Changes in asthmatic patients' symptoms and lifestyles on institution of inhaled budesonide therapy

An open, multi-centre, general practice study was carried out in 1661 asthmatic patients to assess the efficacy, in terms of symptom relief and changes in lifestyle, of budesonide and to record objective lung function changes and any adverse events. After a 1-week run-in period on any pre-trial anti-asthma medication, patients received either 200 micrograms or 400 micrograms budesonide twice daily by metered dose inhaler for 4 weeks. Peak expiratory flow rate (PEFR) was measured by the doctor on entry, after the run-in, and at the end of the study and patients were asked to complete diary cards on a daily basis to record compliance, bronchodilator usage and the severity of cough, wheeze and sleep disturbance, and weekly to record 5 lifestyle assessments, e.g. physical activity. Analysis of data from the clinic visits and 1375 completed diary cards showed that PEFR increased significantly from 321 +/- 3 l/min at the end of the run-in to 368 +/- 3 l/min at the end of the trial; 77% of patients had an improved PEFR. Bronchodilator use decreased significantly from 4.2 +/- 0.1 times/day during the run-in period to 3.0 +/- 0.1 times/day at the end of the study; 65% of patients used less bronchodilator. Significant improvements were recorded in all the symptoms and lifestyle indices monitored; 76% of patients improved in at least 5 of the 11 assessments. Treatment-emergent adverse events occurred in 103 (6%) of patients: none was classified as serious or unexpected. No sub-group of patients was identified in which the results were at variance from the full sample. It is concluded that budesonide improves patients' lifestyle and ability to carry out normal activities, as well as improving PEFR and reducing bronchodilator use, in mild to moderately severe asthmatics treated in general practice.     

Development of an intravenous desferrioxamine mesylate treatment protocol for swine: monitoring of desferrioxamine and metabolites by high-performance liquid chromatography

Desferrioxamine (DFO) metabolism and its pharmacokinetics were studied in a swine model using high-performance liquid chromatography. DFO and three iron-binding metabolites occurred in plasma. Interindividual differences in pharmacokinetics and metabolism were observed. Urine analysis in 4 pigs showed three iron-binding metabolites. The mean percent dose excreted in urine in the form of the parent drug was 45 +/- 10% and 10 +/- 2% (means +/- SD) in the form of metabolites. Of the total amount of the parent drug infused, 3 h after initiation, 87% was in the form of DFO, whereas 13% was present as the DFO-iron III complex which represented 45 mg of urinary iron elimination. The described DFO infusion protocol provides for sufficient DFO to chelate significant amounts of ferric iron in excess of normal levels, thus allowing experimental studies of iron chelation in a variety of disease states.     

Antihepatotoxic Effects of chlorogenic acid from Anthocephalus cadamba

In the present study, chlorogenic acid (CGA) isolated from Anthocephalus cadamba was screened for hepatoprotective activity by in vitro and in vivo assay methods using carbon tetrachloride (CCl₄) as a model of liver injury. Intraperitoneal administration of CGA to mice at a dose of 100 mg/kg body weight for 8 days caused significant reversal in lipid peroxidation, enzymatic leakage, cytochrome P450 (Cyt P450) inactivation and produced enhancement of cellular antioxidant defence in CCl₄-intoxicated mice, revealing that the antioxidative action of CGA is responsible for its liver protective activity. CGA exhibited a better therapeutic protective action than silymarin (SM), in CCl₄-administered mice.     

3β-Hydroxysteroid Dehydrogenase/Isomerase and Aromatase Activity in Primary Cultures of Developing Zebra Finch Telencephalon: Dehydroepiandrosterone as Substrate for Synthesis of Androstenedione and Estrogens

3β-hydroxysteroid dehydrogenase/Δ⁵−Δ⁴isomerase (3β-HSD) activity was measured in primary dissociated cell cultures prepared from telencephalons of developing zebra finches. 3β-HSD activity was confirmed after cultures were incubated with [7-³H]pregneno- lone (Preg) or (1,2,6,7-³H-) dehydroepiandrosterone (DHEA) and³H-progesterone (Prog) and³H-androstenedione (AE) were detected in the medium. Product identity was confirmed by recrystallizations and by HPLC analysis. When DHEA was used as substrate,³H-estradiol and³H-estrone were also detected in the culture medium, presumably derived from the aromatization of³H-AE or³H-T produced from³H-DHEA. To test this idea, cultures were incubated with³H-DHEA together with radioinert AE or with fadrozole HCl, a potent and specific aromatase inhibitor. In the presence of radioinert AE,³H-AE increased but metabolites of³H-AE decreased in the media; in the presence of fadrozole,³H-estrogens decreased but³H-AE and its androgenic metabolite³H-5β-androstanedione increased. These data demonstrate 3β-HSD activity in the songbird brain. The presence of Prog and estradiol in these cultures suggest that Preg and DHEA can potentially serve as substrates for the ultimate formation of active sex steroids in the songbird telencephalon.     

Late, Painful, Subungual Hyperkeratosis in Incontinentia Pigmenti

Abstract: The postpubertal appearance of subungual, painful keratotic tumors is a rare feature of incontinentia pigmenti. A patient affected by incontinentia pigmenti developed subungual, painful, nontumoral, hyperkeratotic lesions of the hands at 10 years of age. The mildness of the subungual lesions may be explained by the early stage of the disorder, but it is difficult to correlate the severity of the fingertip pain with the absence of true tumoral swelling. To our knowledge this is the youngest patient reported so far and the only one with a prepubertal expression of this puzzling disorder.     

Treatment of pyoderma gangrenosum

Critical to the proper management of pyoderma gangrenosum are correct diagnosis, identification and treatment of any underlying disorder, and the proper choice of topical and systemic therapy. Many agents are available for the treatment of pyoderma gangrenosum. We review the current therapeutic options, their efficacy and side effects, and we offer some guidelines for their proper selection.     

Reverse enhancement of hemorrhagic brain lesions on postcontrast MR: detection with digital image subtraction.

PURPOSETo investigate the decrease in signal intensity on T1 - weighted MR images of some hemorrhagic intracranial lesions after administration of contrast material.METHODSPostprocessing digital image subtraction was performed in 16 MR studies (13 patients) of lesions that showed hyperintensity on noncontrast T1-weighted images. Repetition time and echo time were identical for all precontrast and postcontrast studies. Regions of interest were measured in each lesion, contralateral white matter, and background (before and after contrast enhancement).RESULTSIn six of 16 MR studies, a significant net decrease in signal intensity was seen within the hemorrhagic lesion after contrast enhancement (reverse enhancement). All the lesions were hematomas within residual or recurrent malignant tumors.CONCLUSIONSDigital image subtraction confirms the existence of reverse enhancement. This phenomenon is due to the combined T2-shortening effects of two paramagnetic substances, methemoglobin and gadolinium, which cause the signal reduction produced by the T2 effects to occur at lower concentrations of gadolinium.     

Long Fibre Growth by Axons of Embryonic Mouse Hippocampal Neurons Microtransplanted into the Adult Rat Fimbria

We have described a method for the microtransplantation of a suspension of a few thousand cells from mid to late embryonic mouse hippocampi into the fimbria of immunosuppressed adult rat hosts. There was close graft-to-host contact, across a non-scarred interface. The transplanted cells included CA3 type pyramids, and were enclosed within the host myelinated fibre tract, whose glial framework was largely undisturbed. Immunohistochemistry of two species-specific markers (M6 and Thy-1.2) showed that the donor mouse neurons grew fine (<0.5 μm diameter) axons which extended singly or in fascicles through the rat host fimbria for a maximum distance of at least 10 mm. The donor axons were intimately integrated among and closely aligned to the host tract axons and to the interfascicular glial rows of the host tract. The axons travelled (i) laterally through the ipsilateral fimbria, (ii) medially across the midline in the ventral hippocampal commissure to reach the contralateral fimbria and alveus, and (iii) rostro-medially to the septum. On approaching the terminal fields appropriate to hippocampal CA3 pyramidal cell axons, the transplant axons gave rise to fine preterminal branches which were continuous with a reticular or amorphous immunoreactivity in the stratum oriens and stratum pyramidale of the ipsilateral hippocampus, and in the lateral and triangular septal nuclei. The donor axons extended along the host fimbria at a rate of ∼ 1 mm per day, reaching their terminal field destinations by ∼1–2 weeks. At 7 weeks the projections were maintained, but with little further extension. These observations indicate that the microenvironment of myelinated adult fibre tracts is permissive for an abundant and rapid growth of axons from transplanted embryonic cell suspensions. These axons can leave host tracts to invade appropriate terminal fields.     

Nerve growth factor and p75NGFR factor receptor mRNA change in rodent CNS following stress activation of the hypothalamo-pituitary-adrenocortical axis

The synthesis of nerve growth factor (NGF) by the hippocampus raises the possibility that NGF may play a role in the regulation of the hypothalamic-pituitary-adrenal axis (HPAA). Subchronic cold stress has been shown to activate the HPAA in a mild noninvasive manner, to stimulate serum glucocorticoid levels, and to perturb NGF binding in hippocampus and basal forebrain. One or repeated episodes of cold stress increased NGF mRNA levels in the hippocampus and p75^NGFR mRNA levels in the basal forebrain. These changes were not due to elevated serum glucocorticoid levels since treatment with exogenous corticosterone had no effect on NGF and p75^NGFR mRNA levels. Adrenalectomy did not prevent the stress induced increases in NGF and p75^NGFR mRNA. © 1993 Wiley-Liss, Inc.