changes in ion channel function rather than in the total number of these channels.

Adrenalectomy↗

Clinical effect of aminoglutethimide, medical adrenalectomy, in treatment of 43 patients with advanced prostatic carcinoma.

The initial treatment of patients with Stage D prostatic carcinoma with orchiectomy or estrogens is successful in giving objective and subjective improvement for variable periods of time. However, after initial endocrine treatment patients generally relapse, and go on to further progression of their disease. However, a subgroup of approximately 22% of these Stage D prostatic cancer patients respond to either surgical adrenalectomy or hypophysectomy, indicating some degree of continued hormonal responsiveness. Forty-three previously castrated patients with Stage D prostatic carcinoma were treated with 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily and have been evaluated using the criteria of the National Prostatic Cancer Project. Progression of disease after initial hormonal therapy has varied from 3 to 25 months. One patient has had a complete response, and continues in remission after 290 weeks of therapy. Partial objective responses have been observed in 6 patients, and 10 patients have remained objectively stable for an average of 35 weeks in this latter group.

Adenocarcinoma↗

Leukocytosis due to adrenal metastases from malignant melanoma: reversal after bilateral adrenalectomy with long-term survival.

Leukocytosis has been noted in association with many non-hematologic malignancies in the absence of concurrent infection or metastatic involvement of bone marrow. We report a case of sustained, neutrophilic leukocytosis in a patient with disseminated malignant melanoma which reversed after bilateral adrenalectomy for adrenal metastases.

Adrenal Gland Neoplasms↗

A clinical index for selection of breast cancer patients for adrenalectomy.

Selection of patients with disseminated breast cancer for endocrine surgery has not been facilitated by sophisticated biochemical techniques. The present study was designed to produce a method of prognosis based exclusively on clinical data. Eighteen features were studied in 95 patients who underwent adrenalectomy and oophorectomy, and correlated with their degree of response to produce predictive variables. In a further group of 90 patients a prognostic score (the sum of the predictive variables) was calculated. There were 17 patients who scored less than 0 and in no case was a good response to endocrine surgery achieved. There were 40 who scored over 10, 29 of whom had a good response. The remaining 33 scored between 0 and 10 and there was no correlation between score and response. This predictive system offers significant advantages over accepted methods of clinical assessment (chi2 = 6-61, P less than 0-02). When patients with a score between 0 and 10 are excluded, its advantages are even more obvious (chi2 = 11-26, P less than 0-001). Patients who are likely to respond to endocrine surgery can be selected by clinical parameters alone, and total failure to respond can be forecast with complete accuracy. Between these two there is a third group whose response is unpredictable.

Adrenalectomy↗

Cushing's syndrome: 20 years after adrenalectomy.

The long term results (over 20 years) of our first 13 patients treated by adrenalectomy for Cushing's syndrome are described. Twelve survived operation and 5 of these died within 5 years, but thereafter the expectation of life of the treated patients was similar to that of the general population. At 20 years 7 patients were alive and 6 were well. If modern therapeutic measures to control adrenocortical function before operation has been available 20 years ago, some of the early deaths might have been prevented.

Adolescent↗

Adrenalectomy in the developing rat: does it cause reduced or increased brain myelination?

We have previously demonstrated increased myelination in adult rats that were adrenalectomized (ADX) neonatally. However, Preston and McMorris (1984) recently reported reduced myelination at Day 21 or 22 in day 14 ADX animals. The present experiment attempted to replicate Preston and McMorris' study to determine whether early adrenalectomy might be producing a transient hypomyelination prior to the hypermyelination observed at later time points. We were unable to duplicate the exact protocol of Preston and McMorris (which involved weaning at Day 18 with administration of saline and glucose drinking solutions) because of 100% mortality of our ADX rats by Day 20. However, using our standard mineralocorticoid replacement therapy which allowed the animals to remain with their mothers, all of the ADX rats survived, and we were able to assess myelination in these animals by means of standard biochemical methods. All measures showed absolutely no reduction in myelination in ADX rats compared with sham-operated controls. The discrepancy between the present results and those of Preston and McMorris are attributed, at least in part, to the early weaning procedure used by these investigators.

Adrenal Glands↗

Adrenalectomy-induced cell death in the dentate gyrus: further characterisation using TUNEL and effects of the Ginkgo biloba extract, EGb 761, and ginkgolide B.

This study investigated the potential neuroprotective effects of the Ginkgo biloba extract, EGb-761, and ginkgolide B, on adrenalectomy (ADX)-induced cell death in the dentate gyrus (DG). Adrenalectomised, sham surgery-treated, and naive controls received either EGb-761 (25, 50, or 100 mg/kg), 0.9% saline vehicle control, ginkgolide B (10 or 25 mg/kg), or a polyethylene glycol vehicle control, i.p, daily for 6 days postsurgery. Cell death in the DG was determined by in situ labelling of DNA fragments, using the TUNEL method; sections were counterstained with hematoxylin. Radioimmunoassay was used to confirm a decrease in plasma corticosterone (CORT) after ADX. TUNEL-positive granule cells were observed in the DG at 1 week, but not at 24 h, post-ADX. The rate of granule cell death at this time was highest in the suprapyramidal blade and increased in a crest tip and a rostrotemporal gradient. Whereas CORT replacement completely prevented the occurrence of TUNEL-positive granule cells, EGb-761 and ginkgolide B did not, at any of the doses used. These results suggest that these drugs may not have substantial neuroprotective effects in the ADX model of neurodegeneration.

Adrenalectomy↗

Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial memory deficits that are not reversed by chronic treatment with corticosterone or fluoxetine.

Long-term adrenalectomy (ADX) causes a nearly complete and selective loss of granule cells in the dentate gyrus (DG) of the hippocampus. Previously, learning and memory deficits have been observed following ADX-induced granule cell degeneration for tasks that require the hippocampus. Our objective here was to determine whether corticosterone (CORT) replacement and treatment with the neurogenic compound fluoxetine could reverse behavioral deficits after ADX. We trained ADX and control rats in a moving, hidden platform version of the Morris water task before chronic administration (6 weeks) of CORT and either fluoxetine or vehicle. After treatment, all rats were retested in the Morris water task. Brains were labeled for the endogenous neurogenic markers Ki67 and doublecortin. Here we provide evidence that neurogenesis persists at a normal rate in the hippocampus after long-term ADX. After 8 weeks of CORT and fluoxetine administration, ADX-fluoxetine rats did not differ significantly compared to ADX-vehicle rats receiving CORT or compared to control rats in the number of Ki67 or doublecortin labeled cells. ADX-fluoxetine rats also did not significantly differ from ADX-vehicle rats in regards to granule cell layer thickness. Our results indicate that long-term ADX is associated with impaired spatial ability in the Morris water task and that neither chronic treatment with CORT, nor with CORT and fluoxetine are capable of altering the Morris water task deficit.

Adrenalectomy↗

Time course and distribution of neuronal degeneration in the dentate gyrus of rat after adrenalectomy: a silver impregnation study.

Recently, Sloviter et al. reported that adrenalectomy (ADX) of young adult rats after 3 months led to a selective loss of granule neurons in the dentate gyrus (DG) and that this loss could be prevented by low doses of corticosterone. In the present study, the ADX-induced neuronal degeneration was investigated in Wistar rats, using a silver impregnation method for degenerating neurons. To examine the time course and distribution of the ADX-induced degeneration, young adult male rats were allowed to survive 2, 3, and 5 days and 1, 2, and 3 weeks after ADX. Argyrophilic neurons were present in the dentate granule cell layer on the second day following ADX. Three days after ADX, the number of argyrophilic granule neurons was much more abundant, and it increased gradually with longer post-ADX survival times. Argyrophilia was specifically confined to dentate granule cells and was accompanied by the occurrence of pyknotic nuclei as observed in adjacent cresyl violet-stained sections. There were significant differences between individual rats in quantity of argyrophilia. About one fifth of the ADX rats showed sporadic or no argyrophilia, in spite of plasma corticosterone levels below the detection limit (10 ng/mL). Sham-operated rats and ADX rats receiving corticosterone (10 mg/L) or dexamethasone (15 mg/L) in their drinking water did not display any argyrophilic neurons in the dentate gyrus. The distribution of the argyrophilia within the DG was highly characteristic with the highest number of degenerating cells in the hidden blade of the middle and the temporal thirds of the DG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Learning and memory after adrenalectomy-induced hippocampal dentate granule cell degeneration in the rat.

Adrenalectomy (ADX) of normal adult rats causes selective hippocampal dentate granule cell degeneration that is prevented by corticosterone. The ability to destroy this one hippocampal cell type noninvasively made it possible to address the role of the dentate granule cells in learning and memory. Four months after ADX, 31 of 45 rats failed to show obvious granule cell loss and displayed behavior in the Morris water maze that was similar to 16 sham-operated control rats and 16 ADX rats maintained on corticosterone throughout the study. Conversely, 14 of the 45 ADX rats experienced a loss of granule cells that varied from minimal to extensive. Although there were no obvious differences between groups in motoric and motivational characteristics or search strategies, ADX rats with moderate to extensive granule cell loss acquired place learning slightly slower than controls or ADX rats with minimal or no obvious cell loss. Furthermore, the ADX rats with moderate to extensive cell loss were temporarily impaired following alteration of either intramaze or extramaze cues compared to controls. In contrast, the rats with granule cell loss remembered an old place and learned a new place as quickly as controls. These results suggest that a normal complement of dentate granule cell may not be necessary for the acquisition or retention of spatial information in the Morris water maze.

Adrenalectomy↗

Hepatic gluconeogenesis and the activity of PDH in individual tissues of GTG-obese mice following adrenalectomy.

Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (PDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: 37.5 +/- 0.7 g; GTG: 44.1 +/- 0.4; p < 0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 +/- 1.6 mmol/L; GTG: 29.4 +/- 1.9 mmol/L; p < 0.05) and serum insulin levels (GTG ADX: 76 +/- 10 microU/mL; GTG: 470 +/- 63 microU/mL; p < 0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 +/- 10 nmol glucose/10(6) cells; GTG: 403 +/- 65 nmol glucose/10(6) cells; p < 0.05). ADX also significantly reduced both the glycogen (GTG ADX: 165 +/- 27 mumol/liver; GTG: 614 +/- 60 mumol/liver; p < 0.05) and fatty acid content (GTG ADX: 101 +/- 9 mg fatty acid/g liver; GTG: 404 +/- 40 mg fatty acid/g liver; p < 0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTG-obese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation. Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver.

Adrenalectomy↗

Adrenalectomy for adrenal metastasis from lung carcinoma.

In the past 3 years, five patients with lung carcinoma were found to have enlarged adrenal glands without any evidence of distant metastasis. The patients were treated with adrenalectomy. The cases are presented in order to discuss optimal methods of diagnosis and treatment for this condition.

Adrenal Gland Neoplasms↗

Effect of adrenalectomy, flutamide, and leuprolide on the growth of the Dunning rat R-3327 prostatic carcinoma.

The R-3327 prostatic tumor implanted in the male Copenhagen x Fischer F1 rat continues to grow because androgen is being supplied from an endogenous source. It follows that regimens which decrease the availability of androgen will retard the growth rate of the tumor. These experiments showed that castration, the antiandrogen flutamide, and the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide inhibited tumor growth. Adrenalectomy alone had no significant effect on tumor size and did not further retard the growth of the tumor in castrated rats. Further, under the conditions of this study, there was no significant difference in tumor growth rates between the groups of rats treated with either flutamide alone or flutamide combined with leuprolide. Total ablation of androgen may not be needed for maximal inhibition of tumor growth.

Adenocarcinoma↗

Laparoscopic nephrectomy and adrenalectomy.

Laparoscopic surgery is a rapidly evolving technique in minimally invasive surgery. In the 1970s and 1980s, the greatest advances in laparoscopy were achieved by the gynecologists. Urologist, however, have used the laparoscope for many diagnostic as well as therapeutic procedures. The initial urological procedures performed included the localization of undescended testicles. Following this, procedures such as pelvic lymphadenectomy and varix ligation became common. This paper will review the current applications of laparoscopic nephrectomy and adrenalectomy.

Adrenal Cortex Diseases↗

Effects of adrenalectomy on CART expression in the rat arcuate nucleus.

In order to test for glucocorticoid regulation of CART in the arcuate nucleus, adrenalectomies (ADX) and hormone replacements (HRs) were carried out in groups of rats. CART mRNA levels were determined by in situ hybridization and CART peptide levels by immunocytochemistry. ADX caused a lowering of CART mRNA and peptides levels in the arcuate and this was reversed by HR. These results indicate a glucocorticoid regulation of CART in the arcuate. The regulation could be direct through an action of glucocorticoid receptors or indirectly through ADX-induced changes in leptin levels. These findings suggest a role for CART in the stress response.

Adrenal Cortex↗