Adrenal Corticosteroids Research Articles

Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages.

Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate-limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2-like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage-specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy).

Effects of corticosterone on reproduction in male sprague-dawley rats

Corticosterone, the predominant circulating adrenal corticosteroid in rodents, was investigated for its effects on reproduction in male Sprague-Dawley rats. Male rats (in groups of 50, 25, and 50) were administered corticosterone at doses of 0,10, and 25 mg/kg/d, respectively, by subcutaneous injection once daily for 6 weeks; the highest dose was decreased to 20 mg/kg/d after 15 d. During the last 2 weeks of the 6-week treatment period, 25 males per group were paired with untreated females. The remaining 25 males from the 0 and 25 20 mg/kg/d groups were allowed a 6-week recovery period and, during the last 2 weeks of this period, these males were also paired with untreated females. At the end of the treatment period, the males had markedly elevated plasma corticosterone concentrations and decreased weight gain. They also produced fewer copulatory plugs than controls, which may have been secondary to observed adverse effects on the accessory sex organs (decreased weights and microscopic changes in prostate and seminal vesicles). However, no adverse effects on sperm motility, sperm count, or microscopic features of the testes were observed. Serum testosterone concentration of the high-dose males was elevated, but luteinizing hormone was unaffected. The numbers of embryonic implantation sites and live fetuses in females mated to these males were reduced. All of these effects except decreased prostate weights were reversible upon cessation of corticosterone administration. Thus, exogenous administration of corticosterone to male rats produced reversible effects on implant count and litter size of female rats mated to these males. These effects on male rat reproduction may have been secondary to reduced accessory sex organ function, which resulted in diminished secretions and fewer copulatory plugs.

Inhaled corticosteroids: Clinical relevance of safety measures

There seem to be individual, end organ, and tissue variations in responsiveness to glucocorticoids. In some children, 400-800 micrograms/day of inhaled steroid reduces cortisol excretion and short-term growth of the lower leg. These effects only become clinically relevant if the capacity of the adrenal gland to respond to stress is impaired or there is an adverse effect on bone metabolism and height velocity. Low morning plasma cortisol or reduced the cortisol excretion suggests the possibility of adrenal suppression. A stimulation test using adrenocorticotrophic hormone 500 ng is safer and more discriminating than using adrenocorticotrophic hormone 250 micrograms. For research purposes, measurement of urine cortisol metabolites over 24 hours closely approximates adrenal corticosteroid production. The dynamics of bone turnover of children are different to those of adults. Biochemical and physical studies of bone metabolism of children are hampered by a lack of age- and sex-specific normal values. Osteocalcin is probably the marker of choice for bone formation and pyridinium crosslinks for bone resorption. Bone density data in asthmatic children are limited, but so far reassuring. Knemometry is a sensitive technique for comparing the systemic absorption of different inhaled steroids, but does not relate to long-term growth. Growth velocity in asthmatic children is influenced by seasonal variation, delay in puberty, disease severity, and the use of oral steroids. These variables must be taken into account when assessing the effects of inhaled steroids. Height measurements made over a period of less than 1 year are liable to error and misinterpretation. There is no evidence that inhaled steroids, when appropriately prescribed in standard doses, have an adverse effect on long-term growth. However, children taking above-standard doses of inhaled steroids need their growth monitored using stadiometric measurements every 3-4 months by trained personnel using regularly calibrated equipment.

Immunotherapy in neuromuscular disorders: current and future strategies.

Autoimmune mechanisms have recently been implicated in the pathogenesis of an increasing number of neuromuscular diseases. Many of these diseases can be treated with immunotherapeutic agents that are currently available--often with striking success. However, lack of specificity and adverse side effects impose limits on the effectiveness of these immunosuppressive treatments. This article reviews the basic principles of autoimmunity and immune tolerance, and outlines strategies that produce (a) generalized immunosuppression; (b) "selective" immunotherapy; and (c) "antigen-specific" immunotherapy. General immunosuppressive treatments, which are the ones most commonly used in current practice, down-regulate the immune system at multiple levels in "shotgun" fashion. The agents described here include: adrenal corticosteroids, azathioprine, cyclophosphamide, chlorambucil, methotrexate, total lymphoid irradiation, plasmapheresis, and intravenous immunoglobulin. "Selective" immunotherapeutic strategies are designed to interfere with mechanisms intrinsic to the immune system. Agents that are now being used clinically, or are in advanced stages of development include: cyclosporin A, which interferes with synthesis of the cytokine interleukin 2 (IL2); IL2 toxin, which binds to IL2 receptors on activated T cells, is endocytosed, and kills the cells; and CTLA4Ig, which blocks costimulatory molecules, thus preventing full activation of T cells. We have found that combinations of the selective agents may enhance their effectiveness. "Specific" strategies are designed to inactivate or suppress antigen-specific T cells. Oral administration of autoantigens has been shown to prevent experimental autoimmune diseases specifically, but the conditions required to suppress ongoing autoimmune diseases are capricious, and depend on many factors. Finally, we describe a method that is still in the experimental stage, which is designed to modify the individual's own antigen-presenting cells so that they will target and inactivate antigen-specific T cells, and thereby turn off the specific autoimmune response. Currently available immunosuppressive methods can now be used successfully to treat many autoimmune neuromuscular diseases, and the application of selective and specific immunotherapeutic strategies promises more precise and effective treatment in the future.

The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VI. Seasonal influences on maximal electroshock and pentylenetetrazol seizure thresholds.

There is strong evidence for circadian rhythmicity in certain seizure types, whereas only a few studies have addressed the possibility of seasonal rhythms in convulsive activity. In the present experiments, seizure thresholds to different types of seizures were determined twice per month over a period of 13 months in mice under controlled environmental conditions, i.e., constant photoperiod, temperature, humidity, and food. Each group of animals was used for only one experiment, and the age of the mice used per month was the same throughout the study. Furthermore, all experiments were done at the same time in the morning to avoid circadian variation. Thresholds for the following seizure types were determined: (1) tonic hindlimb seizures induced by electrical (transauricular) stimulation; (2) myoclonic seizures induced by intravenous (i.v.) infusion of pentylenetetrazol (PTZ); (3) generalized clonic seizures in response to i.v. PTZ; and (4) tonic forelimb seizures induced by PTZ. A significant seasonality was determined for myoclonic and clonic PTZ seizure thresholds with highest thresholds between February and April and lowest thresholds between July and September. No clear seasonality was seen for chemically or electrically induced tonic seizures. Determination of plasma corticosterone did not disclose any seasonal rhythm in adrenal corticosteroid production that resembled the circannual variation in myoclonic and clonic seizure thresholds. In conclusion, our experiments suggest the existence of seasonal rhythms in PTZ seizure thresholds in laboratory animals despite standardized environmental conditions. A possible explanation for the findings may be the known seasonal alteration of the geomagnetic field which, by its effect on the pineal production of melatonin, may act as a seasonal synchronizor ("zeitgeber") in animals in the absence of other synchronizing forces, such as seasonal changes in photoperiod and ambient temperature.

Laparoscopic Adrenalectomy

Adrenal pathology requiring surgical intervention is relatively uncommon. Nevertheless, there are a number of conditions that warrant such consideration. Most surgically correctable diseases of the adrenal glands are associated with excess production of adrenal corticosteroids or catecholamines by an adrenal tumor. Classic open approaches toward adrenalectomy in the past have included an anterior, transabdominal, or posterior route. Laparoscopic adrenalectomy offers the advantages of excellent exposure through minimally damaging portals. This results in an expected very benign postoperative course. It has now been almost 4 years since the first reported laparoscopic adrenalectomy. Since then, numerous small series have been reported and experienced laparoscopic surgeons have proven the merits of a laparoscopic approach to adrenalectomy. This reviews the current state of the art and offers descriptions of selected approaches to both the right and left adrenal glands.

Preprothyrotropin-releasing hormone-(178-199) does not inhibit corticotropin release.

Pituitary ACTH synthesis and secretion are positively regulated by hypothalamic factors and negatively regulated by adrenal corticosteroids. Negative hypothalamic regulation of pituitary ACTH synthesis and secretion has been postulated, but not proved. The search for a hypothalamic corticotropin release-inhibiting factor has recently focused on peptides derived from the prepro-TRH precursor of TRH. One of the peptides, prepro-TRH-(178-199), was reported to suppress basal and stimulated ACTH release. We examined the effects of prepro-TRH-(178-199) alone and in combination with CRH and corticosterone, two known physiologic regulators of ACTH secretion. Prepro-TRH-(178-199) had no effect on basal, stimulated, or attenuated ACTH release from cells that responded normally to CRH and/or corticosterone. These results indicate that prepro-TRH-(178-199) is not a corticotropin release-inhibiting factor.

Divergent prolactin and pituitary-adrenal activity in rats selectively bred for different dopamine responsiveness.

The present study explores the significance of brain dopamine phenotype for individual variation in the neuroendocrine stress response of the rat. For this purpose, we used two Wistar rat lines previously selected for high or low responsiveness of the dopamine system to apomorphine using the gnawing response as the selection criterion. Systemic administration of the drug evoked in apomorphine-susceptible (apo-sus) rats a vigorous gnawing response, whereas apomorphine-unsusceptible (apo-unsus) rats did not gnaw under these conditions. These two rat lines represent individuals displaying extreme differences in gnawing behavior that otherwise coexist in a normal Wistar population. In this study basal and stress-induced hypothalamic-pituitary-adrenal activity and PRL release were measured in chronically cannulated, freely moving rats that endured a conditioned emotional response. Tyrosine hydroxylase messenger RNA (mRNA), corticosteroid receptor mRNA, and in vivo retention of [3H]corticosterone were measured in rat brain sections using in situ hybridization and in vivo autoradiography. The result show that 1) apo-sus rats had a markedly reduced PRL response to stress compared to apo-unsus animals, whereas basal levels were not significantly different. A12 dopaminergic neurons in the arcuate nucleus expressed significantly higher levels of tyrosine hydroxylase mRNA in apo-sus rats, suggesting that the reduced stress-induced PRL release could be due to an increased inhibitory control by dopaminergic neurons; 2) in apo-sus rats, stress resulted in a sustained elevation of ACTH and free corticosterone levels, whereas the total corticosterone levels were not different between the two rat lines; 3) under basal morning conditions, apo-sus rats had significantly higher plasma ACTH, but, in contrast, lower free corticosterone than apo-unsus rats; total plasma corticosterone levels were not different; 4) the basal evening ACTH level was elevated in apo-sus rats; after removal of the adrenals in the morning, this increased ACTH level in apo-sus rats persisted into the afternoon 6 h postadrenalectomy; and 5) hippocampal mineralocorticoid (MR), but not glucocorticoid (GR), receptor capacity for the ligand comparable between the groups; the MR of apo-sus rats displayed an increased retention of [3H]corticosterone in all hippocampal cell fields measured 24 h adrenalectomy; MR and GR mRNA in hippocampus as well as GR mRNA in the paraventricular nucleus were not significantly different in the two rat lines. In conclusion, the data suggest a common genetic background for individual variation in stress responsiveness and dopamine phenotype. High dopamine reactivity is linked to a reduced PRL and an increased ACTH response after stress. These high dopamine responders display a hyporesponsive adrenal cortex and corticosteroid feedback resistance associated with altered brain corticosteroid receptor properties.

Glucocorticoids Block Protein Kinase A Inhibition of Calcium-activated Potassium Channels

Adrenal corticosteroids have well known and profound effects on neurons and neuroendocrine cells, but the underlying cellular mechanisms are poorly understood. The present study analyzed membrane currents and ACTH release in AtT20 mouse pituitary corticotrope tumor cells. Patch-clamp analysis revealed a significant and selective inhibition of calcium-activated (BK-type) potassium channels upon activation of protein kinase A by corticotropin-releasing factor or 8-chlorophenylthio-cAMP. The synthetic glucocorticoid dexamethasone had no effect on potassium currents evoked by depolarization but prevented the inhibitory effect of protein kinase A activators. The action of dexamethasone had the hallmarks of protein induction, i.e. a lag time and sensitivity to inhibitors of DNA transcription and mRNA translation. In parallel, the specific BK channel blocker iberiotoxin abolished early glucocorticoid inhibition of corticotropin-releasing factor-stimulated ACTH secretion. In summary, the present data show that glucocorticoid-induced proteins render BK-type channels resistant to inhibition by protein kinase A and that this action of the steroid is pivotal for its early inhibitory effect on the secretion of ACTH.

Differential effects of glucocorticoids on human auditory perception

It is assumed that glucocorticoids and mineralocorticoids, the hormones produced by the adrenal cortex, act as modulators of central nervous functions in addition to their well known role in endocrine stress responses. More specifically, it has been suggested that adrenal corticoids cause changes in sensory thresholds. In two double-blind crossover studies we evaluated auditory perception in healthy volunteers after treatment with hydrocortisone, dexamethasone, and the respective placebos. Stapedial reflexes, pure tone and speech audiograms, and brainstem electric response audiometry served as the dependent variables. As circadian changes in the density and occupancy of the brain corticosteroid receptors have been postulated, we performed Study I in the morning and Study II in the evening. Treatment effects clearly varied with time of day. A differential effect of the two corticoids occurred on contralateral stapedial reflexes. These results parallel results obtained with gustatory stimuli, and suggest that glucocorticoids modulate sensory perception across modalities.

Studies on fatigue of night duty workers at a newspaper office.

Fatigue of night duty workers in different divisions of a newspaper office was investigated by physiological methods such as the Blinker, Flicker and grip methods. The relationship between fatigue and hematological parameters such as hemoglobin (Hb), the hematocrit (Ht), serum-free amino acid levels, and indices of liver function such as the GOT and GPT levels were also examined. The composing and press room workers mainly complained of the subjective symptom of muscle fatigue, while workers in the photo-engraving and editorial departments mainly complained of mental fatigue. The overall rate of fatigue in the newspaper office was about 38.1%, but varied from one division to another, being especially high in the photo-engraving and editorial departments. The subjects with fatigue had low levels of serum GOT and GPT and high levels of serum-gluconeogenic amino acids, such as aspartic acid, glutamic acid, prolin, glycine, and alanine. These altered levels of serum-free amino acids and GOT and GPT seemed to be due to increased secretion of adrenal corticoid hormone caused by the stress of fatigue.

Influence of 17- alpha-estradiol on catecholamine secretion from the perfused rat adrenal gland.

Objectives:It has been known that adrenal corticosteroids influence the expression of adrenomedullary catecholamine-synthetizing enzymes and also suppress the emission of axonal-like processes in cultured chromaffin cells. In the present study, it was attempted to investigate the effect of 17-α-estradiol on catecholamine (CA) secretion evoked by acetylcholine(ACh), DMPP, McN-A-343. excess K+ and Bay-K-8644 from the isolated perfused rat adrenal gland.Methods:Mature male Sprague-Dawley rats were anesthetized with ether. The adrenal gland was isolated by the method of WaKade. A cannula used for perfusion of the adrenal gland was inserted Into the distal end of the renal vein. The adrenal gland, along with ligated blood vessels and the cannula, was carefully removed from the animal and placed on a platform of a leucite chamber.Results:The perfusion of 17-α-estradiol (1–100 uM) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.32 mM). DMPP (100 uM for 2 min). McN-A-343 (100 uM for 2 min) and Bay-K-8644 (10 uM for 4 min). while it did not affect the CA secretory effect of high K+ (56 mM), Also, in the presence of 17-β-estradiol, CA secretion of ACh, DMPP and McN-A-343, without any effect on excess K+-evoked CA sectretion was depressed. However, in adrenal glands pre-loaded with 17-α-estradiol (10 uM) plus tamoxifen (2 uM). which is known to be a selective antagonist of estrogen receptors (for 20 min), CA secretory responses evoked by ACh, DMPP and McN-A-343 were considerably recovered as compared to that of 17-α-estradiol only, but excess K+-induced CA secretion was not affected. However, pre-treatment with 17-α-estradiol in the presence of meclopramide(dopaminergic antagonist) did not affect the secretory effect of CA evoked by ACh, DMPP, McN-A-343 and high potassium.Conclusions:These results suggest that 17-α-estradiol causes the marked inhibition of CA secretion evoked by cholinergic receptor stimulation, but not that by excess K+, indicating strongly that this effect may be mediated by inhibiting the influx of extracellular calcium into the rat adrenomedullary chromaffin cells through the activation of inhibitory estrogen receptors, and it also plays a modulatory role in regulating CA secretion.

Imaging in candidiasis

ANDIDA IS A ubiquitous fungus commonly found in the normal flora of the mouth, oropharynx, intestines, vagina, and skin. The mouth, esophagus, lungs, and urinary tract are frequent sites of local infections. 1 Systematic candidiasis is defined as an invasive infection involving the parenchyma of two or more visceral organs excluding the mucosa of the gastrointestinal, respiratory, or genitourinary tracts. 2 Most infections are caused by Candida albicans and Candida tropicalis. 3 The review will emphasize hematogenously disseminated disease. Hematogenously disseminated candidiasis most often occurs in patients who are immunocompromised or debilitated, have been subjected to major trauma, or undergone complicated surgery, especially of the gastrointestinal tract? About half of the patients have a prior or concurrent bacterial infection usually resulting in tissue damage. 5 About 90% of patients are receiving broad-spectrum antibacterial antibiotics and about half are receiving parenteral nutrition. Candida infection is unlikely to occur in patients who are not already colonized by the organism. 6 There are no characteristic signs or symptoms to suggest the diagnosis of disseminated candidiasis. Patients typically present with persistent or recurrent fever despite broad-spectrum antibacterial therapy. Pneumonia, deteriorating liver or renal function, and general deterioration may occur. Adrenal corticosteroid therapy may mask fever. Some patients present with symptoms suggestive of endotoxin shock. 7 Ocular involvement is present in from 5% to 45% of patients, s It is rare in neutropenic patients. Characteristic skin lesions have been described in about 10% of patients. 9 The lesions are discrete, nontender, firm, raised nodules

Significance of adrenal corticosteroid secretion for the food restriction-induced enhancement of alcohol drinking in the rat

Male Wistar rats with continuous access to 6% ethanol solution and water in their home cages were subjected to food restriction (FR). Reduction of body weight to 80% of normal was associated with a significant increase in ethanol drinking. It is known that the stress of FR gives rise to increased corticosterone secretion, and in line with these findings it was found that the weight of the thymus (whose size is inversely related to corticosterone levels) was reduced to 55% of normal in the present FR rats. Two subsequent experiments indicated that this adrenal activation contributed to the FR-induced enhancement of alcohol drinking. Firstly, adrenalectomized rats showed no evidence of enhanced alcohol drinking during food restriction, suggesting that adrenal corticosterone hypersecretion contributes to the enhanced ethanol consumption during FR. Secondly, treatment of FR rats with the enzyme inhibitor cyanoketone, which blocks stress-induced but not basal corticosterone secretion, at least partly prevented the FR-induced increase in ethanol drinking. These results add further evidence that sustained exposure to corticosterone facilitates ethanol consumption in the rat.

Regular β-Adrenergic Agonists

Some 30 years ago we found that mortality from asthma was rising. There was no obvious reason for this and therefore a large number of investigations were carried out all over the world. No clear cut cause emerged and thus iatrogenesis was considered as one of the possible causes. β-Agonist sympathominetics in aerosol form and adrenal corticosteroids were the two new agents introduced at about the same time. Suspicion should logically have fallen on these two but only β-agonists were criticized. Apart from stray voices 1 Govindaraj M Deaths from asthma [letter]. BMJ. 1968; I: 515 Crossref Scopus (2) Google Scholar , 2 Ziment I β-agonists and bronchial asthma [letter]. Chest. 1994; 106: 323-324 Google Scholar most looked on steroids as life saving agents and thus beyond reapproach. After much debate and therapeutic correctives, the mortality from asthma has by and large, remained unacceptably high.

Corticosteroid Hormones: Endocrine Messengers in the Brain

Adrenal corticosteroid hormones reach many organs including the brain where they exert persistent actions on neuronal excitability. Normally, steroid actions will maintain the integrity of neuronal networks, yet chronically decreased or enhanced corticosteroid levels can disrupt networks and enhance susceptibility to neurodegeneration.

Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice.

The plasma cholesteryl ester transfer protein (CETP) mediates the exchange of HDL cholesteryl esters (CE) and VLDL triglycerides leading to catabolism of HDL. There is some evidence that HDL ameliorates the toxicity of LPS, and LPS is known to influence several enzymes affecting HDL metabolism. Therefore, the effects of LPS on CETP and plasma lipoproteins were examined in human CETP transgenic mice. Administration of LPS to mice expressing a CETP transgene linked to its natural flanking sequences (NFR-CETP Tg) resulted in a rapid marked decrease in hepatic CETP mRNA and plasma CETP concentration. Corticosteroid injection produced a similar decrease in hepatic CETP mRNA and adrenalectomy abolished this response to LPS. LPS caused disproportionate reductions in plasma CETP activity compared to mass, and was found to be a potent inhibitor of CETP activity when added directly to plasma. LPS was injected into mice expressing (A) a human apoA-I transgene, (B) apoA-I and NFR-CETP transgenes, or (C) apoA-I and LPS-inducible metallothionein promoter-driven CETP transgenes, producing (A) minimal changes in HDL cholesterol, (B) decreased plasma CETP and increased HDL cholesterol, and (C) increased plasma CETP and decreased HDL cholesterol. Thus, LPS administration produces a profound decrease in hepatic CETP mRNA, primarily as a result of adrenal corticosteroid release. The decrease in plasma CETP activity after LPS administration may reflect both this effect as well as a direct interaction between CETP and LPS. The decrease of CETP in response to LPS has major effects on HDL levels, and may represent an adaptive response to preserve or increase HDL and thereby modify the response to LPS.

Acute non-pathologic blood pressure changes associated with buspirone use in psychiatric inpatients

1. 1. Buspirone is one member of a class of novel azapirone drugs recently introduced to treat anxiety, a disorder frequently associated with increased adrenal corticosteroid secretion in man. 2. 2. The effects of buspirone on systolic and diastolic blood pressure were studied following acute administration to 20 psychiatric inpatients with a variety of diagnoses. The findings indicated that by the second day of buspirone therapy, non-pathologic increases and decreases in blood pressure could be detected. The direction of these changes appeared to be associated with diagnostic class rather than age, dose, or coexisting medication. 3. 3. The majority of the changes in blood pressure during the initial stage of buspirone therapy were transient, reverting to baseline by the fourth day of buspirone therapy.

Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids

Leukocyte adhesion is a key factor in the pathogenesis of organ injury following a variety of stimuli. In this study we have addressed the role of leukocyte adhesion in hypertensives as a risk factor for organ injury. In the spontaneously hypertensive rat (SHR), the number of circulating leukocytes and their level of activation are significantly increased compared with its normotensive control, the Wistar-Kyoto rat (WKY). We have demonstrated that elevated levels of glucocorticoid in SHR suppress P-selectin-mediated leukocyte-endothelial interaction in the microcirculation. It is possible that the disturbance in leukocyte-endothelial interactions may result in an elevated number of leukocytes in the circulation. The aim of the present study was to investigate the contribution of the adrenal glands to the disturbance in leukocyte behavior in SHR by subjecting the animals to bilateral adrenalectomy and investigating the effect of hydrocortisone. In addition, we have studied by immunohistochemistry the expression of the endothelial adhesion molecule, P-selectin, in response to histamine in the mesenteric venules of normal and adrenalectomized SHR and WKY. The elevated blood pressure, above-normal leukocyte counts, and elevated number of activated neutrophils (nitroblue tetrazolium test) in SHR were blunted after adrenalectomy. The blunted histamine-induced leukocyte-endothelial interaction in the mesenteric venules of SHR was restored after adrenalectomy. Treatment with hydrocortisone significantly attenuated the elevated leukocyte adhesion in the adrenalectomized SHR as well as in WKY. The suppressed P-selectin expression in SHR mesentery was restored after adrenalectomy. In conclusion, the subnormal leukocyte-endothelial interaction in response to an inflammatory stimulation in SHR is abolished after adrenalectomy, suggesting a relationship between the altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensives.

悪性リンパ腫を合併したウエゲナー肉芽腫症

Malignant lymphoma of the thyroid developed following supportive immunosuppressive therapy with adrenal corticosteroids and immuno-suppressive drugs for Wegener's granulomatosis. Wegener's granulomatosis was diagnosed in a 58-year-old male who complained of left cheek pain and swelling, epistaxis and visual disturbance. He was treated with prednisolone, azathioprine and cyclophosphamide. Four and a half years later, non-Hodgkin's lymphoma of the thyroid was diagnosed. Autoimmune disease, immuno-suppressive therapy and other factors thought to be related to immune disturbances have been reported in association with malignancies. We discuss the association of immune disturbances, immuno-suppressive therapy and carcinogenesis.