Thrombolytic therapy for acute ischemic stroke : issues and answers.

Thrombolytic therapies have perhaps been the most important single development in the management of acute ischemic stroke. Results of the National Institute of Neurologic disorders and Stroke (NINDS) trial revealed a 30% greater chance of being disability free at three months if patients with acute ischemic stroke were treated with recombinant tissue plasminogen activator (rt-PA) within 3 hours of onset. These results have been validated in large community studies in the United States. The Prolyse in Acute Cerebral Thromboembolism (PROACT II) trial further demonstrated that patients with middle cerebral artery occlusion can be treated up to 6 hours of onset of stroke with intra-arterial Pro-urokinase. In spite of these results, community use of thrombolytic therapy remains dismally low. Increasing stroke awareness in the community, establishing primary to tertiary stroke centers and physician education are possible methods of increasing utilization of thrombolytic therapy.

Imaging in acute ischemic stroke : relevance to management.

With the advent of thrombolytic therapy in the treatment of acute ischemic stroke, it has become increasingly important to identify the suitable patients for whom such therapy may be useful. The success of reperfusion therapy depends on salvaging ischemic tissue at risk (penumbra). Imaging techniques continue to evolve. MRI with diffusion weighted and perfusion imaging can identify the penumbra (diffusion-perfusion mismatch). MR Angiography provides additional information about large and medium size vessel occlusion. However, MRI is limited by its lesser availability and slower acquisition times. Ultrafast perfusion CT scans are more widely available and seem capable of identifying the ischemic tissue at risk. Newer techniques of perfusion CT and triphasic perfusion CT are becoming more refined and along with CT Angiography provide information not only of the penumbra but also of large vessel occlusion. Patients with large vessel occlusion of the internal carotid and middle cerebral artery are best treated by intra-arterial thrombolytic therapy whereas branch occlusions are suitable for intravenous thrombolysis. Patient selection, based on the present and evolving MRI and CT techniques would provide a more rational application of treatment (greater chances of reperfusion and minimizing the possibility of symptomatic intracerebral hemorrhage).

Liposomal hamycin in the control of experimental aspergillosis in mice: relative toxicity, therapeutic efficacy and tissue distribution of free and liposomal hamycin.

Therapeutic efficacy of liposomal Hamycin has been evaluated in an animal model system for aspergillosis in Balb/c mice. Hamycin was intercalated into soya phosphatidyl choline (SPC), SPC: choline (1:1, vol./vol.) and DMPC liposomes. A single dose of either 0.1 mg/kg, 0.25 mg/kg or 0.5 mg/kg of liposomal Hamycin and 0.1 mg/kg of free Hamycin was injected (i.v.) into animals infected with Aspergillus fumigatus. An increase in the survival rate of animals along with decrease in fungal count in various organs was observed with liposomal administration. Incorporation of cholesterol into liposomes decreased the in vivo toxicity of Hamycin in a dose dependent manner. However, antifungal activity both in the presence and absence of cholesterol showed marked variation as compared to that of non-aromatic polyenes, e.g. amphotericin B. Analysis of Hamycin distribution by HPLC in various tissues revealed higher blood concentration of this drug, when given in free form, compared to its liposomised form. These studies suggest that liposomal Hamycin is more effective than free Hamycin in controlling the experimental Aspergillosis.

Macrophages in host defence--an overview.

The importance of macrophages in host defence is well documented. They are distributed in various tissues where they perform functions in normal steady state as well as in diseased condition. Macrophages secrete a number of enzymes, plasma proteins, complement and coagulation factors which regulate the effector functions of the macrophages. Exposure of macrophages to pathogens results in further metabolic changes which activate the former to secrete oxygen metabolites leading to their augmented microbicidal activity. Macrophages respond to the external stimuli by expressing a large repertoire of surface receptors which play an important role in the activation, recognition and endocytosis of foreign microorganisms. A large number of intracellular pathogens are harboured in the macrophages which can reside and replicate in them. A variety of strategem has been employed to target drugs to vacuolar apparatus of the macrophages in order to combat intracellular pathogens. This review covers some of these aspects particularly in relation to hose defence and methods by which therapeutic agents could be specifically delivered to macrophages.