Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia

Cannabinoids have neuroprotective potentials, and the expression of endocannabinoids as well as cannabinoid receptors is induced after cerebral ischemia. They also induce hypothermia by lowering the hypothalamic set point. We have estimated the significance of such hypothermia in ischemic neuroprotection following systemic administration of WIN 55,212-2, a synthetic cannabinoid receptor agonist. Results showed that WIN 55,212-2 significantly reduced infarct volumes of rats subjected to focal cerebral ischemia (middle cerebral artery occlusion) and significantly decreased ischemic CA1 damage in rats subjected to global cerebral ischemia (two-vessel occlusion). A significant (approximately 50%) part of this neuroprotection was provided by WIN 55,212-2 induced hypothermia (33.7+/-1.1 degrees C/34.9+/-1.6 degrees C), because prevention of hypothermia by maintaining body core temperatures between 37.0 and 38.0 degrees C dissolved the neuroprotective effect into a hypothermic component and an unidentified component. Finally, the ability of WIN 55,212-2 to reduce levels of the proinflammatory cytokine IFNgamma in the infarcted hemisphere of rats subjected to focal cerebral ischemia required hypothermia. For the cannabinoid WIN 55,212-2, we have isolated and directly demonstrated that hypothermia is only part of, although significant, cannabinoid mediated neuroprotection in both global and focal cerebral ischemia. We conclude that cannabinoids are reliable candidates for drug-induced hypothermia and neuroprotection. These neuroprotective effects of cannabinoids could provide the basis for potential therapeutic uses of cannabinoids and/or endocannabinoids in stroke.     

Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study.

OBJECTIVE--To find out whether a 10-14 days'' course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics. DESIGN--Prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics. Patients were seen at three and six weeks and three, six, nine, 12, and 18 months after their first visit. SETTING--Departments of infectious diseases in three hospitals in Linköping, Malmö, and Stockholm, Sweden. PATIENTS--40 Consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks. INTERVENTIONS--20 Patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics. All patients received non-steroidal anti-inflammatory drugs, and four also received intra-articular steroid injections after at least six weeks'' observation. MAIN OUTCOME MEASURES--Arthritic symptoms assessed clinically and by using Ritchies'' index; blood measurements reflecting inflammatory activity; serum IgG, IgM, and IgA antibody titres; HLA tissue type. RESULTS--No difference was observed concerning duration of arthritis, grade of inflammation, and number of joints affected between patients treated and those not treated with antibiotics. Furthermore, there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin, IgG, and IgA concentrations. All values had returned to normal within three months. No patient developed chronic arthritis, but sustained slight arthralgia occurred in three patients. The HLA-B27 antigen was found in 23 (58%) of the patients, and its presence did not affect clinical outcome. The IgG, IgM, and IgA antibody responses were similar in patients treated with antibiotics and those not treated. CONCLUSION--Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection.     

The flower and the butterfly constructed wetland system at Koh Phi Phi—System design and lessons learned during implementation and operation

In 2007, a constructed wetland system was implemented on the tourist island of Koh Phi Phi in Southern Thailand. This paper presents the process of planning, designing and implementing the system and discusses the performance and operational issues 3 years after implementation. The system is an international lighthouse project showing the potential for aesthetical integration of constructed wetland systems in the built environment. The system comprises a wastewater collection system for the main business and hotel area of the island, a pumping station and a pressure pipe system to the treatment facility, a multi-stage constructed wetland system, and a system for reuse of treated wastewater. The treatment chains consist of vertical-flow, horizontal subsurface flow and free water surface flow units. Because the treatment system is located at the centre of the island, surrounded by resorts, restaurants and shops, the systems are designed with terrains as scenic landscaping. The wastewater is treated to meet the Thai effluent standards for total suspended solids and nitrogen, but because of inadequate pre-treatment and removal of oil and grease prior to the system, the standards for oil and grease and BOD are not met. A number of challenges during construction and operation have caused problems with clogging of the vertical flow constructed wetlands and given rise to odour problems. Safeguards were prepared, but not effectively activated, mainly because no key-person or key-authority took responsibility for managing the system.     

Proposed function of the accumulation of plasma membrane-type Ca2+-ATPase mRNA in resting cysts of the ciliate Sterkiella histriomuscorum

From an mRNA differential-display analysis of the encystment-excystment cycle of the ciliate Sterkiella histriomuscorum, we have isolated an expressed sequence tag encoding a plasma membrane-type Ca2+-ATPase (PMCA). PMCAs are located either in the plasma membranes or in the membranes of intracellular organelles, and their function is to pump calcium either out of the cell or into the intracellular calcium stores, respectively. The S. histriomuscorum macronuclear PMCA gene (ShPMCA) and its corresponding cDNA were cloned; it is the first member of the Ca2+-ATPase family identified in Sterkiella. The predicted protein of 1,065 amino acids exhibits 37% identity with PMCAs of diverse organisms. A phylogenetic analysis showed its relatedness to homologs of two alveolates: the ciliate Paramecium tetraurelia and the apicomplexan Toxoplasma gondii. Overexpression of the protein ShPMCA failed to rescue the wild-type phenotype of three Ca2+-ATPase-defective mutant strains of Saccharomyces cerevisiae; this failure contrasts with the reported ability of the PMCAs of parasites to complement defects in yeast. ShPMCA mRNA is markedly accumulated during encystment and in resting cysts, suggesting a function during excystment. To address the possibility of a signaling role for calcium at excystment, the capacity of calcium to induce excystment was examined.     

A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption

Microtubule disruption by colchicine induces apoptosis in selected neuronal populations. However, little is known about the upstream death signalling events mediating the neurotoxicity. We investigated first whether colchicine-induced granule cell apoptosis activates the c-Jun N-terminal kinase (JNK) pathway. Cultured murine cerebellar granule cells were exposed to 1 microm colchicine for 24 h. Activation of the JNK pathway was detected by western blotting as well as immunocytochemistry using antibodies against phospho-c-Jun (p-c-Jun). Next, adult male rats were injected intracerebroventricularly with colchicine (10 microg), and JNK pathway activation in dentate granule cells (DGCs) was detected by antibodies against p-c-Jun. The second part of the study tested the involvement of mixed lineage kinases (MLK) as upstream activators of the JNK pathway in colchicine toxicity, using CEP-1347, a potent MLK inhibitor. In vitro, significant inhibition of the JNK pathway, activated by colchicine, was achieved by 100-300 nm CEP-1347, which blocked both activation of cell death proteases and apoptosis. Moreover, CEP-1347 markedly delayed neurite fragmentation and cell degeneration. In vivo, CEP-1347 (1 mg/kg) significantly prevented p-c-jun increase following injection of colchicine, and enhanced survival of DGCs. We conclude that colchicine-induced neuronal apoptosis involves the JNK/MLK pathway, and that protection of granule cells can be achieved by MLK inhibition.     

Development, growth and egg production of the two copepod species Centropages hamatus and Centropages typicus in the laboratory

Laboratory experiments were set up in order to determine andcompare developmental rates, growth rates, generation timesand egg production rates for the two calanoid copepod speciesCentropages typicus and Centropages hamatus. The nauplii showeda higher developmental rate than the copepodites for both specieswith quite different individual stage durations, which gaveno indication of isochronal development. For C typicus equiproportionaldevelopment was found. The growth rates were exponential andhighest for the largest species C typicus, and for both speciesthe juvenile growth rates were very similar to the egg productionrates of the adults.