Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard

Drug abuse robs individuals of their jobs, their families, and their free will as they succumb to addiction; but may cost even more: a life of disability or even life lost due to stroke. Many illicit drugs have been linked to major cardiovascular events and other comorbidities, including cocaine, amphetamines, ecstasy, heroin, phencyclidine, lysergic acid diethylamide, and marijuana. This review focuses on available epidemiological data, mechanisms of action, particularly those leading to cerebrovascular events, and it is based on papers published in English in PubMed during 1950 through February 2011. Each drug's unique interactions with the brain and vasculature predispose even young, healthy people to ischemic or hemorrhagic stroke. Cocaine and amphetamines have the strongest association with stroke. However, the level of evidence firmly linking other drugs to stroke pathogenesis is weak. Large epidemiological studies and systematic evaluation of each drug's action on the brain and cardiovascular system are needed to reveal the full impact of drug use on the population

Sperm collection and storage for the sustainable management of amphibian biodiversity

Current rates of biodiversity loss pose an unprecedented challenge to the conservation community, particularly with amphibians and freshwater fish as the most threatened vertebrates. An increasing number of environmental challenges, including habitat loss, pathogens, and global warming, demand a global response toward the sustainable management of ecosystems and their biodiversity. Conservation Breeding Programs (CBPs) are needed for the sustainable management of amphibian species threatened with extinction. CBPs support species survival while increasing public awareness and political influence. Current CBPs only cater for 10% of the almost 500 amphibian species in need. However, the use of sperm storage to increase efficiency and reliability, along with an increased number of CBPs, offer the potential to significantly reduce species loss. The establishment and refinement of techniques over the last two decades, for the collection and storage of amphibian spermatozoa, gives confidence for their use in CBPs and other biotechnical applications. Cryopreserved spermatozoa has produced breeding pairs of frogs and salamanders and the stage is set for Lifecycle Proof of Concept Programs that use cryopreserved sperm in CBPs along with repopulation, supplementation, and translocation programs. The application of cryopreserved sperm in CBPs, is complimentary to but separate from archival gene banking and general cell and tissue storage. However, where appropriate amphibian sperm banking should be integrated into other global biobanking projects, especially those for fish, and those that include the use of cryopreserved material for genomics and other research. Research over a broader range of amphibian species, and more uniformity in experimental methodology, is needed to inform both theory and application. Genomics is revolutionising our understanding of biological processes and increasingly guiding species conservation through the identification of evolutionary significant units as the conservation focus, and through revealing the intimate relationship between evolutionary history and sperm physiology that ultimately affects the amenability of sperm to refrigerated or frozen storage. In the present review we provide a nascent phylogenetic framework for integration with other research lines to further the potential of amphibian sperm banking

Fibrinolytic therapy for thrombosis in cardiac valvular prosthesis short and long term results

OBJECTIVE: To assess the short- and long-term results of the use of streptokinase (SK) for the treatment of thromboses in cardiac valvular prostheses. METHODS: Seventeen patients with cardiac prosthetic thrombosis diagnosed by clinical, echocardiographic, and radioscopic findings underwent fibrinolytic treatment with a streptokinase bolus of 250,000 U followed by 100.000 U/hour. Short- and long-term results were assessed by radioscopy and echocardiography. RESULTS: Of the 17 patients, 12 had mechanical double-disk prostheses (4 aortic, 6 mitral, 2 tricuspid), 4 had single-disk prostheses (2 aortic, 1 mitral, and 1 tricuspid), and 1 had a tricuspid bioprosthesis. The success rate was 64.8%, the partial success rate was 17.6%, and the nonsuccess rate was 17.6%. All patients with a double-disk prosthesis responded, completely or partially, to the treatment. None of the patients with a single-disk prosthesis had complete resolution of the thrombosis. The time of streptokinase infusion ranged from 6 to 80 hours (mean of 56 h). The mortality rate due to the use of streptokinase was 5.8% and was secondary to cerebral bleeding. During streptokinase infusion, 3 (17.6%) embolic episodes occurred as follows: 1 cerebral, 1 peripheral, and 1 coronary. The rethrombosis index was 33% in a mean follow-up of 42 months. CONCLUSION: The use of fibrinolytic agents was effective and relatively safe in patients with primary thrombosis of a double-disk prosthesis. A fatal hemorrhagic complication occurred in 1 (5.8%) patient, and embolic complications occurred in 3 (17.6%) patients. In a mean 42-month follow-up, 67% of the patients were free from rethrombosis

Resonant ionization of shallow donors in electric field

In this paper, we report on our experimental observations of the resonant ionization of a phosphorus donor in silicon in a homogeneous electric field, which is expressed in the sudden rise of the conductivity of the sample at a low temperature when the electric field approaches the critical value of ∼3.2 MV m-1. The effect is discussed in terms of the field-induced interaction of the states using a simplified model based on the effective-mass theory. The results from our model are qualitatively similar to the previously published advanced model base, which is based on the first principles; this predicts the ionization thresholds at approximate fields of 2.45 and 3.25 MV m-1, the latter being in very good agreement with our experiment. The possibility of observing more than one resonance is also discussed

Ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5a,8a-epidioxycholest-6-en-3β-isolated from the mollusk dolabrifera dolabrifera shows significant activity against leishmania donovani

An ecology- and bioassay-guided search employed to discover compounds with activity against tropical parasitic diseases and cancer from the opisthobranch mollusk, Dolabrifera dolabrifera, led to the discovery of antileishmanial properties in the known compound, 5a,8a-epidioxycholest-6- en-3ß-ol (1). Compound 1 was identified through nuclear magnetic resonance spectroscopy (1H, 13C) and mass spectrometry. The compound was concentrated in the digestive gland of D. dolabrifera, but was not detected in other body parts, fecal matter or mucus. Compound 1 showed an IC50 of 4.9 μM towards the amastigote form of Leishmania donovani compared with an IC50 of 281 μM towards the control Vero cell line, a 57.3-fold difference, and demonstrated no measurable activity against Plasmodium falciparum, Trypanosoma cruzi, and the breast cancer cell line, MCF-7

Sequestration and cyanobacterial diet preferences in the opisthobranch molluscs Dolabrifera nicaraguana and Stylocheilus rickettsi

A multidisciplinary approach was used to assess chemical ecological dietary interactions between marine organisms as a tool to isolate novel ecologically relevant compounds with biotechnological potential. First, laboratory-based feeding preference assays of the sea hare Dolabrifera nicaraguana (previously known as D. dolabrifera), an anaspidean mollusc, were conducted by simultaneously offering six food options collected from nearby tidal pools in the Coiba National Park in the Tropical Eastern Pacific of Panama. An evaluation of preferred dietary repertoire revealed D. nicaraguana significantly preferred cf. Lyngbya sp. over the cyanobacterium Symploca sp., green alga Chaetomorpha sp., and red alga Spyridia sp. A no-choice feeding assay using cf. Lyngbya sp. or green alga Cladophora sp. supported this finding. Secondly, we conducted bioactivity-guided fractionation using the preferred food source of D. nicaraguana, the ‘hair-like” cf. Lyngbya sp. from which we also isolated and elucidated two new depsipeptide compounds, veraguamide M (1) and veraguamide N (2). Veraguamides M (1) and N (2) showed in vitro activity toward the malaria-causing parasite Plasmodium falciparum with GI50 values of 4.2 and 4.3 mM, respectively, and therapeutic windows of 7.0–8.0 (based on moderate cytotoxicities to mammalian Vero cells with GI50 values of 29.3 and 34.1 mM, respectively). Veraguamide N (2) was also active against Leishmania donovani, the causative agent of visceral leishmaniasis, with a GI50 value of 6.9 mM. We then evaluated sequestration of these new compounds by D. nicaraguana used in the feeding assays and found trace amounts of the dietary sequestered compounds. Finally, we evaluated sequestration of these new compounds by the sea hare Stylocheilus rickettsi (previously known as S. striatus) that were grazing on the cf. Lyngbya sp. used in the feeding assays and found both to be sequestered. This study is the first example whereby compounds with significant activity against tropical parasites have been found in both the sea hare S. rickettsi and its cyanobacterial food source. These results suggest that chemical ecological studies involving sea hares and cyanobacteria continue to provide a diverse source of bioactive compounds with biotechnological potential