Ryba M

The application of microspheres from the copolymers of lactide and ϵ-caprolactone to the controlled release of steroids

Abstract The microspheres made of the copolymers of lactide and ϵ-caprolactone were used for the controlled release of progesterone and β-estradiol. The copolymers contained 83–94% of l or d,l -lactide. The influence of the microstructure of lactidyl blocks in the copolymer chains on the drug release rate was studied. More uniform release rate was observed in the case of the copolymer derived from d,l -lactide as composed to l -lactide. For the copolymer containing 83–94% of d,l -lactide units the progesterone and β-estradiol release rate in vitro was found to be practically constant within over 40 days. The in vivo studies performed on rats revealed that the period of constant release rate of β-estradiol can be prolonged to about 70 days. The microspheres made of the applied poly-( d,l -lactide-co-ϵ-caprolactone) are the convenient system for long time release of steroids.

Oral coenzyme Q10 administration prevents the development of ischemic brain lesions in a rabbit model of symptomatic vasospasm

Abstract Treatment with oral coenzyme Q10 (CoQ10, 10 mg/kg per day for 6 days) was compared with no treatment in a previously described rabbit model of symptomatic cerebral vasospasm [Endo et al. (1988) Stroke 19: 1420–1425]. The treatment was initiated within 1–2 h after injection of autologous blood into the subarachnoid space. In CoQ10-untreated rabbits, moderate to severe neurological deficits developed, and multiple focal ischemic lesions were found in the brain regions with compromised blood supply, i.e., in the regions normally supplied by common carotid arteries which are subject to ligation in this model. CoQ10 treatment prevented the development of both the neurological deficits and histologically detectable brain tissue damage. In both CoQ10-treated and -untreated rabbits, infiltration of mononuclear cells was evident in the brain stem, although this region did not show signs of ischemic damage. The findings indicate that the histological and neurological correlates of brain tissue damage in this rabbit model of symptomatic cerebral vasospasm develop via mechanism(s) involving free radical-mediated oxidation of plasma lipoproteins. Similar mechanisms may play a role in the development of brain damage attributed to cerebral atherosclerosis.

Effect of parenteral cladribine on relapse rates in patients with relapsing forms of multiple sclerosis: results of a 2-year, double-blind, placebo-controlled, crossover study

Objective This randomized, 2-year, double-blind, placebo-controlled, crossover study evaluated cladribine for relapsing forms of multiple sclerosis. Design Patients (n = 84) received seven 5-day courses of subcutaneous cladribine at 5 mg/day (group A) or placebo (group B) in year 1; treatment was reversed in year 2. Results Cladribine was well tolerated and associated with a favorable safety profile. Mean Expanded Disability Status Scale scores remained stable. In group A, mean relapse rates were 0.15 in year 1 (cladribine) and 0.42 in year 2. In group B, relapse rates were 0.61 in year 1 and 0.50 in year 2 (cladribine). Patients required fewer steroid courses during cladribine periods. The therapeutic efficacy of cladribine was associated with a sustained reduction in lymphocyte count.

Changes in amyloid precursor protein and apolipoprotein E immunoreactivity following ischemic brain injury in rat with long-term survival : influence of idebenone treatment

We observed in extra- and intracellular space accumulation of different fragments of amyloid precursor protein (APP) and apolipoprotein E (Apo E) in rat brain after cardiac arrest with long-term survival. Idebenone treatment did not affect APP and Apo E alterations in this condition.

2-Chloro-2′ deoxyadenosine prevents angiopathic changes in cerebral arteries in experimental SAH in rabbits

SummaryWe compared the morphology of the basilar artery walls in rabbits with experimental subarachnoid haemorrhage (SAH) without and with concomitant treatment with a novel immunosuppressive drug, 2-chloro-2′-deoxyadenosine (2 CdA). The treatment was successful in the prevention of the angiopathic changes, most likely due to its ability to inhibit lymphocyte activation in response to mitogenic signals. Since lymphocyte (and monocyte?) activation may play an important role in the development of the delayed neurological deficits in patients following SAH, the use of 2 CdA to prevent these deficits shall be considered.

Disturbed Patency of the Upper Airway and Its Consequences

Every ENT (Ear, Nose and Throat) surgeon meets many patients, both adults and children, suffering from disturbances of upper airway patency. Usually the obstruction is at the level of the nose, nosopharynx or pharynx (Guilleminault et al.,1976). Disturbed patency of the upper airway due to the hypertrophy of tonsills or adenoid is discussed in another paper (Skartyhski et al., this volume). Separate discussion is needed, concerning the problem of nasal airway compromise in patients with sleep apnea syndrome. In this paper we present the consequences of chronic upper airway compromise. A typical patient with mild obstruction of the airflow in the upper respiratory routes presents himself to an otolaryngologist after many years of unsuccessful treatment performed by cardiologists, neurologists or psychiatrists. Not before the authors working on the problem of disturbances of breathing during sleep have proposed a new syndrome in otorhinolaryngology, such patients were fully diagnosed and treated (Simmons and Hill, 1974). The basic examination is an all-night monitoring of many parameters of the blood and functions of the organism — a polysomnographic study (PSG). In patients with upper airway compromise PSG reveals many pathologies in circulatory system function (Orr and Shappell, 1975; Lugaresi et al., 1980) namely the increase in blood pressure and lung circulation, disturbances of the heart rhythm and significant changes in ST — T in ECG examination. Retrospective epidemiologic studies confirmed more frequent pathology in circulatory system in the patients with apneas during sleep. It is possible that sleep apnea may be one of the etiologic factors of the hypertension and of some of the heart diseases (Lugaresi et al., 1980; Miller, 1982).