The effects of subconjunctival betamethasone on the blood aqueous barrier following cataract surgery: a double-blind randomised prospective study. (57/339)

The aim of this double-blind randomised prospective study was to assess the effect of subconjunctival Betnesol (betamethasone sodium phosphate 0.1%) on the recovery of the blood aqueous barrier (BAB) following cataract surgery in uncomplicated eyes. Twenty patients [10 male, mean age 71.4 (SD 12.7) years] admitted for routine cataract surgery were randomised into two groups. All patients recruited into the study were free of other ocular disease and were not taking any anti-inflammatory medication. Group A received a subconjunctival injection of cefuroxime (125 mg) alone while group B received a subconjunctival injection of both cefuroxime and Betnesol. All surgery was performed by a single surgeon using a standardised surgical technique and all patients received the same postoperative medication. The Kowa laser flare cell meter was used to measure aqueous flare and cells preoperatively and on the first, second, and seventh postoperative day, and at 1 and 3 months following surgery. The code was broken only after all patients had been followed-up for 3 months postoperatively. There was no significant difference between the two groups in aqueous flare and cells at any of the postoperative visits. In this study we were unable to demonstrate any beneficial effect of subconjunctival betamethasone on damage to and recovery of the BAB following cataract surgery in the uncomplicated eye.  (+info)

CHEMOTHERAPY OF ARTHRITIS INDUCED IN RATS BY MYCOBACTERIAL ADJUVANT. (58/339)

Arthritis induced in rats by mycobacterial adjuvant has been used for the study of compounds of known value in the treatment of rheumatoid arthritis in man. The development of the arthritic syndrome in treated and control rats was followed by measuring the changes in foot thickness of both hind-feet with a micrometer. This method allowed the effect of anti-inflammatory compounds to be expressed quantitatively. Anti-inflammatory activity was readily observed in certain steroids, pyrazolidines, salicylates and sodium aurothiomalate. Chloroquine and hydroxychloroquine were inactive. The inhibition obtained by daily treatment with the steroid paramethasone disappeared when treatment was withdrawn.  (+info)

NONSPECIFIC ANTI-INFLAMMATORY AGENTS. SOME NOTES ON THEIR PRACTICAL APPLICATION, ESPECIALLY IN RHEUMATIC DISORDERS. (59/339)

A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented. Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases. Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages. Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis.  (+info)

Motor neuron involvement in a patient with long-term corticosteroid administration. (60/339)

An asthmatic patient with corticosteroid treatment for 45 years presented with slowly progressive limb muscle atrophy. His muscle symptoms were involved in four limbs and tongue, and deep tendon reflexes were exaggerated. Biopsied muscle pathology indicated the presence of neurogenic muscular atrophy in combination with corticosteroid myopathy. Furthermore, 8-hydroxy-deoxyguanosine (8-OH-dG) was prominently increased in mitochondrial and nuclear DNA. An aerobic exercise test demonstrated remarkable serum lactate elevation, which was attenuated by the administration of coenzyme Q10. These findings are consistent with the assumption that long-term corticosteroid administration potentially induces not only myopathy but also motor neuron involvement as in mitochondrial diseases.  (+info)

Can roxithromycin and betamethasone induce acute pancreatitis? A case report. (61/339)

CONTEXT: Acute pancreatitis has been reported in a few cases treated with macrolides or glucocorticoids. CASE REPORT: We report the case of a 58 year old patient who, after 2 days of treatment with roxithromycin and betamethasone, manifested acute pancreatitis. Other causes of the disease were ruled out. No re-occurrence of pancreatitis was observed in a 16 month follow-up. CONCLUSION: Our case sheds new light on glucocorticoid pancreatotoxicity and confirms the role of macrolides as potential pancreatotoxic drugs.  (+info)

Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor alpha promoter in vivo. (62/339)

Tumor necrosis factor alpha (TNF-alpha) contributes to the pathogenesis of both acute and chronic inflammatory diseases and has been a target for the development of new anti-inflammatory drugs. Shikonins, the naphthoquinone pigments present in the root tissues of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), have been reported to exert anti-inflammatory effects both in vitro and in vivo. In this study, we evaluated the effects of shikonin and its derivatives on the transcriptional activation of human TNF-alpha promoter in a gene gun-transfected mouse skin system by using a luciferase reporter gene assay. The crude plant extract of L. erythrorhizon as well as derived individual compounds shikonin, isobutyryl shikonin, acetyl shikonin, dimethylacryl shikonin and isovaleryl shikonin showed significant dose-dependent inhibition of TNF-alpha promoter activation. Among the tested compounds, shikonin and isobutyryl shikonin exhibited the highest inhibition of TNF-alpha promoter activation and also showed significant suppression of transgenic human TNF-alpha mRNA expression and protein production. We demonstrated that shikonin-inhibitory response was retained in the core TNF-alpha promoter region containing the TATA box and a 48-bp downstream sequence relative to the transcription start site. Further our results indicated that shikonin suppressed the basal transcription and activator-regulated transcription of TNF-alpha by inhibiting the binding of transcription factor IID protein complex (TATA box-binding protein) to TATA box. These in vivo results suggest that shikonins inhibit the transcriptional activation of the human TNF-alpha promoter through interference with the basal transcription machinery. Thus, shikonins may have clinical potential as anti-inflammatory therapeutics.  (+info)

Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant. (63/339)

PURPOSE: To evaluate the feasibility of a nonbiodegradable polymeric episcleral implant as a new controlled intraocular delivery system of betamethasone (BM) to the posterior pole of the eye. METHODS: The episcleral implant, which is composed of a drug-releasing component and a suture tag, released BM through an ethylene vinyl acetate membrane. The implants were placed on the sclera in 12 eyes of 12 Japanese white rabbits so that the drug-releasing surface could attach to the sclera at the posterior pole. BM concentrations in the aqueous humor, vitreous, and retina-choroid (posterior half and anterior half) were determined by high-performance liquid chromatography (HPLC) at weeks 1, 2, and 4 after implantation. In addition, the intraocular tissue distribution of the drug was evaluated by fluorescein microscopy after implantation of the implant loaded with 6-carboxy fluorescein diacetate (6-CFDA) as a drug marker. Retinal toxicity was evaluated by electroretinography and histologic examination. RESULTS: The implant showed zero-order release profiles both in vitro and in vivo for 4 weeks. BM concentrations in the retina-choroid after implantation were maintained above the concentrations effective for suppressing inflammatory reactions for at least 4 weeks. The BM concentration was greater in the posterior half of the retina-choroid than in the vitreous. It was confirmed that 6-CFDA penetrated through the sclera and dispersed into the retina-choroid. Fluorescence from 6-CFDA gradually decreased in intensity with increased distance from the implantation site. Electroretinography and histologic study showed no substantial toxic reactions. CONCLUSIONS: These findings suggest that the episcleral implant may be a useful drug carrier for intraocular delivery of BM, especially for the posterior part of the eye.  (+info)

Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age. (64/339)

AIM: To investigate the pharmacokinetics and pharmacodynamics of single dose propacetamol in preterm and term infants on the first day of life. METHODS: Neonates were stratified by gestational age. Preterm (< 37 weeks) and term (37-41 weeks) infants received a single dose of propacetamol in the first 24 hours of life when they had minor, painful procedures or as additional treatment in infants receiving opioids. Blood samples were taken from an arterial line, and pain was evaluated by a multidimensional pain scale. Results were reported as mean (SD). Student's t and Wilcoxon tests were used to compare the groups. RESULTS: Thirty neonates were included, 10 of which were term infants. Serum half life was 277 (143) minutes in the preterm infants and 172 (59) minutes in the term infants (p < 0.05). Clearance was 0.116 (0.08) litre/kg/h in the preterm infants and 0.170 (0.06) litre/kg/h in the term infants (p < 0.05). Gestational age correlated with serum half life (r = -0.46). No effect of sex or administration of prenatal steroids was found on the pharmacokinetics of paracetamol. In neonates who only received propacetamol (n = 15), the level of analgesia seemed to be associated with the therapeutic (> 5 mg/l) level. CONCLUSIONS: A correlation was found between gestational age and the serum half life of propacetamol. The maturational trend of clearance and half life in preterm and term neonates is in line with data on the pharmacokinetics of propacetamol beyond the newborn period.  (+info)