Resorbed polymeric sponge used as a carrier the therapeutic substance. Part 1. Gelatine sponge.

The obtaining of porous, elastic gel matrix, as a carrier of therapeutic substance, with long decomposition time was the aim of the research. The gelatin extracted from pig skin (Fisher Chemicals Schweiz) and 86% glycerol (Chempur) was used in experiments. The studies showed that such biopolymer as gelatine enable to prepare the matrix which can remain in an organism for a time long enough and a porous structure of the sponge allows to increase absorbing capacity of exudate.     

Limited usefulness of the PFA-100 for the monitoring of ADP receptor antagonists--in vitro experience.

We have evaluated the usefulness of the PFA-100 system (collagen/ADP and collagen/epinephrine cartridges) to assess the in vitro effects of a few platelet function inhibitors: Aspisol (60 microg/ml), 4-[4-[4-(aminoiminomethyl]-1-piperazinyl]-1-piperidineactetic acid, hydrochloride trihydrate (GR144053F, fibrinogen receptor antagonist, 100 nM), adenosine-3',5'-diphosphate (A3P5P, P2Y1 ADP receptor antagonist, 500 microM) and Bis[(adenosine-5'-O-phosphorodithioyl)methylene]-phosphinic acid (APTMPA, P2Y12 ADP receptor antagonist, 500 microM) on platelet function, as compared with the other commonly used diagnostic technique, a whole blood electrical aggregometry (20 microM ADP or 0.5 mM arachidonic acid). The in vitro studies were carried out on a group of 38 subjects. Whereas all the examined platelet antagonists and inhibitors almost completely blocked the 20 microM ADP- or 0.5 mM arachidonic acid-induced (in the case of acetylsalicylic acid) whole blood aggregation, only two inhibitors (Aspisol and GR144053F) remained effective in a significant prolongation of the PFA-100 occlusion time. Otherwise, using the PFA-100 system we were not able to detect the inhibitory actions of ADP receptor antagonists- P2Y1 and P2Y12. Our findings point to a limited usefulness of the PFA-100 system for the monitoring of the effectiveness of ADP receptor antagonists. The outcomes of this study show that platelet aggregometry in whole blood is characterised by the highest sensitivity in the monitoring of the investigated blood platelet inhibitors.     

Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment

Despite years of research, delayed cerebral vasospasm remains the feared complication of a ruptured intracranial aneurysm. Worldwide effort has led to many promising experimental treatments that reverse or prevent cerebral vasospasm but none were confirmed to be effective in clinical trials. There are several sources for this failure: (1) the pathophysiology of delayed cerebral vasospasm remains poorly understood, (2) many experimental models of subarachnoid hemorrhage (SAH) do not mimic the actual clinical entity, and (3) many researchers erroneously extrapolate the data of peripheral and cerebral vascular physiological responses to the post-SAH situation. Thus, to explain the uniqueness of vasospasm and to address nitric oxide (NO) involvement in delayed vasospasm development, the following issues are addressed in this paper: (1) pathophysiological mechanisms of vasospasm, (2) NO-related contribution to its development. In addition, (3) a two-stage hypothesis of pathogenesis of delayed cerebral vasospasm is presented developed in the Vascular Laboratory of Surgical Neurology Branch of the National Institute of Neurological Disorders and Stroke using a primate model of SAH. According to this hypothesis, initially (Phase I) NO-releasing neurons are destroyed by oxyhemoglobin (oxyHb) leading to diminished availability of NO in the vessel wall and constriction of the vessels (Phase I). Increased shear stress evoked by narrowing of the arterial lumen should stimulate endothelial nitric oxide synthase (eNOS). But further metabolism of hemoglobin to bilirubin oxidized fragments (BOXes) increases asymmetric dimethylarginine (ADMA), an endogenous inhibitor of eNOS, in the vicinity of the artery further decreasing of NO availability and sustaining vasospasm (Phase II). In Phase III, the resolution of vasospasm, elimination of BOXes increases NO production by eNOS resulting in recovery of dilatory activity of endothelium. This hypothesis suggests that the key treatment to prevent delayed cerebral vasospasm should be focused on preventing oxyHb neurotoxicity, inhibiting BOX production, and exogenous NO delivery.     

Pathological opening of the blood-brain barrier to horseradish peroxidase and amyloid precursor protein following ischemia-reperfusion brain injury

This study was performed to test the hypothesis that fragments of amyloid precursor protein are able to enter the injured blood-brain barrier (BBB) following brain ischemia. We observed chronic disruption of the BBB after ischemia. The BBB changes did not increase in intensity and frequency with longer periods of recirculation. As an effect of BBB injury, we noted a visible connection of diffuse amyloid plaques with neurovasculature in rats. This pathology appears to have a similar distribution as in Alzheimer's disease, hippocampal and cortical changes being most severe.     

Electrocardiographic signs of anterior myocardial infarction caused by the occlusion of the right ventricular branch of the right coronary artery--a case report

Elektrocardiographic signs of anterior myocardial infarction caused by the occlusion of the right ventricular branch. A case of a 72-year-old male with electrocardiographic symptoms of anterior myocardial infarction resulting from the right ventricular branch occlusion is presented. The mechanisms of eliscrepancy between angiographic and electrocardiographic findings are discussed and diagnostic as well as therapeutic procedures are described.     

Influence of hydrophiling agents on gel formation rate on Carbopol base

The aim of the study was to assess the impact of substrate composition on the physicochemical and pharmaceutical availability of hydrocortisone. Gels prepared on the basis of contained varying amounts of Carbopol propylene glycol-1,2, and polyethylene glycol 200. Applied hydrophilic substances affect the diversity of hydrocortisone half release times from hydrogels.     

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

AIM

To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis).

METHODS

All subjects received a single transdermal 10 cm² patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h⁻¹). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites.

RESULTS

Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,t_last) and C_max for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for C_max for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency.

CONCLUSIONS

The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis.