Localized lipoatrophy after glatiramer acetate injection in patients with remitting-relapsing multiple sclerosis.
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Biomedical subjects
Publications and source records attributed to F Drago.
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The PGF2alpha derivative, latanoprost, is a recent anti-glaucoma drug that has been reported to induce a discrete incidence of increased iris pigmentation in men. The present experiments were made in order to study whether this phenomenon could be influenced by the tyrosinase inhibitor, alpha-methyl-p-tyrosine. Melanin content, melanin production and tyrosinase activity of cultured uveal melanocytes derived from irides of brown or brown-blue color were measured after adding latanoprost at different molar concentration with or without alpha-methyl-p-tyrosine (10(-5)m). It was shown that latanoprost stimulated melanin content, melanin production and tyrosinase activity in a molar range between 10(-7) and 10(-5)m in uveal melanocytes derived from irides of both brown and brown-blue color. The effect seemed to be more pronounced in melanocytes derived from irides of brown-blue color. The adding of alpha-methyl-p-tyrosine completely prevented latanoprost-induced stimulation of melanin production in uveal melanocytes derived from irides of both colors. These results suggest that latanoprost-induced stimulation of melanin production, follows the metabolic pathway involving tyrosinase activity and may be relevant for the therapeutic application of latanoprost in glaucoma in order to reduce its side-effect resulting in increased iris pigmentation.
Since the sexual dimorphism of gastroduodenal ulcers is well known and might possibly relate to the actions of sex hormones, we studied the role of the female sex steroids, progesterone and 17beta-estradiol in cysteamine-induced mucosal ulcers in female Wistar rats (200-220 g). Administration of cysteamine (400 mg/kg, s.c.) provoked macroscopic gastroduodenal mucosa injury as assessed planimetrically, an increase in microvascular permeability in the stomach and the duodenum as assessed by extravasation of radiolabelled albumin, and decreased gastroduodenal mucus levels as assessed by the Alcian blue technique. Ovariectomy (2 weeks before cysteamine) decreased plasma 17beta-estradiol level as assessed by radioimmunoassay, gastroduodenal macroscopic injury and albumin extravasation, and increased mucus levels following cysteamine challenge. Administration of progesterone (10-50 mg/kg/week, s.c.) attenuated in a dose-dependent manner cysteamine-induced gastroduodenal mucosa injury and microvascular leakage, while it increased mucus levels in the stomach and the duodenum. In contrast, administration of 17beta-estradiol (1-5 mg/kg/week, s.c.) dose-dependently augmented gastric and duodenal macroscopic mucosa lesions and microvascular injury provoked by cysteamine, and caused a further reduction in gastroduodenal mucus levels observed after cysteamine administration. In different experiments, ovariectomy decreased indomethacin-induced gastroduodenal injury. The injection of 17beta-estradiol (1-5 mg/kg/week) did not affect gastroduodenal damage, while treatment with progesterone (10-50 mg/kg/week) protected against indomethacin-provoked mucosa ulcers. It is concluded that female sex steroids play a role in drug-induced gastroduodenal ulcers by modulating microvascular permeability and mucus secretion.
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Amylin (AMY) is a peptide of pancreatic origin principally involved in the carbohydrate metabolism, but that may interfere with central and peripheral dopamine (DA) pathways. The peptide, injected intracerebroventricularly (ICV) at the dose of 2.5 microg/rat, induced a decrease of copulatory activity in good copulators (GCO) and sluggish (SLU) male rats. The dose of 0.1 microg/rat did not affect significantly the sexual behavior of GCO rats, whereas AMY 0.5 microg/rat increased only the latency and reduced the frequency of ejaculation. At the dose of 2.5 microg/rat AMY antagonized the activation of sexual behavior induced by the DA receptor agonist, apomorphine administered subcutaneously (SC) at the dose of 100 microg/kg. Moreover, this inhibitory effect was blocked by the calcitonin gene-related peptide and AMY receptor antagonist, CGRP (8-37) fragment (injected ICV at the dose of 1 microg/rat). These data suggest that AMY may exert inhibitory effects on male sexual behavior in rats, probably interfering with central DA neurotransmission and with CGRP receptors.
Prenatal stress may induce intrauterine growth retardation, but it is not known whether a treatment with the anxiolytic benzodiazepine, diazepam may interfere with this phenomenon. A daily physical stress consisting of a forced immersion for 15 min in cold water was applied to pregnant rats of the Wistar strain from gestational day 5 until parturition. Animals were treated either with physiological saline or with diazepam (0.1 or 1 mg/kg/day) injected intraperitoneally 1 h prior to stress application. Control animals received injections of physiological saline but were not subjected to physical stress. Newborn pups subjected to prenatal stress showed reduced body weight as compared to control animals. Offspring were also examined for the appearance day of the following reflexes: cliff aversion, startle, righting, forelimb placing, forelimb grasping and bar holding. Hair growth, and first day of ears and eyes opening was also scored. At 60 days of age, male rats from the three experimental groups were subjected to behavioural tests, i.e., constrained swim (despair test) and step-through passive avoidance response. Animals subjected to prenatal stress showed a delayed appearance of all neonatal reflexes and behavioural deficits in adulthood, namely increased immobility in the despair test and reduced retention of a passive avoidance task. The prenatal treatment with diazepam totally counteracted the effect of stress, normalizing the time-course of neonatal reflexes and the behavioural responses in adulthood. No difference was seen between the effects of the two drug doses. It is concluded that prenatal physical stress may induce body growth retardation and may be considered as a model for human intrauterine growth retardation. The treatment with an anxiolytic benzodiazepine, such as diazepam, may counteract the effects of prenatal stress interfering with the biological consequences of stress concerning probably cerebral neurotransmitters in both the unborn foetus and the pregnant rat.
The aim was to determine whether the clinical features of tachycardias originating from the right ventricular outflow tract in children with an apparently normal heart could predict the presence and the severity of the histopathological substrate. Thirteen children (median age 6 years; range 6 months-12 years) with tachycardia originating from the right ventricular outflow tract of apparently normal hearts, were assessed by echocardiography, heart catheterization with angiography, endomyocardial biopsy (13 patients) and magnetic resonance imaging (MRI) (nine patients). Tachycardia was symptomatic in six and sustained in nine. Endomyocardial biopsy and MRI revealed acute myocarditis in five patients (38%), fatty infiltration of the right ventricle in two (15%), and minor histologic abnormalities in three (23%). Myocarditis was diagnosed in three of nine patients with sustained ventricular tachycardia, as opposed to two of four with non-sustained tachycardia (p = NS); in three of six symptomatic versus two of seven asymptomatic patients (p = NS); and in two of eight patients in whom ventricular tachycardia was induced during exercise testing as opposed to one of three in which it was not inducible (p = NS). A histopathological substrate was found in six of nine patients with sustained ventricular tachycardia, and in all four with non-sustained tachycardia (p = NS); in five of six patients with symptoms versus five of seven asymptomatic patients (p = NS); and in five of eight with inducible ventricular tachycardia during exercise testing versus all three in whom it was not inducible (p = NS). The mean rate of tachycardia was 184+/-39 beats min(-1) in patients with myocarditis, as opposed to 171+/-48 in patients without myocarditis (p = NS); and 163+/-33 in patients with a histopathological substrate compared with 210+/-65 in patients without a histopathological substrate (p = NS). It is concluded that a histopathological substrate is present in the greater majority of children affected by the so-called right ventricular outflow tract tachycardia, but that the clinical features of the tachycardia do not predict the presence and the severity of this histopathological substrate.
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The protective activity of the phenylbutazone derivative, sulfinpyrazone on retinal lesions has been assessed in rabbits with severe streptozotocin-induced diabetes. Sulfinpyrazone (8 mg kg-1 per day per os) was administered in diabetic animals in two different experimental procedures: for 135 days in a preventive approach (beginning on the day of initial hyperglicaemia); and for 30 days in a therapeutic approach (beginning on the day of appearance of severe retinal damage). The drug treatment made either with the preventive or the therapeutic approach reduced the incidence of serious retinal lesions and increased that of light lesions as assessed by a biomicroscopic method. Biochemical analyses showed that experimental diabetes was accompanied by sustained decrease in glucose and pyruvate and an increase of the lactate content in the retina. A decrease of alpha-ketoglutarate and citrate and an increase of succinate were also observed along with a decrease of ATP, ADP and an increase in AMP. Either the preventive or the therapeutic approach was followed by an increased pyruvate and ATP content and decreased lactate and AMP content in the retinal tissue. It is possible that this drug acts on the retinal tissue by inhibiting platelet aggregation and protecting vasal endothelium with the consequent suppression of the release of vasoactive substances that facilitate platelet adhesion.
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The atrioventricular node is situated in the lower atrial septum, at the apex of the Koch's triangle. The dimensions of the Koch's triangle are studied in adult humans, while no data exist about them in pediatric age. The knowledge of the dimensions of Koch's triangle in childhood is very important for safe and correct application of radiofrequency energy during transcatheter ablation. The dimensions of Koch's triangle were determined in 69 human pediatric hearts. The median age of the children was 3 months, with a range from 1 day to 14 years, 30 were female and 39 were male. Relations between body weight (extracardiac parameter) and tricuspid valve diameter (intracardiac parameter) were determined in all hearts to show morphometric modifications with growth. The distribution of body weight was not Gaussian and no correlation could be obtained between Koch's triangle dimensions and body weight. However, it was possible to identify that the mean ratio between the cathetus of the Koch's triangle corresponding to the annulus of the tricuspid valve and the tricuspid valve diameter was 0.45 +/- 0.16, with a highly significant correlation coefficient (r = 0.653, P < 0.001). Therefore, by knowing: (1) the diameter of the tricuspid valve, and (2) the constant ratio between the cathetus of the Koch's triangle and the tricuspid valve diameter, it is possible to calculate the length of the segment of the tricuspid annulus along which the transcatheter application of radiofrequency current can be applied to ablate the slow-pathway, thus reducing the risks of damage of the atrioventricular node.
BACKGROUND: Concern exists in literature about the clinical course, the best acute and chronic treatment and the prognosis of idiopathic neonatal atrial flutter. The aim of our study was to evaluate this in a population of our patients with this type of arrhythmia. METHODS: Six infants (3 M, 3 F, mean age 42 +/- 62 days, range 1-150) affected with atrial flutter without structural heart disease were studied and then acutely and chronically treated. The effectiveness of chronic antiarrhythmic treatment was evaluated with Holter monitoring every 3 months for the first year of life and with transesophageal atrial pacing. RESULTS: Mean arrhythmia cycle length was 180 +/- 34 ms with atrioventricular conduction ratio ranging between 1:1 and 3:1. Two patients with clinical signs of heart failure were successfully treated with DC shock. Transesophageal overdrive atrial pacing was successfully used in one patient treated with i.v. propafenone without benefit. In the remaining three patients, cardioversion was achieved with amiodarone after digoxin had failed in all three and propafenone had failed in two of them. To prevent recurrences, we treated four patients with amiodarone, one with amiodarone combined with propranolol and one with digoxin. During the follow-up (22 +/- 11 months), neither arrhythmia recurrences nor side-effects of the therapy occurred. CONCLUSIONS: Neonatal atrial flutter is an arrhythmia with significant acute morbidity but an excellent long-term prognosis. Electrical cardioversion is the first-choice treatment when the arrhythmia is not well-tolerated hemodynamically, while class III antiarrhythmic drugs such as amiodarone should be preferred in the other cases.