Pharmaceutical availability of betamethasone dipropionate and gentamicin sulfate from cream and ointment.
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Kinetics of drug release from both compared preparations occuring as a cream and ointment, was in vitro studied. A reversed-phase HPLC method was developed for the determination of betamethasone dipropionate in lipophylic bases. Analyses were performed using a PLRP column with a mobile phase of methanol-acetonitrile-water and ultraviolet detection at lambda = 254 nm. The calibration curve was constructed for concentration (.0-50.0 microg/ml. The method is simple, accurate and precise. For the determination of gentamicin sulfate the FPIA method was used. (+info)
Repeated maternal glucocorticoid administration and the developing liver in fetal sheep.
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Prenatal glucocorticoid exposure has been associated with a reduction in birth weight and postnatal alterations in glucose homeostasis and hypothalamic-pituitary-adrenal (HPA) axis function. The mechanisms underlying these responses are unknown, although changes in fetal hepatic development may play an important role. The fetal liver produces key regulators of fuel metabolism and of the developing HPA axis that are altered by glucocorticoids. The local availability of glucocorticoids is regulated, in part, by corticosteroid-binding protein (CBG), glucocorticoid receptors (GR) and by the enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD), but the effects of maternal glucocorticoid administration on the expression of these genes in the fetal liver are unknown. 11betaHSD1 is the predominant form of this enzyme present in the liver and is responsible for the conversion of cortisone to cortisol. To determine if prenatal glucocorticoid exposure alters fetal hepatic regulation of CBG, 11betaHSD1 and GRs, we treated pregnant ewes with betamethasone (0.5 mg/kg) intramuscularly at 104, 111 and 118 days of gestation (term 150 days). Animals were killed at 125 or 146 days of gestation. Maternal betamethasone administration did not alter mean cord plasma glucose but significantly decreased cord plasma insulin levels (P<0.05) at 125 days of gestation. At 146 days of gestation, cord plasma glucose levels were significantly increased without alterations in insulin levels following maternal betamethasone treatment (P<0.05). Maternal betamethasone administration resulted in a significant increase in fetal hepatic 11betaHSD1 mRNA and protein levels at 125 days of gestation (P<0.05). CBG mRNA levels were significantly elevated over control at 125 days although levels of CBG protein were not significantly different. GR protein levels were not statistically different at either 125 or 146 days of gestation following glucocorticoid administration. These data suggest that prenatal betamethasone exposure in the ovine fetus results in alterations in cord glucose and insulin levels as well as alterations in hepatic 11betaHSD1 mRNA and protein expression. These changes in 11betaHSD1 increase the potential to generate local cortisol from circulating cortisone. We speculate that this could affect expression of glucocorticoid-dependent hepatic enzymes involved with the regulation of glucose production and HPA responsiveness. (+info)
Improving delivery and offspring viability of in vitro-produced and cloned sheep embryos.
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Recently developed, assisted reproductive technologies (e.g., in vitro embryo production and nuclear transfer) have encountered perinatal morbidity/mortality of the offspring produced, which are likely to hinder the application of these techniques. Consequently we have sought to develop a system of hormonal stimulation that will ensure the delivery of offspring more prepared for extrauterine life. Here we examine deliveries outcome in sheep carrying in vitro-produced and nuclear transfer (NT) embryos in comparison to artificially inseminated and naturally mated control ewes. All groups (excluding NT, which received one treatment) were subjected to one of two hormonal treatments for induction of delivery, whereas the third part of each group was left without any treatment. The first (commonly used for naturally mated ewes) dexamethasone treatment did not solve a majority of parturition disturbances, and actually the number of deliveries necessitating assistance was reduced (P < 0.05) by this treatment in the control group. On the other hand, combined estradiol plus betamethasone stimulation (E + B) solved a majority of complications regarding delivery performance such as lack of the preparation of the mammary gland, low myometrial contractility, insufficient cervical ripening, and impaired maternal behavior. Moreover, substantial reduction of neonatal mortality was observed following the combined treatment. In conclusion, the E + B induction of delivery overcame the majority of physiological and behavioral intrapartum failures of sheep foster mothers and increased the survival of offspring, and thus can be recommended as a safe method for inducing delivery in foster mothers carrying in vitro-generated embryos. (+info)
Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs.
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Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 +/- 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1beta mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids. (+info)
Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia.
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We present a patient with a Philadelphia chromosome positive (Ph+) acute lymphocytic leukaemia (ALL) refractory to standard induction chemotherapy. Treatment with the ABL-specific tyrosine kinase inhibitor STI571 (Glivec, Gleevec, imatinib mesylate) resulted in a complete haematologic and cytogenetic remission. Allogeneic stem cell transplantation from an unrelated donor could be undertaken while the patient was in STI571-induced complete remission from the leukaemia. At present, the patient has a 15-month post-transplantation follow-up and is in stable molecular remission as evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for the BCR/ABL fusion gene transcript. Our case demonstrates that STI571 can act as a bridge to potentially curative allogeneic stem cell transplant in otherwise poor prognosis Ph+ ALL. (+info)
Management of guttate and generalized psoriasis vulgaris: prospective randomized study.
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AIM: To assess the efficacy of betamethasone dipropionate 0.05% cream plus ultraviolet B (UVB) radiation with and without additional penicillin therapy in the treatment of guttate psoriasis, and to compare the efficacies of oral psoralen plus ultraviolet A (PUVA) therapy and systemic retinoids therapy for treatment of generalized psoriasis. METHODS: Sixty patients with guttate (n = 20) and generalized psoriasis vulgaris (n = 40) of various intensity and duration treated at the Department of Dermatology, Medical School in Skopje, from February 2000 to January 2002, were included in this prospective, open-label, randomized, parallel group study. The clinical features of the patients were quantified according to the mean psoriasis area and severity index (PASI) values. Student s t-test for paired samples and two independent samples were used in statistical analysis. RESULTS: The final PASI values were not significantly different for the patients receiving different treatments of guttate psoriasis or generalized psoriasis. The initial PASI values for guttate psoriasis patients treated with betamethasone dipropionate plus UVB with and without penicillin treatment (5.7 +/- 2.1 and 5.9 +/- 2.5, respectively) declined to 0.5 +/- 0.8 and 1.0 +/- 0.9, respectively, after the therapy. The initial PASI values in generalized psoriasis patients receiving PUVA dropped from 24.1 +/- 3.6 to 1.7 +/- 1.5 by the end of the therapy. Finally, pre-treatment PASI values in patients with generalized psoriasis receiving retinoids decreased from 24.6 +/- 3.5 to 0.9 +/- 1.1 after treatment. However, patients receiving systemic retinoids for generalized psoriasis had statistically higher incidence of side effects than patients receiving PUVA therapy (t = 6.458, df = 38, p < 0.001). CONCLUSION: Penicillin should be applied in addition to local corticosteroids with UVB in the treatment of guttate psoriasis, since the disease may be triggered by a streptococcal infection. In cases of generalized psoriasis vulgaris, PUVA therapy caused fewer side effects than did systemic retinoids. (+info)
Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate.
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PURPOSE: To evaluate the feasibility of using a biodegradable intrascleral implant for intraocular sustained delivery of betamethasone phosphate (BP). METHODS: The intrascleral implant (0.5 mm thick and 4 mm in diameter) was made of poly(DL-lactide) containing 25% betamethasone phosphate. The in vitro release of BP from the implant was evaluated by high-performance liquid chromatography (HPLC). The implants were placed into a scleral pocket in the rabbit's eye. The concentrations of BP in the aqueous humor, vitreous, and retina-choroid were measured by HPLC. The toxicity and biocompatibility of the implant were evaluated by slit lamp examination, electroretinography, and light microscopy. RESULTS: In vitro studies demonstrated that the implants released BP in a biphasic pattern for at least 8 weeks. The BP concentrations in the vitreous and the retina-choroid remained within the concentration range capable of suppressing inflammatory responses for more than 8 weeks. The BP concentration was greater in the retina-choroid than in the vitreous. In the aqueous humor, BP was below the detection limit during the observation period. No significant toxicity to the retina was observed. Also, the implant showed good biocompatibility in the eye. CONCLUSIONS: These results suggest that the intrascleral implant would be a promising system for delivery of steroid to the posterior segment of the eye. (+info)
Glucocorticoid exposure at the dose used clinically alters cytoskeletal proteins and presynaptic terminals in the fetal baboon brain.
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Glucocorticoids have been used for 30 years to accelerate fetal lung maturation in human pregnancy at risk of preterm delivery. Exposure to inappropriate levels of steroid, however, leads to altered maturation of the cardiovascular, metabolic and central nervous systems. The effects of betamethasone on neuronal development and function were determined in the fetal baboon brain by examination of cytoskeletal microtubule associated proteins (MAPs) and the presynaptic marker protein synaptophysin. At 0.73 gestation, commencing 28 weeks of gestation, pregnant baboons received four doses of saline (n = 8) or 87.5 microg (kg body weight)(-1) betamethasone I.M. (n = 7) 12 h apart. This dose is equivalent to 12 mg betamethasone administered daily over two consecutive days to a 70 kg woman. Baboons underwent Caesarean section 12 h after the last injection. Paraffin sections of the fetal neocortex and the underlying white matter were labelled immunohistochemically against MAP1B, MAP2abc, MAP2ab and synaptophysin and stained histochemically with hematoxylin-eosin and silver. Tissue staining was quantified morphometrically. Betamethasone exposure resulted in decreased immunoreactivity (IR) of MAP1B by 34.3 % and MAP2abc by 34.1 % (P < 0.05). Loss of MAP2 IR was due to loss of IR of the juvenile isoform MAP2c (P < 0.05). MAP1B and MAP2c are involved in neuritogenesis and neuronal plasticity. Synaptophysin IR was reduced by 51.8 % (P < 0.01). These changes might reflect functional neuronal disturbances because they were not accompanied by an alteration of the density of neurofibrils or neuronal necrosis. These results are in agreement with earlier findings of alterations of cytoskeletal proteins and presynaptic terminals in the fetal sheep brain after betamethasone infusion directly to the fetus and support a common effect of inappropriate fetal exposure to glucocorticoids on neuronal cytoskeleton and synapses in mammalian species. (+info)