Growth in children with steroid sensitive nephrotic syndrome

Background: Nephrotic syndrome in children usually has an onset between 2–8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS).     

Inhibition of noradrenaline uptake 2 in the isolated rat heart by steroids, clonidine and methoxylated phenylethylamines

Various steroids (corticosterone, testosterone, progesterone, β-oestradiol) produced a dose-dependent inhibition of the uptake of ³H-noradrenaline by the uptake₂ mechanism in the isolated perfused rat heart. These compounds were potent and selective inhibitors of uptake₂, with the exception of β-oestradiol which also inhibited noradrenaline accumulation in sympathetic nerves by the uptake₁ mechanism. The hypotensive drug, clonidine, was a moderately potent and highly selective inhibitor of uptake₂. Uptake was also inhibited by certain methoxylated phenylethylamine derivatives, but was unaffected by cocaine, desipramine, amitriptyline, angiotensin, histamine, ethanol or prostaglandins.     

Intravenous administration of alendronate counteracts theIn vivo effects of glucocorticoids on bone remodeling

The purpose of the investigation was to test the use of alendronate in the therapy of children affected by chronic rheumatic diseases and symptomatic drug-induced osteoporosis. Two courses of alendronate were intravenously administered to four girls with vertebral fractures that were glucocorticoid induced. Improvement of back pain and bone mineral density increase evaluated by DXA and conventional spine X-rays were observed. Our study supports the ABD-induced improvement of the negative effects of long-term therapy on bone mineral density in children with chronic rheumatic diseases.     

The incorporation and utilization of radiolabelled lipids by adult Schistosoma mansoni in vitro

Live adult Schistosoma mansoni, maintained in vitro were able to absorb and utilize radiolabelled arachidonic acid, linolenic acid, 3-sn-phosphatidylcholine, tripalmitylgylcerol and cholesterol in the culture medium. Differential centrifugation demonstrated that all these lipids were incorporated into the parasite's various membrane structures. Analysis by thin-layer chromatography of the labelled compounds which resulted from incubation with the labelled lipids revealed that arachidonic acid, linolenic acid and fatty acids of tripalmitylglyceron and 3-sn-phosphatidylcholine was present largely as triacylglycerol with smaller amounts of labelled diacylglycerol, phospholipids and fatty acids. The labelled polar head group of 3-sn-phosphatidylcholine was cleaved from the molecule during incorporation, which suggested that hydrolysis of complex lipids is an integral part of the absorption mechanism. Cholesterol was not apparently altered during incorporation or further metabolized. It was also observed that arachidonic acid was incorporated more readily than the other lipids, however, no prostaglandin biosynthesis was detected.     

Corticosteroids and Tamsulosin in the Medical Expulsive Therapy for Symptomatic Distal Ureter Stones: Single Drug or Association?

OBJECTIVES: To assess the clinical role of corticosteroids in the medical expulsive therapy of symptomatic distal ureteral stones. METHODS: Between January 2004 and September 2005, 114 patients with symptomatic distal ureteral stones with a >/=5mm diameter were enrolled in this prospective study and divided into four groups based on the urologist (of four) who treated them in the emergency unit. Group A (33 patients) received tamsulosin (0.4mg daily), group B (24 patients) received deflazacort (30mg daily), group C (33 patients) received both (0.4mg tamsulosin+30mg deflazacort daily), and control group D (24 patients) received only analgesics. The treatment duration was 10 d to prevent the side-effects of prolonged corticosteroid therapy. The end points were the expulsion rate, analgesic consumption, number of ureteroscopies, and safety. RESULTS: The groups were comparable in terms of age, sex, and stone location. The stone diameter was 5.96+/-0.33mm for group A, 5.83+/-0.4mm for group B, 5.88+/-0.23mm for group C, and 5.71+/-0.5mm (p>0.05) for group D. The rates of expulsion for the four groups were 60%, 37.5%, 84.8%, and 33.3%, respectively. There was a significant difference between group C and the other groups (p<0.001). The mean analgesic consumption was 42.5+/-0.4mg for group A, 50+/-0.3mg for group B, 27.3+/-0.5mg for group C, and 81+/-0.33mg for group D, with a significant difference between group C and the other groups (p<0.001). During the treatment period, only two cases of drug side-effects related to tamsulosin (without any drop-outs) were recorded. CONCLUSION: When the medical expulsive therapy for symptomatic distal ureteral stones is considered, the use of steroids (deflazacort) proves efficient only when administered together with alpha(1)-blockers (tamsulosin). In addition, tamsulosin used on its own as a medical expulsive therapy can be considered as an alternative treatment for those patients who are not suitable for steroid therapy, as it is generally efficient.     

Risk-Benefit Assessment of Fluticasone Propionate in the Treatment of Asthma and Allergic Rhinitis

Benefits

Fluticasone propionate (FP) is a new topical corticosteroid spray for the treatment of allergic rhinitis and asthma. FP has been shown to be effective for the treatment of adult and pediatric asthma, even at rather low doses (25 μg twice daily [b.i.d.]); many studies in asthma have shown clinical efficacy of fluticasone at half the dose of the comparison steroid (such as beclomethasone dipropionate [BDP) or budesonide [BUD]). However, exact dose comparisons cannot be made because dose-ranging comparison studies have not been done. Studies in allergic rhinitis in children and adults have shown good efficacy in FP-treated patients at a dose of 200 μg once daily (o.d.), intranasally. In summary, FP is effective in both asthma and allergic rhinitis.

Risks

FP has minimal systemic activity because the portion of drug that is swallowed is not absorbed from the gut. Thus, the amount available for systemic activity is only that which is absorbed through the nasal mucosa (in the treatment of rhinitis) or through the alveoli of the lungs (in the treatment of asthma). When laboratory assays of adrenal function or bone formation are measured, FP and other inhaled corticosteroids can be shown to cause suppression of these markers, especially at high doses. There have been no consistent reports of clinical adrenal suppression or osteoporosis caused by FP.

In summary, the risk-benefit ratio of FP at the usual doses (therapeutic ratio) is very favorable. High doses may show evidence of suppression of the hypothalamic pituitary axis as measured by in vitro tests, but evidence of corresponding clinical adverse effects is lacking.     

Plasmapheresis in Severe Forms of Myasthenia Gravis

In this study we introduce a new combination treatment of plasma exchange (PE) and high daily doses of prednisone for severe forms of myasthenia gravis (MG). The clinical efficacy of the combined therapy has been tested in 18 patients suffering from severe forms of MG. The protocol included 5 sessions of PE, performed in a range of 15 days, 1 session every 3 days, with concurrent administration of oral prednisone (1 mg/kg of body weight), starting at the first session of PE and given daily for at least 3 months. At the end of the entire cycle of PE, almost complete recovery (more than 90% of the initial clinical score) was obtained in 8 of 18 patients while an improvement between 60 and 90% of the initial score was achieved in 9 of 18 patients. An early improvement was noted 24 h after the beginning of plasmapheresis in 11 of 18 patients. No recurrence of symptoms was reported after 36 months of follow-up for 17 patients. The administration of steroid therapy was never followed by an early exacerbation of myasthenic symptoms as reported when it is administered in the absence of concomitant PE. According to our results, we can conclude that high doses of oral prednisone therapy in simultaneous association with PE lead to successful control of severe forms of MG, significantly superior to the therapeutic strategies until now adopted and reported in literature.     

Ethanol Modulates the Hormone Secretory Responses Induced by Epidermal Growth Factor in Choriocarcinoma Cells

Analysis of clinical data has implicated ethanol (EtOH) as an embryotoxic agent and as an agent that disrupts normal placental structure and function. Because epidermal growth factor (EGF) is an important regulator of placental function, we have studied the effects of EtOH on EGF-induced hormone secretion using JEG-3 choriocarcinoma cells that serve as a model for trophoblast cells. EtOH at physiological (5-100 m m ) concentrations modulated effects of EGF in a time and dose-dependent manner. EGF-induced P₄ secretion was increased by 20–100 mM EtOH after a 2-day pretreatment of cells with EtOH, but not after a 6-day pretreatment. Preincubation with 50 mM EtOH doubled the P₄ responses to 50 and 100 ng/ml EGF. Although a 2- or 4-day preincubation of cells with 10–50 mM EtOH increased the secretion of E₂ in response to 20 ng/ml EGF, a 6-day preincubation inhibited the secretory response to EGF. Pretreatment of cells with 10–50 m m , but not 100 m m EtOH for 2 to 6 days enhanced the human chorionic gonadotropin (hCG) secretory response to EGF. At 50 mm EtOH, the secretion of hCG in response to EGF was increased 2-fold. EtOH also increased basal hCG secretion in a dose-dependent manner between 10–50 m m EtOH. These results suggest that EtOH may modulate EGF-stimulated hormone secretion from cells of placental origin. Such alterations, if they occur in vivo, may impact on the function of the placenta and could potentially explain the pathophysiology of alcohol toxicity during pregnancy.