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A model of Arthus pleurisy: modulation by various pharmacologic and therapeutic agents.

A reversed passive Arthus reaction was elicited in the rat pleural cavity. The kinetics of this inflammatory response indicate that exudate volume (cells and fluid) reaches a maximum level approximately 2 to 4 hr postantibody challenge. The neutrophil is the major cellular constituent of the pleural exudate during the first 12 hr of this reaction, reaching peak values at 4 hr; whereas, the monocyte predominates between 15 and 24 hr. Lymphocytes, eosinophils, and mast cells were also identified in the pleural exudates. The serotonin antagonists, cyproheptadine and methylsergide, and the antihistamine, chlorpheniramine, demonstrated marginal activity in the Arthus pleurisy model. The histamine antagonist, metiamide, was inactive. The nonsteroidal anti-inflammatory agents, flurbiprofen, ibuprofen, indomethacin, and benoxaprofen caused a modest suppression of exudate volume (18-32%) and cell accumulation (28-34%). The fluid and cellular components of the Arthus reaction were significantly inhibited by dexamethasone, triamcinolone, paramethasone, and prednisolone. The oral gold preparation, auranofin, had a pronounced effect on exudate volume; whereas, other antirheumatic agents such as D-penicillamine, azathioprine, and chloroquine had no effect on the Arthus pleurisy reaction. The immunomodulator, levamisole, suppressed exudate volume, but had no effect on cell accumulation in the pleural cavity.

Adrenal Cortex Hormones↗

Evaluation of the effects of various anti-arthritic drugs on type II collagen-induced mouse arthritis model.

A battery of drugs which are commonly used as therapeutic agents for arthritis was tested for effects on the inflammatory and immunological responses of DBA/1J mice, after immunization with type II collagen. All the drugs were tested at more than one dosage. The mice were protected from the development of arthritis by treatment with paramethasone (0.25 mg/kg/day) or cyclophosphamide (5 mg/kg/day). The nonsteroidal anti-inflammatory drugs used in these studies, viz. aspirin (200 mg/kg/day), benoxaprofen (100 mg/kg/day) and naproxen (200 mg/kg/day), had no significant effect on the joint involvement, although naproxen and benoxaprofen at these high doses caused some reduction of immune responses of mice to collagen. Chloroquine (100 mg/kg/day), levamisol (50 mg/kg/day) and gold chlorophosphene (5 mg/kg/day) had no effect on the inflammatory or humoral response, while treatment with D-penicillamine (100 mg/kg/day) led to an early onset of arthritis in mice. These data suggest that the type II collagen-induced mouse arthritis model may not be highly suitable for detection of the traditional nonsteroidal anti-inflammatory class of drugs or the anti-rheumatic drugs, although the possibility remains that some new and novel immunosuppressive agents may be detected with this model.

Adjuvants, Immunologic↗

Tachon's syndrome (suracute back and/or thoracic pain following local injections of corticosteroids). A report of 318 French cases.

OBJECTIVES: To assess the frequency, features, and outcome of excruciating lumbar, dorsal, and/or thoracic pain following injections of local corticosteroids in rare instances. METHODS: A questionnaire mailed to 500 French rheumatologists. RESULTS: Three hundred and eighteen cases were reported by 92 rheumatologists (one event per 8000 injections or 6.5 years of practice), following injections into lumbar epidural space (39%), an upper limb (30%), a lower limb (mostly the heel) (24%), or other locations (7%), of cortivazol (67%), hydrocortisone (25%), betamethasone (7%), or paramethasone (1%). Symptoms occurred 1-5 min (78%) or less than 1 min (22%) after injection, and highly acute axial pain usually lasted for less than 5 min (34%) or 5-15 min (51%). In addition to pain in lumbar (84%) and/or dorsal regions (25%) [often preceded or associated with thoracic pain (36%)], other signs were: anxiety (87%), shortness of breath (64%), facial flushing (64%), diffuse sweating (41%), agitation (29%), transient cough (23%), abdominal pain (20%), transient hypertension (15%), paleness (10%), hypotension (8%), diarrhoea (3%) and headache (3%). None of these patients was known to be allergic, and urticaria developed in only 2%. Outcome was favourable in all cases (even though 4/318 patients were transiently hospitalised) with an overall duration of 25 +/- 71 min. Another injection was performed later in 146/318 cases (46%), but Tachon's syndrome recurred in only 20 of these 146 patients (14%). CONCLUSION: The outcome of this impressive syndrome seems excellent. Tachon's syndrome might be the venous counterpart of Nicolau's syndrome (injection of corticosteroids in an artery).

Adrenal Cortex Hormones↗

Assessment of topical anti-inflammatory activity in rats with cantharidin-induced inflammation.

Topical application of 400 mug of cantharidin to the rat's ear caused an approximate doubling in the mean weight of uniform ear punch samples when compared to vehicle-treated controls at 72 hr, and produced a maximal response at 7 days. Dexamethasone reduced the increase in weight when applied topically, but was ineffective when given subcutaneously or orally at the same doses. Hydrocortisone, prednisolone, triamcinolone, betamethasone, flurometholone, paramethasone acetate, fluocinolone acetonide, fluocinonide, and flurandrenolide showed significant suppression of cantharidin-induced inflammation. Cholesterol, diphenhydramine, tripelennamine, chlorpheniramine, promethazine, cyproheptadine, epinephrine, phenylephrine, alpha-tocopherol, indomethacin, and bufexamac were inactive. It is suggested that the procedure employed may be useful in the screening and evaluation of topical anti-inflammatory agents.

Administration, Topical↗

[The high pressure liquid chromatography of corticoids. II. Analysis of synthetic corticoids in blood and urine (author's transl)].

The high pressure liquid chromatographic (HPLC) technique was developed to separate and quantitate the synthetic corticosteroids (s-CS) which are widely used clinically. 1) 12 kinds of s-CS in alcoholic solvent and 2) some of their metabolites in the plasma and urine of healthy subjects with oral administration of s-CS were investigated for the preliminary work. The results are summarized as follows: 1) Cortisol sodium phosphate, Dexamethasone 21, disodium phosphate, Paramethasone acetate, Cortisol acetate, Cortisone acetate, Methylprednisolone acetate, Prednisone, Dexamethasone, 9 alpha-fluorocortisol, Betamethasone, Triamcinolone, and Prednisolone in ethanol were clearly separated by HPLC from Cortisol (F). In the suitable condition of the HPLC (LC-2 type) with a Zorbax SIL column, organic solvent (cyclohexane:dichloromethane:ethanol = 9:4:1)-carrier mobile phases and UV detector, the retention time of each s-CS was obviously different from that of F. The calibration curve was obtained in a linear line with regards to each s-CS. The mean recovery was 97.6% and the coefficient of variation were 1.6 (intraassay) and 7.2 (interassay)%. The sensitivity of the steroid determination was 200pg order. 2) The serial changes in plasma concentrations of s-CS; CS-metabolites and endogenous F were shown in 3 healthy males and 2 females following oral administration of the s-CS. The separated metabolites in number and quality depended on the kind of s-CS. Prednisone and other kinds of the acidified products were separated from prednisolone in the plasma and urinary samples of the healthy subjects as well as Addisonian patients. In conclusion, the HPLC method is useful for the separation and quantitation of the UV-absorbing CS of human plasma and urine. The obtained chromatograms may be an indication of the metabolic state of the subject with treatment of s-CS.

Adrenal Cortex Hormones↗

Potent inhibition of interleukin 1 beta-mediated human melanoma (A375.6) lysis by corticosteroids, staurosporine, and tilorone.

The mechanism of human interleukin (IL)-1 beta-mediated cytolysis was studied in a human melanoma cell line, A375.6. Purified recombinant human IL-1 beta produced 50% cytocidal activity at 50 pg/ml. A variety of compounds were tested for their ability to interfere with A375.6 lysis. Compounds were added simultaneously with IL-1 beta (100 pg/ml), and tumor cytolysis was measured after 72 hr of culture by release of 125I from DNA of A375.6 cells labeled with [125I]-dUrd. A variety of anti-inflammatory/immunosuppressive agents (including auranofin, chloroquine, cyclosporin A, d-penicillamine) and several cyclooxygenase/lipoxygenase inhibitors (AA-861, BW755c, and indomethacin) lacked protective activity. Similarly, phospholipase inhibitors (mepacrine and 4-bromophenacyl bromide), putrescine, inhibitors of lysosomal activity (chloroquine and NH4Cl), calcium channel blockers (nifedipine and verapamil), calmodulin inhibitors (W-7 and calmidazolium), and inhibitors of ADP ribosylation (nicotinamide and 3-aminobenzamide) were inactive. In contrast, corticosteroids (dexamethasone, hydrocortisone, and paramethasone acetate), tilorone, and protein kinase C inhibitors (1-[5-isoquinolinyl-sulfonyl]-2-methylpiperazine and staurosporine) significantly inhibited IL-1 beta-mediated A375.6 cytolysis. These compounds also interfered with tumor necrosis factor-mediated lysis of A375.6, suggesting common mechanisms of tumor cytotoxicity by these monokines. This model may be useful for delineating intracellular biochemical events integral to IL-1 action.

Adrenal Cortex Hormones↗

Lung enzymes in emphysematous rats: effects of progestagens, antiphlogistics and metabolic inhibitors.

Chronic exposure of rats to 10% aerosols of papain or trypsin resulted in marked increases in lung weights and lung beta-glucuronidase and arylsulfatase activities. Destruction of alveolar walls was demonstrated microscopically as a decrease in the number of air spaces touching a line of known length. The pregnenes, progesterone and medroxyprogesterone acetate, but not the 19-nortestosterone derivative norethindrone, partially prevented the papain-induced breakdown of alveolar septa and elevation of beta-glucuronidase. The steroidal anti-inflammatory agent, paramethasone, completely inhibited the rise in lung weight and beta-glucuronidase activity, but did not prevent destruction of alveolar walls. The non-steroidal anti-inflammatory agent, indomethacin, afforded little or no protection. Limited prophylaxis against both histological and enzymatic changes was observed in rats treated with the anti-metabolite, cyclophosphamide, and the proteolytic enzyme inhibitor, aprotinin. The various lung abnormalities resulting from papain inhalation may thus be individually influenced by specific pharmacologic agents.

Animals↗

[Herpes zoster of the right cervical region associated with right facial nerve palsy and hoarseness].

A 69-year-old man was suffering from herpes zoster on his 2nd and 3rd right cervical spinal segments and 3rd branch of the trigeminal nerve. He came to our hospital on his 10th illness day and was treated with continuous cervical epidural block, intravenous infusion of acyclovir for five days, and oral paramethasone and Vitamin B12. Oh his 18th illness day, right facial nerve palsy and hoarseness became clear. His cerebrospinal fluid showed no abnormality except cell count 23 x 3 mm-2. No clear paralysis of vocal cords was detected on laryngoscopy. He was also treated with right stellate ganglion block starting on his 21st illness day. His pain and facial nerve palsy recovered completely by his 68th illness day, but hoarseness continued about two months. The hoarseness might be a result of spread of the disease 1) by cerebrospinal fluid, 2) by contact with the 3rd cervical nerve and vagal nerve via accessory nerve, and 3) direct effect on the vocal cords and the muscles controlling them. Herpes zoster on the head and neck region shows various complications and we should follow its course cautiously.

Aged↗

Effects of various anti-inflammatory drugs on type II collagen-induced arthritis in rats.

The effects of some commonly used anti-inflammatory and anti-arthritic drugs on the inflammatory and immunological manifestations of type II collagen-induced arthritis in rats were studied. Among the anti-inflammatory drugs tested at a given dosage (mg/kg/day), benoxaprofen (10), aspirin (25) and indomethacin (3) inhibited the hind paw swelling and anti-type II collagen antibody formation in type II collagen-treated rats. Benoxaprofen also inhibited the delayed type hypersensitivity (DTH) response to type II collagen. Phenylbutazone (30) and fenoprofen (40) partially suppressed the paw swelling, but had no significant effect on humoral and cellular responses. Among the other anti-arthritic drugs, levamisol (25), chloroquine (25) and D-penicillamine significantly suppressed the paw swelling, anti-type II collagen antibody titres and DTH response. Gold chlorophosphene (10) and colchicine (3) had no effect on any of these three parameters. Paramethasone (0.1), cyclophosphamide (1) and azathioprine (10) were very effective when dosed daily, or once (at a different dose) 72 hr prior to immunization with type II collagen.

Animals↗

[How to use glucocorticoids in ophthalmology].

Administration of glucocorticoid, one of the corticosteroid hormones, is one of the most important therapeutic strategy in ophthalmological treatment. Almost all kinds of glucocorticoid agents are commercially available for various ocular diseases, including cortisone, hydrocortisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, paramethasone, betamethasone and fluolometholone. Glucocorticoids are administrated in preparations of eye drops, ointments, injections and tablets for local and systemic use. Systemic glucocorticoid treatment should, in general, only be considered when local treatment with eye drops or with injections fail, when the disease is bilateral, or when systemic findings indicate the need. "Producing less severe side effects or complications, obtaining the most efficacy, with long duration" is the main principles in ophthalmological use of glucocorticoids. Steroid cataract (posterior subcapsular opacity) and steroid glaucoma (intraocular pressure elevation) are the two main ocular complications of glucocorticoid administration. Serial slitlamp examination and tonometry are essential to prevent them.

Drug Administration Routes↗

[Toxicoderma caused by prednisone and prednisolone. Value of skin tests in the screening of cross sensitivity].

INTRODUCTION: Allergic reactions to general corticosteroid therapy are uncommon. CASE REPORT: We report a patient with systemic lupus erythematousus who developed skin rash after initiation of prednisone then prednisolone therapy. Histology evidence suggested leukocytoclastic vasculitis. The skin tests (prick tests, intradermoreactions and patch-tests) using a battery of injectable corticosteroids showed a highly positive reaction to prednisolone, methylprednisolone and dexamethasone on the intradermo-reactions 24 hours later. Histology examination of a positive-response showed leukocytoclastic vasculitis associated with eczematiform alterations of the epidermis compatible with a drug reaction. The skin tests however were negative for betamethasone, triamcinolone, paramethasone and hydrocorticose. The patient was treated with betamethasone and no skin reaction was observed. DISCUSSION: Skin tests, particularly intradermo-reactions read 24 hours later would appear to be useful in identifying possible cross-sensitivity.

Aged↗

THE USE OF CHANGES IN CAPILLARY PERMEABILITY IN MICE TO DISTINGUISH BETWEEN NARCOTIC AND NONNARCOTIC ALALGESICS.

An extension of the "squirming test" is described which makes the method specific for nonnarcotic analgesics. The intraperitoneal injection of acetic acid causes squirming and an increase in capillary permeability that is measured by direct estimation of plasma-bound dye (Pontamine Sky Blue) which has leaked into the peritoneal cavity. Nonnarcotic analgesics inhibit squirming and leakage of dye. Values for the oral ED50s for both effects are given for a number of typical compounds. Narcotic analgesics, in doses that produce analgesia, inhibit squirming but do not significantly affect leakage of dye. Drugs that stimulate the central nervous system and also inhibit squirming have no significant effect on leakage of dye over the range of doses which inhibit squirming. Corticosteroids do not significantly inhibit either squirming or leakage of dye.

Acetates↗