Metyrapone
Cortodoxone
17-Hydroxycorticosteroids
Steroid 11-beta-Hydroxylase
Hydrocortisone
Corticosterone
Adrenocorticotropic Hormone
Imipramine
Antimetabolites
Cytochrome P-450 Enzyme System
Cushing Syndrome
Monocyte activation in rheumatoid arthritis (RA): increased integrin, Fc gamma and complement receptor expression and the effect of glucocorticoids. (1/262)
The aim of this work was to study the expression of beta 1- and beta 2-integrins, CR1, CD44 and Fc gamma receptors on peripheral blood monocytes in RA. The expression of these receptors was measured by flow cytometry, before and after treatment with low-dose prednisolone. Expression of the same receptors was also measured before and after treatment with metyrapone, a substance that inhibits the synthesis of cortisol in the adrenals. The expression of the beta 2-integrins CD11a, CD11b and CD18, of CD35 (CR1), and of Fc gamma RII and Fc gamma RI (CD32 and CD64) on monocytes was elevated in the RA patients compared with healthy controls, while the expression of the beta 1-integrins (CD29, CD49d, CD49f) was unaffected. A significant correlation between monocyte expression of CD64 and C-reactive protein (CRP), and blood platelet count, respectively, was found in the group of patients with RA. After 4-6 weeks of treatment with low-dose prednisolone, the expression on the monocytes of CD11a, CD11b, CD18, CD35, CD32 and CD64 was normalized. A significant correlation (r = 0.64, P = 0.02) was found between the decrease in expression of CD11b and clinical improvement after prednisolone treatment. Two days of metyrapone treatment, which significantly lowered the serum cortisol levels, elevated the expression of CD35 and CD49f. Priming of peripheral monocytes seems to be one of the mechanisms behind the recruitment of monocytes to the rheumatoid synovium. One reason for the good clinical effects of prednisolone in RA could be a down-regulation of adhesion and phagocytosis receptors on monocytes. (+info)Roles of aldosterone and angiotensin in maturation of sodium appetite in furosemide-treated rats. (2/262)
When rats are treated with furosemide, there is a rapid natriuresis. However, increased sodium appetite does not occur until some time later. One hypothesis to explain this delay is that increased circulating levels of the hormones of sodium depletion prime or sensitize the brain circuits involved in sodium appetite, perhaps by induction of target gene(s). In the present study, we describe the time course of the temporal maturation of sodium appetite after furosemide treatment and the associated changes in plasma levels of ANG II and aldosterone and in plasma volume. Sodium appetite is modest 3 h after furosemide treatment, is increased after 12 h, and is still larger after 24 h. This pattern is evident with repeated testing. Plasma levels of aldosterone and plasma renin activity are substantially increased 3 h after furosemide treatment, and so the NaCl appetite cannot result simply from progressively increasing levels of these hormones. Furthermore, activation of the subfornical organ and the ventral lamina terminalis, assessed with c-Fos immunocytochemistry, did not differ across these three times. Metyrapone, an inhibitor of adrenal steroid synthesis, was used to examine sodium appetite in the absence of elevations in aldosterone after furosemide treatment. Although metyrapone effectively blocked the increase in aldosterone, it was without effect on the appetite 3 or 24 h after furosemide treatment. Furthermore, elevations of plasma aldosterone by the use of minipumps for several days before furosemide treatment did not prime or potentiate but instead tended to inhibit the induced sodium appetite, despite achieving levels of aldosterone and plasma renin activity typically associated with a robust sodium appetite. Infusions of DOCA gave a similar result. Lastly, minipump infusions of ANG II also did not potentiate sodium appetite. Thus neither addition nor subtraction of these hormones alone influenced sodium appetite under these conditions. (+info)Radioimmunoassay for 11-deoxycortisol using iodine-labeled tracer. (3/262)
A simple and sensitive radioimmunoassay for 11-deoxycortisol was developed. The antiserum produced in rabbits by immunizing with a complex of 11-deoxycortisol-3-oxime and bovine serum albumin (BSA) has little cross-reactivity with other endogenous steroids. The immunoassay procedure requires only one-step ethanol denaturation of binding proteins in plasma and extraction by an organic solvent can be omitted. Furthermore, use of 125I-labeled tracer significantly simplify the counting procedure. The method is sensitive enough to detect 1 microng/100 ml of 11-deoxycortisol. Plasma 11-deoxycortisol levels measured by this method after the administration of a single dose of metyrapone ranged from 5.0 to 19.2 microng/100 ml, whereas they were 0 to 4.0 microng/100 ml in hypopituitary patients. It is concluded that this simple method is useful for the routine assay of plasma 11-deoxycortisol as a parameter of the metyrapone tests. (+info)Thymus-derived glucocorticoids set the thresholds for thymocyte selection by inhibiting TCR-mediated thymocyte activation. (4/262)
Selection processes in the thymus eliminate nonfunctional or harmful T cells and allow the survival of those cells with the potential to recognize Ag in association with self-MHC-encoded molecules (Ag/MHC). We have previously demonstrated that thymus-derived glucocorticoids antagonize TCR-mediated deletion, suggesting a role for endogenous thymic glucocorticoids in promoting survival of thymocytes following TCR engagement. Consistent with this hypothesis, we now show that inhibition of thymus glucocorticoid biosynthesis causes an increase in thymocyte apoptosis and a decrease in recovery that are directly proportional to the number of MHC-encoded molecules present and, therefore, the number of ligands available for TCR recognition. Expression of CD5 on CD4+CD8+ thymocytes, an indicator of TCR-mediated activation, increased in a TCR- and MHC-dependent manner when corticosteroid production or responsiveness was decreased. These results indicate that thymus-derived glucocorticoids determine where the window of thymocyte selection occurs in the TCR avidity spectrum by dampening the biological consequences of TCR occupancy and reveal that glucocorticoids mask the high percentage of self-Ag/MHC-reactive thymocytes that exist in the preselection repertoire. (+info)Role of endogenous cortisol in basal liquid clearance from distal air spaces in adult guinea-pigs. (5/262)
1. We investigated the role of endogenous cortisol in the modulation of distal air space liquid clearance in adult guinea-pigs. Cortisol synthesis was inhibited with the 11-beta-hydroxylase inhibitor metyrapone (0-7 days pretreatment). After cortisol synthesis inhibition, distal air space liquid clearance was measured by the increase in concentration of an instilled 5 % albumin solution after 1 h. 2. Two days of metyrapone pretreatment resulted in a 46+/-19 % decrease in plasma cortisol levels compared with control, which was paralleled by a 60+/-13 % decrease in distal air space liquid clearance. The Na+ channel inhibitor amiloride inhibited 40+/-22 % of distal air space liquid clearance in control animals but did not inhibit distal air space liquid clearance in the metyrapone-pretreated group. Co-injection of dexamethasone prevented the inhibition by metyrapone and the amiloride sensitivity of distal air space liquid clearance was greater than in control animals. After 7 days of metyrapone pretreatment, plasma cortisol levels and distal air space liquid clearance were not significantly different from normal, but amiloride sensitivity was greater than in control animals (91+/-37%). 3. Pretreatment with emetine, a protein synthesis inhibitor, reduced distal air space liquid clearance in control animals and in dexamethasone-co-injected animals, but failed to inhibit distal air space liquid clearance after metyrapone pretreatment. Expression of the epithelial sodium channel alpha-subunit (alphaENaC) mRNA in lung tissue was decreased after 2 days of metyrapone pretreatment and after 7 days pretreatment or after co-injection with dexamethasone, alphaENaC mRNA expression was restored towards control levels. 4. Thus, endogenous cortisol is important for maintaining normal liquid balance in the adult guinea-pig lung and a critical regulatory pathway is by modulation of ENaC expression and/or function. (+info)Postischemic steroid modulation: effects on hippocampal neuronal integrity and synaptic plasticity. (6/262)
Elimination of corticosteroids after ischemia, by removal of the adrenals, has been reported to preserve neuronal integrity later. To establish the therapeutic potential of this observation, the authors address two questions: first, whether clinically more relevant steroid manipulations after ischemia exert similar protective effects, and second, whether changes in synaptic functioning occur along with structural alterations. To test this, the authors treated animals immediately after hypoxia-ischemia with (1) the steroid synthesis inhibitor metyrapone, (2) the synthetic glucocorticoid receptor agonist dexamethasone, (3) the selective glucocorticoid antagonist RU 38486, or (4) corticosterone. Metyrapone, but none of the other compounds, attenuated the occurrence of seizures immediately after ischemia. Twenty-four hours after hypoxia-ischemia, CAI hippocampal field potentials in response to stimulation of Schaffer/commissural fibers were found to be reduced. The attenuation of synaptic transmission was partly prevented by metyrapone. None of the other experimental treatments influenced the impaired synaptic function. Gross morphologic analysis revealed no differences in the loss of neuronal structure between the experimental groups at this time point. Taken together, these data suggest that metyrapone preserves neuronal functioning despite loss of neuronal structure. The authors tentatively conclude that preventing the ongoing production of steroids shortly after ischemia can delay and attenuate the appearance of ischemia-related pathology. (+info)Characterization of the binding of [3H]-clobenpropit to histamine H3-receptors in guinea-pig cerebral cortex membranes. (7/262)
1 We have investigated the binding of a novel histamine H3-receptor antagonist radioligand, [3H]- clobenpropit ([3H]-VUF9153), to guinea-pig cerebral cortex membranes. 2 Saturation isotherms for [3H]-clobenpropit appeared biphasic. Scatchard plots were curvilinear and Hill plot slopes were significantly less than unity (0.63+/-0.03; n = 12+/-s.e.mean). The radioligand appeared to label two sites in guinea-pig cerebral cortex membranes with apparent affinities (pKD') of 10.91+/-0.12 (Bmax = 5.34+/-0.85 fmol mg(-1) original wet weight) and 9.17+/-0.16 (Bmax = 23.20+/-6.70 fmol mg(-1)). 3 In the presence of metyrapone (3 mM) or sodium chloride (100 mM), [3H]-clobenpropit appeared to label a homogeneous receptor population (Bmax=3.41+/-0.46 fmol mg-1 and 3.49+/-0.44 fmol mg(-1), pKD' = 10.59+/-0.17 and 10.77+/-0.02, respectively). Scatchard plots were linear and Hill slopes were not significantly different from unity (0.91+/-0.04 and 0.99+/-0.02, respectively). Granisetron (1 microM), rilmenidine (3 microM), idazoxan (0.3 microM), pentazocine (3 microM) and 1,3-di-(2-tolyl)guanidine (0.3 microM) had no effect on the binding of [3H]-clobenpropit. 4 The specific binding of [3H]-clobenpropit appeared to reach equilibrium after 25 min at 21+/-3 degrees C and remained constant for >180 min. The estimated pKD' (10.27+/-0.27; n = 3+/-s.e.mean) was not significantly different from that estimated by saturation analysis in the presence of metyrapone. 5 A series of histamine H3-receptor ligands expressed affinity values for sites labelled with [3H]-clobenpropit which were not significantly different from those estimated when [3H]-R-alpha-MH was used to label histamine H3-receptors in guinea-pig cerebral cortex membranes. (+info)Degradation of an alkaloid pheromone from the pale-brown chafer, Phyllopertha diversa (Coleoptera: Scarabaeidae), by an insect olfactory cytochrome P450. (8/262)
The pale-brown chafer, Phyllopertha diversa, utilizes an unusual alkaloid, 1,3-dimethyl-2,4-(1H,3H)-quinazolinedione, as its sex pheromone. This compound is rapidly degraded in vitro by the antennal protein extracts from this scarab beetle. Demethylation at the N-1 position and hydroxylation of the aromatic ring have been identified as the major catabolic pathways. The enzyme responsible for the pheromone degradation is membrane-bound, requires NAD(P)H for activity and is sensitive to cytochrome P450 inhibitors, such as proadifen and metyrapone. The ability to metabolize this unusual pheromone was not detected in 12 species tested, indicating that the P450 system, specific to male P. diversa antennae, has evolved as a mechanism for olfactory signal inactivation. (+info)Metyrapone is a medication that is primarily used in the diagnosis and treatment of Cushing's syndrome, a condition characterized by excessive levels of cortisol hormone in the body. It works as an inhibitor of steroidogenesis, specifically blocking the enzyme 11-beta-hydroxylase, which is involved in the production of cortisol in the adrenal gland.
By inhibiting this enzyme, metyrapone prevents the formation of cortisol and leads to an accumulation of its precursor, 11-deoxycortisol. This can help restore the balance of hormones in the body and alleviate symptoms associated with Cushing's syndrome.
It is important to note that metyrapone should only be used under the supervision of a healthcare professional, as it can have significant side effects and interactions with other medications.
I am not aware of a medical definition for "Cortodoxone." It is possible that this term is not recognized in the field of medicine as it does not appear to be a commonly used medication, treatment, or diagnostic tool. If you have any more information about where you encountered this term or its potential meaning, I would be happy to try and provide further clarification.
17-Hydroxycorticosteroids are a class of steroid hormones that are produced in the adrenal gland. They are formed from the metabolism of cortisol, which is a hormone that helps regulate metabolism, immune response, and stress response. 17-Hydroxycorticosteroids include compounds such as cortisone and corticosterone.
These hormones have various functions in the body, including:
* Regulation of carbohydrate, fat, and protein metabolism
* Suppression of the immune system
* Modulation of the stress response
* Influence on blood pressure and electrolyte balance
Abnormal levels of 17-hydroxycorticosteroids can indicate problems with the adrenal gland or pituitary gland, which regulates adrenal function. They are often measured in urine or blood tests to help diagnose conditions such as Cushing's syndrome (overproduction of cortisol) and Addison's disease (underproduction of cortisol).
Proadifen is not typically referred to as a medical term or definition in modern medicine. However, it is an old antihistamine drug that was used in the past for its properties as a monoamine oxidase inhibitor (MAOI). MAOIs were used primarily in the treatment of depression but have largely been replaced by newer classes of drugs due to their potential for serious side effects.
Here is a brief medical definition of Proadifen as an MAOI:
Proadifen (SKF-525A): An older, nonselective and irreversible monoamine oxidase inhibitor (MAOI) that was used in the past for its antidepressant effects. Its use has been largely discontinued due to the risk of serious adverse reactions, such as hypertensive crises, when combined with certain foods or medications containing tyramine.
Steroid 11-beta-hydroxylase is a crucial enzyme involved in the steroidogenesis pathway, specifically in the synthesis of cortisol and aldosterone, which are vital hormones produced by the adrenal glands. This enzyme is encoded by the CYP11B1 gene in humans.
The enzyme's primary function is to catalyze the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to aldosterone through the process of hydroxylation at the 11-beta position of the steroid molecule. Cortisol is a critical glucocorticoid hormone that helps regulate metabolism, immune response, and stress response, while aldosterone is a mineralocorticoid hormone responsible for maintaining electrolyte and fluid balance in the body.
Deficiencies or mutations in the CYP11B1 gene can lead to various disorders, such as congenital adrenal hyperplasia (CAH), which may result in impaired cortisol and aldosterone production, causing hormonal imbalances and associated symptoms.
Oxazepam is a benzodiazepine medication that is primarily used to treat anxiety disorders and symptoms such as sleeplessness and irritability. It works by enhancing the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits the activity of certain neurons in the brain, producing a calming effect.
In medical terms, oxazepam can be defined as follows:
Oxazepam is a Schedule IV controlled substance, indicating that it has a potential for abuse and dependence. It is available in tablet form and is typically taken two to four times per day. Common side effects of oxazepam include drowsiness, dizziness, and weakness. More serious side effects can include memory problems, confusion, and difficulty breathing.
It's important to note that oxazepam should only be used under the supervision of a healthcare provider, as it can have significant risks and interactions with other medications. It is not recommended for use in pregnant women or those with a history of substance abuse.
Hydrocortisone is a synthetic glucocorticoid, which is a class of steroid hormones. It is identical to the naturally occurring cortisol, a hormone produced by the adrenal gland that helps regulate metabolism and helps your body respond to stress. Hydrocortisone has anti-inflammatory effects and is used to treat various inflammatory conditions such as allergies, skin disorders, and autoimmune diseases. It works by suppressing the immune system's response to reduce swelling, redness, itching, and other symptoms caused by inflammation.
Hydrocortisone is available in different forms, including oral tablets, topical creams, lotions, gels, and ointments, as well as injectable solutions. The specific use and dosage depend on the condition being treated and the individual patient's medical history and current health status.
As with any medication, hydrocortisone can have side effects, especially when used in high doses or for extended periods. Common side effects include increased appetite, weight gain, mood changes, insomnia, and skin thinning. Long-term use of hydrocortisone may also increase the risk of developing osteoporosis, diabetes, cataracts, and other health problems. Therefore, it is essential to follow your healthcare provider's instructions carefully when using this medication.
Corticosterone is a hormone produced by the adrenal gland in many animals, including humans. It is a type of glucocorticoid steroid hormone that plays an important role in the body's response to stress, immune function, metabolism, and regulation of inflammation. Corticosterone helps to regulate the balance of sodium and potassium in the body and also plays a role in the development and functioning of the nervous system. It is the primary glucocorticoid hormone in rodents, while cortisol is the primary glucocorticoid hormone in humans and other primates.
Adrenocorticotropic Hormone (ACTH) is a hormone produced and released by the anterior pituitary gland, a small endocrine gland located at the base of the brain. ACTH plays a crucial role in the regulation of the body's stress response and has significant effects on various physiological processes.
The primary function of ACTH is to stimulate the adrenal glands, which are triangular-shaped glands situated on top of the kidneys. The adrenal glands consist of two parts: the outer cortex and the inner medulla. ACTH specifically targets the adrenal cortex, where it binds to specific receptors and initiates a series of biochemical reactions leading to the production and release of steroid hormones, primarily cortisol (a glucocorticoid) and aldosterone (a mineralocorticoid).
Cortisol is involved in various metabolic processes, such as regulating blood sugar levels, modulating the immune response, and helping the body respond to stress. Aldosterone plays a vital role in maintaining electrolyte and fluid balance by promoting sodium reabsorption and potassium excretion in the kidneys.
ACTH release is controlled by the hypothalamus, another part of the brain, which produces corticotropin-releasing hormone (CRH). CRH stimulates the anterior pituitary gland to secrete ACTH, which in turn triggers cortisol production in the adrenal glands. This complex feedback system helps maintain homeostasis and ensures that appropriate amounts of cortisol are released in response to various physiological and psychological stressors.
Disorders related to ACTH can lead to hormonal imbalances, resulting in conditions such as Cushing's syndrome (excessive cortisol production) or Addison's disease (insufficient cortisol production). Proper diagnosis and management of these disorders typically involve assessing the function of the hypothalamic-pituitary-adrenal axis and addressing any underlying issues affecting ACTH secretion.
Imipramine is a tricyclic antidepressant (TCA) medication that is primarily used to treat depression. It works by increasing the levels of certain neurotransmitters, such as serotonin and norepinephrine, in the brain. Imipramine has been found to be effective in treating various types of depression, including major depressive disorder, dysthymia, and depression that is resistant to other treatments.
In addition to its antidepressant effects, imipramine is also used off-label for the treatment of several other conditions, such as anxiety disorders, attention deficit hyperactivity disorder (ADHD), enuresis (bedwetting), and chronic pain.
Imipramine was first synthesized in the 1950s and has been widely used since then. It is available in various forms, including immediate-release tablets, extended-release capsules, and liquid solutions. As with all medications, imipramine can have side effects, which may include dry mouth, blurred vision, constipation, dizziness, and sedation. In rare cases, it can cause more serious side effects, such as cardiac arrhythmias or seizures.
It is important to use imipramine under the close supervision of a healthcare provider, as dosages may need to be adjusted based on individual patient needs and responses to treatment. Additionally, imipramine should not be stopped abruptly, as doing so can lead to withdrawal symptoms or a recurrence of depression.
Antimetabolites are a class of drugs that interfere with the normal metabolic processes of cells, particularly those involved in DNA replication and cell division. They are commonly used as chemotherapeutic agents to treat various types of cancer because many cancer cells divide more rapidly than normal cells. Antimetabolites work by mimicking natural substances needed for cell growth and division, such as nucleotides or amino acids, and getting incorporated into the growing cells' DNA or protein structures, which ultimately leads to the termination of cell division and death of the cancer cells. Examples of antimetabolites include methotrexate, 5-fluorouracil, and capecitabine.
The Cytochrome P-450 (CYP450) enzyme system is a group of enzymes found primarily in the liver, but also in other organs such as the intestines, lungs, and skin. These enzymes play a crucial role in the metabolism and biotransformation of various substances, including drugs, environmental toxins, and endogenous compounds like hormones and fatty acids.
The name "Cytochrome P-450" refers to the unique property of these enzymes to bind to carbon monoxide (CO) and form a complex that absorbs light at a wavelength of 450 nm, which can be detected spectrophotometrically.
The CYP450 enzyme system is involved in Phase I metabolism of xenobiotics, where it catalyzes oxidation reactions such as hydroxylation, dealkylation, and epoxidation. These reactions introduce functional groups into the substrate molecule, which can then undergo further modifications by other enzymes during Phase II metabolism.
There are several families and subfamilies of CYP450 enzymes, each with distinct substrate specificities and functions. Some of the most important CYP450 enzymes include:
1. CYP3A4: This is the most abundant CYP450 enzyme in the human liver and is involved in the metabolism of approximately 50% of all drugs. It also metabolizes various endogenous compounds like steroids, bile acids, and vitamin D.
2. CYP2D6: This enzyme is responsible for the metabolism of many psychotropic drugs, including antidepressants, antipsychotics, and beta-blockers. It also metabolizes some endogenous compounds like dopamine and serotonin.
3. CYP2C9: This enzyme plays a significant role in the metabolism of warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. CYP2C19: This enzyme is involved in the metabolism of proton pump inhibitors, antidepressants, and clopidogrel.
5. CYP2E1: This enzyme metabolizes various xenobiotics like alcohol, acetaminophen, and carbon tetrachloride, as well as some endogenous compounds like fatty acids and prostaglandins.
Genetic polymorphisms in CYP450 enzymes can significantly affect drug metabolism and response, leading to interindividual variability in drug efficacy and toxicity. Understanding the role of CYP450 enzymes in drug metabolism is crucial for optimizing pharmacotherapy and minimizing adverse effects.
Cushing syndrome is a hormonal disorder that occurs when your body is exposed to high levels of the hormone cortisol for a long time. This can happen due to various reasons such as taking high doses of corticosteroid medications or tumors that produce cortisol or adrenocorticotropic hormone (ACTH).
The symptoms of Cushing syndrome may include:
* Obesity, particularly around the trunk and upper body
* Thinning of the skin, easy bruising, and purple or red stretch marks on the abdomen, thighs, breasts, and arms
* Weakened bones, leading to fractures
* High blood pressure
* High blood sugar
* Mental changes such as depression, anxiety, and irritability
* Increased fatigue and weakness
* Menstrual irregularities in women
* Decreased fertility in men
Cushing syndrome can be diagnosed through various tests, including urine and blood tests to measure cortisol levels, saliva tests, and imaging tests to locate any tumors. Treatment depends on the cause of the condition but may include surgery, radiation therapy, chemotherapy, or adjusting medication dosages.