Effect of cortisol and ACTH on corticosteroid-suppressed peripheral blood natural killer cells from healthy volunteers and patients with Crohn's disease

Recently, we have shown that administration of adrenocorticotropic hormone (ACTH) to corticosteroid-treated Crohn's disease (CD) patients increased the peripheral blood natural killer (NK) cell activity which was suppressed by the corticosteroids. To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers and corticosteroid-treated CD patients. Incubation of peripheral blood mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay caused a dose-dependent inhibition of NK cell activity by the three corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting concentrations also showed a significant inhibiting effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did not restore the corticosteroid-induced suppression of NK cell activity. The increase of the budesonide- or prednisolone-suppressed NK cell activity after in vivo administration of ACTH to the CD patients is therefore probably not a direct effect of cortisol or ACTH. Presumably other factors like cytokines and/or neurohormones must be involved in the in vivo interaction between corticosteroids, ACTH, and NK cells.     

Carbon dioxide efflux accompanies release of fertilization acid from sea urchin eggs

"Fertilization acid" is released from sea urchin eggs upon fertilization and decreases the pH of the surrounding seawater. In bicarbonate-free artificial seawater flushed with nitrogen gas, the pH shift still occurs but returns to the original value in a few minutes, suggesting that the released acid volatile. A likely candidate for a volatile acid is carbon dioxide released from the eggs. Therefore, the total CO2 content of seawater was measured pre- and post-fertilization and was found to be correlated stoichiometrically with released proton equivalents, leading to the conclusion that fertilization acid is largely carbon dioxide. Manometric analysis of cell extracts and ashed eggs suggest that the carbon dioxide may be stored in the unfertilized egg as an inorganic carbonate.     

A chronobiological approach to circulating levels of renin, angiotensin-converting enzyme, aldosterone, ACTH, and cortisol in Addison's disease

This study deals with a chronobiological approach to the circadian rhythm of the renin-angiotensin-aldosterone system (RAAS) and the ACTH-cortisol axis (ACA) in patients with Addison's disease (PAD). The aim is to explore the mechanism(s) for which the circadian rhythmicity of the RAAS and ACA takes place. The study has shown that both the RAAS and ACA are devoid of a circadian rhythm in PAD. The lack of rhythmicity for renin and ACTH provides indirect evidence that their rhythmic secretion is in some way related to the circadian oscillation of aldosterone and cortisol. This implies a new concept: a positive feedback may be included among the mechanisms which chronoregulate the RAAS and ACA.     

Effects of naloxone on beta-endorphin and cortisol release in sepsis

This study assessed sepsis-induced changes in the contents of calpain and cathepsin B in rat soleus muscle. Sepsis was induced in rats by intra-abdominally implanting fecal pellets containing Escherichia coil and Bacteroides fragilis. Intact soleus muscles were isolated from non-operated control rats, and from rats sacrificed 1 and 2 days after they were implanted with bacteria-free (sterile implanted) or bacteria-laden (septic implanted) pellets. Western blot analyses of muscle homogenates were performed to identify and quantitate these proteinases using specific antibodies. No significant differences in cathepsin B contents were observed between the septic and nonseptic animals on days 1 and 2, post-implantation. Among the three distinct bands recognized by anti-calpain, two prominent bands of 80 and 76 kDa, representing calpain subunits, did not seem to be altered in septic rats compared to the nonseptic groups. The content of the 45-kDa subunit decreased in both the septic and sterile groups compared with non-operated control. These results along with our previous observations suggest that although Gram-negative sepsis does not appear to have an effect on Ca2(+)-insensitive lysosomal cathepsin B content or activity, it upregulates the activity of the Ca2(+)-dependent calpain but not its content in the skeletal muscle during sepsis.     

Profiles of daily secretion of ACTH, beta-endorphins and cortisol in patients after minor craniocerebral trauma

In 12 men aged 20-25 men who had minor craniocerebral trauma the profiles of daily secretion of ACTH, beta-endorphin and cortisol were studied. The studies were carried out on the second day after the trauma. Plasma concentrations of the hormones were determined on 8.00, 12.00, 17.00 and 22.00 hours. Statistically significantly increased, in relation to healthy persons, (p < 0.01) values of plasma hormone concentration were found at all time points. In 50% of the patients (six cases) a disturbance was found of the profile of daily secretion of ACTH and beta-endorphin. The disturbance of the profile of cortisol secretion was found only in one patient.     

Rate of decline of cortisol concentrations in ovarian follicles following ACTH treatment in the sow

Three milliliters of blood from the present commercially produced heartwater infective blood vaccine (Ball3 stock) was experimentally tested in sheep and cattle for infectivity and efficacy. Results obtained for this vaccine dose were statistically not different from results for the prescribed 5 ml vaccine dose.     

Effect of stimulus intensity on prolactin and cortisol release induced by unilateral electroconvulsive therapy

The corneal wound-healing properties of fibronectin (FN) and a fibronectin hydrolysate (FNH) have been evaluated in comparison with commonly used drugs. Nonpenetrating bilateral surgical keratectomy was performed in male albino rabbits. The left eye was treated with the active product, whereas the right eye served as a control (vehicle). The healing area was measured by planimetry after fluorescein staining at 0, 24, 48, and 72 h after keratectomy. Histological and immunohistochemical analysis of the healing process was also performed. Results were as follows: (a) Nandrolone (p < 0.005) and asiaticoside (p < 0.001), both at 10 mg/ml, in eyedrops delayed the healing process. (b) An ointment containing vitamin A and amino acids also delayed the process but at the limit of statistical significance (p = 0.055). (c) FNH (20-80 mg prot/ml) significantly improved the quality and shortened the time of the healing process at 60 mg prot/ml and above. (d) Human FN (100-800 micrograms/ml) did not affect the healing process. Immunohistochemical analysis demonstrated that FNH accelerated the appearance of endogenous FN in the damaged cornea earlier than in the control eyes. It is concluded that FNH may be useful in the management of corneal wounds, whereas the effectiveness of FN is doubtful.     

Hormonal (ACTH, cortisol, beta-endorphin, and met-enkephalin) and cardiovascular responses to hyperthermic stress in chronic alcoholics

Chronic alcohol drinking causes profound alterations in hypothalamic-pituitary function. In the present study, endocrine [corticotropin (ACTH), beta-endorphin, cortisol, and met-enkephalin] and cardiovascular (blood pressure) changes in response to hyperthermic stress (sauna at 90 degrees C for 30 min) were evaluated in 25 normal men (25 to 50 years old) and in 48 male alcoholic subjects (34 to 56 years old) after 5 weeks of abstinence. Significantly lower increments in systolic blood pressure were observed in alcoholics than in control subjects. Furthermore, alcoholics showed lower ACTH, beta-endorphin, and cortisol increments in response to sauna than normal controls. In contrast, sauna-induced hyperthermia did not change significantly the circulating met-enkephalin levels in either normal controls or chronic alcoholics. These data suggest that an impairment in the adaptive response to stress affects alcoholic men even after a few weeks of abstinence from alcohol.     

Normal final height and apparent cure after pituitary irradiation for Cushing''s disease in childhood: long-term follow-up of anterior pituitary function

1. We evaluated the effects of ethanol on (Na + K)-ATPase activity and cAMP response to vasopressin in native and cultured rat papillary collecting duct (PCD) cells. 2. A significant increase in (Na + K)-ATPase and Mg(2+)-ATPase activities was found in PCD cells either isolated from chronic ethanol-fed rats or cultured in the presence of ethanol. 3. Acute treatment with ethanol resulted in a biphasic effect on the activity of (Na + K)-ATPase, which was enhanced below 1% ethanol and inhibited at higher concentrations. 4. Chronic ethanol treatment did not change the cAMP response of PCD cells to vasopressin. Acutely, in turn, this response was enhanced by ethanol per se. 5. It is suggested that the antinatriuretic effect of ethanol could be at least in part mediated by a (Na + K)-ATPase enhancement in PCD cells. Acutely, ethanol could normalize water balance by its peripheral effects on distal nephron.     

Time course of changes in free thyroid indices, rT3, TSH, cortisol and ACTH following exposure to sulfur mustard

In order to evaluate the time course of changes in serum concentration of thyroid hormones, cortisol and ACTH in patients exposed to chemical weapons containing sulfur mustard, we measured serum concentrations of hormones on the first, third and fifth week following injury in 13 soldiers and compared them to the results obtained from 34 control men. Free T4 and T3 indices were decreased and rT3, cortisol and ACTH were increased in the first week following exposure. There was a subnormal TSH response to TRH in 2 of 3 men tested. Except for an increase in FT4I and a decrease in TSH by the third week, and a steady decline in serum cortisol, serum hormone concentrations were unchanged until the fifth week after injury. The decline in serum cortisol occurred despite a constant increase in serum ACTH. By the fifth week only 1 of 13 men had serum cortisol levels > 10 micrograms/dl. We conclude that exposure to chemical weapons containing sulfur mustard results in alterations in serum concentrations of thyroid and adrenal hormones and ACTH, resembling changes seen in burn trauma. Some evidence of direct effects of mustard on endocrine glands exist.     

Plasma atrial natriuretic factor levels in the inferior petrosal sinus blood of patients with Cushing''s disease before and after corticotropin-releasing hormone administration

OBJECTIVE: To study the effect of postoperative thyroxine on the volume of the thyroid remnant after lobectomy for benign nontoxic goitre. DESIGN: Prospective, randomised study. SETTING: University hospital, Sweden. SUBJECTS: 50 consecutive patients who underwent lobectomy for benign non-toxic goitre. INTERVENTIONS: Patients were randomised postoperatively to take thyroxine 0.1 mg or placebo daily. MAIN OUTCOME MEASURES: The median volume of the remaining thyroid lobe measured by ultrasound. Serum concentrations of thyroxine, triiodothyronine (T3) and thyroid stimulating hormone (TSH) were measured preoperatively and 1, 3, 6, 12 months postoperatively. RESULTS: The median volume of the remaining lobe had increased significantly compared with preoperatively by 1 month postoperatively by 30% in the thyroxine group and 25% in the placebo group (p < 0.01). The difference between the groups was not significant. After the first month the volume did not change significantly. In the thyroxine group, the TSH concentration was unchanged and the thyroxine concentration increased significantly throughout the study. In the placebo group there was a significant increase in TSH concentration and a significant decrease in that of thyroxine at all follow-up examinations. CONCLUSIONS: There is a significant increase in the volume of the remaining thyroid 1 month after lobectomy that persisted throughout the first year. Thyroxine given in a dose that kept the serum TSH concentration at the same level as preoperatively did not seem to influence volume changes; consequently we consider that these are caused by factors other than TSH.     

Effect of pulsatile oxytocin administration to the pregnant ewe in the last third of gestation on fetal ACTH and cortisol response to acute hypoxemia

OBJECTIVE: The aim of this study was to examine the effect of increased myometrial contractility throughout the last third of pregnancy on the ovine fetal response to short-term hypoxemia. METHODS: Oxytocin (600 microU/kg/minute, n = 5) or saline (n = 7) was infused for 5 minutes every 20 minutes into the maternal jugular vein starting at 95-99 days of gestation and continuing throughout the last third of gestation. Fetuses were subjected to a hypoxemic challenge (1 hour) at 131 days of gestation while fetal plasma ACTH and cortisol levels and nuchal muscle electromyogram activity were monitored. RESULTS: The fetal plasma ACTH concentration before and during the hypoxemic challenge was similar in the control and oxytocin groups. The fetal plasma cortisol concentration in the oxytocin group was significantly lower before and during the hypoxemia than in the controls. During hypoxemia, fetal nuchal muscle activity was significantly reduced only in the control group. CONCLUSION: Increased myometrial contracture frequency throughout the last third of pregnancy alters both the neuroendocrine and behavioral responses of fetal sheep to short-term hypoxemia.     

Greater relative impairment of object recognition than of visuospatial abilities in Alzheimer's disease.

Histological investigation in Alzheimer's disease (AD) has indicated that the concentration of neurofibrillary tangles in inferotemporal cortex (IT) is greater than that found in posterior parietal cortex (PPC). Researchers hypothesized that the relative degree of impairment of visual function subserved by each of these cortical areas should reflect the disproportionate distribution of neuropathological changes. Eleven AD patients and 16 elderly controls received 8 tests of visual function, 4 of which have been shown previously to be selectively affected by IT lesions and 4 that are selective for PPC lesions. AD patients were significantly impaired on all 8 tests, but multivariate analysis indicated a relatively greater impairment on tests of IT function. The greater impairment of visual function mediated by IT relative to function mediated by PPC is consistent with differential degradation of the respective cortical areas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease

OBJECTIVE: This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional, between-subject design, using an age-regression model. SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores. RESULTS: The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance. CONCLUSIONS: This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.     

Vascular endothelium and smooth muscle remodeling accompanies hypertrophy of intestinal arterioles in streptozotocin diabetic rats

The purpose of this study was to document alterations in endothelial and smooth muscle cell morphology of first- and second-order intestinal arterioles after 6 months of streptozotocin-induced diabetes. Both light and scanning electron microscopic techniques were used to quantitate the changes in the microvasculature. After rendering the first- and second-order intestinal arterioles passive and processing the vessels, it was determined that these microvessels were significantly dilated in the diabetic animals. Further examination revealed that in the diabetic animals, the cross-sectional area of the endothelial layer was increased in both 1A and 2A vessels, and the smooth muscle layer cross-sectional area was significantly increased in 1A vessels. Individual smooth muscle cells were significantly increased in width in the diabetic animals, but not in length. These data suggest that in this model of diabetes in rats, intestinal arteriolar hypertrophy was accompanied by significant remodeling of the arteriolar wall.     

Activation of separate calcium and A-kinase-dependent pathways by ACTH

Although cAMP has long been regarded as the primary intracellular messenger for ACTH-stimulated cortisol secretion, a requirement for Ca2+ is well established. However, a specific mechanism which couples ACTH receptor activation to increased intracellular calcium concentration in the adrenal cortical cell has not been elucidated. Here, we present evidence for a specific model in which ACTH at picomolar concentrations induces cAMP which acts through kinase-dependent and independent pathways to stimulate cortisol secretion. Along one of these pathways, cAMP acts directly to depolarize cells by inhibition of a specific non-inactivating K+ channel (I(AC)). This model provides a specific mechanism whereby cAMP-mediated inhibition of I(AC) is tightly coupled to depolarization-dependent Ca2+ entry and cortisol secretion. Ca2+ and cAMP are dual second messengers in the ACTH signalling pathway that are linked through I(AC) K+ channels.     

Double adenomas with different pathological and hormonal features in the left adrenal gland of a patient with Cushing''s syndrome

A simple method is presented for projecting the conformation of extended secondary structure elements of peptides and proteins that extend over four C alpha atoms onto a simple two-dimensional surface. A new set of two degrees of freedom is defined, a pseudodihedral involving four sequential C alpha atoms, as well as the triple scalar product for the vectors describing the orientation of the three intervening peptide groups. The method provides a reduction in dimensionality, from the usual combination of multiple phi,psi pairs to a single pair, yielding valuable information concerning the structure and dynamics of these important elements. The new two-dimensional surface is explored by reference to 63 selected protein crystal structures together with a comparison of model built peptides representing the common secondary structural elements. Dynamical aspects on this new surface are examined using a molecular dynamics trajectory of Basic Pancreatic Trypsin Inhibitor.     

Components of the blood acid-base disturbance that accompanies urethane anaesthesia in rats during normothermia and hypothermia

1. We have studied the components of the metabolic acidosis that accompanies urethane anaesthesia in rats, both with and without the hypothermia that results from this anaesthesia. 2. Acid-base disturbances were analysed with an approach based on Stewart's analysis of acid-base chemistry. 3. The pH fall in the blood of normothermic anaesthetized rats (body temperature Tb) = 37 degrees C) was related to increases in plasma anions (lactate and [Cl-]), which decreased the strong ion difference ([SID]), as well as to increase the weak acid buffers due to increases in albumin. 4. A stronger metabolic acidosis was found in the blood of rats with hypothermia induced by urethane (Tb = 32 degrees C). Although plasma lactate was unchanged in hypothermic rats, [SID] decreased due to alterations in the plasma ionic balance. The metabolic acidosis found in hypothermia was also associated with increased weak acid buffers due to increases in albumin and inorganic phosphate. Further to hyperphosphataemia, signs of acute renal disfunction, such as increases in plasma [Mg2+] and blood urea nitrogen were found. Plasma retention of endogenous acids together with the retention of acid end-products of the metabolism of urethane because of acute renal failure may have contributed to strengthening the fall in pH and [HCO3-] found in urethane-induced hypothermic rats.     

Gallbladder motility and cholecystokinin release during long-term enteral nutrition in patients with Crohn's disease

BACKGROUND: Gallbladder bile stasis during long-term continuous enteral feeding may contribute to the high prevalence of gallstones in patients with Crohn's disease. We therefore examined the effects of continuous enteral nutrition on gallbladder motility and cholecystokinin (CCK) release in six patients. METHODS: Gallbladder volume was measured ultrasonographically for 12 h on days 1 (start), 8, 22 (6-h interruption of enteral feeding), 36, and 43 (end) of enteral feeding. Plasma CCK was assessed at several time points. RESULTS: Initial fasting gallbladder volume was 19.3 +/- 4.5 (mean +/- SEM) ml, which decreased to 4.9 +/- 3.6 ml after start of feeding. CCK increased from 1.5 +/- 0.3 to 3.9 +/- 1.1 pmol/l. On days 8 and 36 the gallbladder was almost completely contracted, and CCK increased to 7.5 +/- 2.7 and 8.3 +/- 2.6 pmol/l, respectively. On days 22 and 43 gallbladder volume increased, and CCK decreased rapidly to fasting concentrations after interruption of feeding. CONCLUSIONS: During continuous enteral nutrition the gallbladder is completely contracted, and CCK concentrations remain elevated. It is therefore unlikely that long-term enteral nutrition contributes to the increased prevalence of gallstones in patients with Crohn's disease.