Hydrophilic and cationic latex particles for the specific extraction of nucleic acids

The adsorption of BSA and RNA onto hydrophilic and thermosensitive poly(N-isopropyl-acrylamide) (NIPAM) latex particles was described as a function of pH, ionic strength and temperature. The hydrogel poly(NIPAM) latex was synthesized by precipitation polymerization in the presence of a cationic amino-containing monomer. The latex obtained was characterized in terms of particle size, and electrophoretic mobility as a function of pertinent variables: pH, temperature and ionic strength. The adsorption of BSA onto the latex was investigated to identify the conditions at which the adsorbed amount of BSA was negligible. The adsorption of RNA was studied to establish the conditions which give rise to maximal adsorption of RNA. In order to favor the desorption of RNA, desorption was investigated by changing the pH, ionic strength, and temperature. The adsorption of BSA was found to be lower at 20 than at 40 degrees C. However, the adsorption of RNA is drastically affected by the pH and the ionic strength of the medium. Maximal adsorbed amounts were obtained at acidic pH, 20 degrees C, and low ionic strength. The adsorption is shown to decrease when the pH, temperature and ionic strength increase, implying that the adsorption was mainly governed by electrostatic interactions. Maximal release of RNA molecules was obtained at high ionic strength and basic pH.     

Malaria transmission in an area of future vaccination in equatorial forest of south Cameroon

In order to describe malaria transmission in a future antigamete vaccine trial area, a longitudinal entomological study was conducted, together with parasitological and immunological surveys, from June 1997 to May 1998 in two nearby villages in a tropical rain forest area 100 km east of Yaoundé. Koundou is located along the main road in an open and degraded environment combining cultivated lands and forests; Ebolakounou is located 5 km from the road in forest surroundings. Indoor mosquito night catches no human volunteers were performed twice a month, in ten houses. We determined the entomological infection rate as 176 infected bites per human per year in Koundou (47.7% for An. moucheti, 47.3% for An. gambiae and 5% for An. funestus) and only 17.7 infected bites/human/year in Ebolakounou, with An. gambiae only. Transmission appears to be ten times higher in the village situated in a degraded environment than in the village situated in the rainforest.     

An in vivo model of femtosecond laser intrastromal refractive surgery

BACKGROUND AND OBJECTIVE: To develop an animal model for evaluation of femtosecond laser intrastromal refractive surgery. METHODS: Intrastromal photodisruption was performed in New Zealand Albino rabbits using a femtosecond laser system. This surgical pattern consisted of a 100 microm-tick pyramid of laser pulses starting 180 microm below the corneal surface. Animals underwent serial slit lamp examinations and corneal thickness measurements at 1,3,7,14, and 28 days, then monthly up to 1 year. RESULTS: Approximately 70 microm of central corneal thinning were seen at 1 week, remaining stable up to 7 months. CONCLUSIONS: Intrastromal photodisruption with femtosecond lasers produced consistent changes in corneal thickness without loss of corneal transparency. These changes were more stable than those produced with excimer laser procedures in a similar animal model.     

Atypical antipsychotic-induced neutropenia in dogs

DMP 406 is an atypical antipsychotic, antischizophrenic drug, biochemically related to clozapine, which exerts its desired pharmacologic effects through selective antagonism of 5-hydroxytryptamine and dopamine-receptor subtypes. Clozapine therapy is clinically associated with severe granulocytopenia in a small subset of patients. In the course of a 3-month toxicity study in dogs, severe neutropenia, thrombocytopenia, marked myeloid and erythroid left-shifted bone marrow hyperplasia with increased erythrophagocytosis, positive Coombs' tests, and hypergammaglobulinemia occurred in individual females dosed with 30 mg/kg/day of DMP 406. Related but less severe changes were also observed in males. Sera or purified immunoglobulins from affected and control dogs were tested in methylcellulose-based, canine hematopoietic colony-forming unit (CFU) assays with or without DMP 406. Neither size nor number of erythroid or myeloid CFUs differed between cultures containing control or affected dog serum components. Sera from individual affected dogs but not controls resulted in moderate numbers of fibroblast-like CFUs, suggesting DMP 406-associated marrow stromal cell-modifying, serum activities to be present. DMP 406 alone resulted in a concentration-dependent reduction of erythroid and myeloid CFUs with an approximate IC50 of 3.0 microg/mL. Taken together, DMP 406-induced granulocytopenia and bone marrow dyscrasia appear likely to result from both immune-mediated and direct drug-induced myelotoxicity.     

Current clinical issues on mycoses in neutropenic patients

Invasive fungal infections, which are associated with high morbidity and mortality rates, are an increasing challenge for the management of immunocompromised hosts, particularly neutropenic cancer patients. Due to the ageing population, recent progress in cancer therapy and better prognosis of bacterial infections, the numbers of patients at risk of life-threatening mycoses are increasing. The percentage of cancer patients with evidence of an invasive fungal infection ranges from approximately 5% to 30%. The most common opportunistic fungal pathogens are Candida spp. and Aspergillus spp. but recently unusual pathogens including Fusarium, Trichosporon and many others have been increasingly reported. Although some progress has been made in the last decade, several controversial issues need to be addressed by clinicians as well as by medical microbiologists and mycologists involved in the care of patients experiencing fungal infections. A comprehensive clinical strategy, such as that initiated under the auspices of EORTC is a meaningful approach to ensure high quality clinical research in that field in order to define guidelines for more effective diagnosis, prevention and treatment approaches of invasive fungal infections in cancer patients at the European level.     

Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA

The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido or an ether function), the position of amino group between the two parts of hybrid molecules, the number of intercalator moieties (ellipticinium) covalently attached to the metalloporphyrin, and the nature of the central metal atom (Mn, Fe, Zn) on the biological activity of these hybrid molecules were studied. In addition, these molecules have a high affinity for double-stranded DNA (affinity constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x 10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210 in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the nature of central atom. Iron derivatives are less active than manganese analogues and the corresponding zinc derivatives are nearly inactive despite their same affinity for nucleic acids. These highly water-soluble hybrid molecules could be considered as efficient bleomycin models based on a cationic metalloporphyrin.     

Effects of tianeptine on spontaneous alternation, simple and concurrent spatial discrimination learning and on alcohol-induced alternation deficits in mice

The effects of systemic administration of tianeptine, a new psychotropic agent with antidepressant properties, were investigated on spontaneous alternation behavior, and on simple and concurrent spatial discrimination, in normal mice of the BALB/c strain. Tianeptine increased rates of spontaneous T-maze alternation, facilitated retention of a T-maze left-right discrimination, and speeded up acquisition of concurrent discrimination in a radial maze. These effects were consistent across successive experiments with a dose of 10mg/kg; lower doses (2.5 and 5.0mg/kg) had less or no effect depending on the task. These results, together with theoretical considerations, led us to investigate the effect of tianeptine on the sequential-specific alternation deficit induced by long-term ethanol administration in the same strain of mice. Results showed that, at the dose of 10mg/kg, the drug completely alleviated the alcohol-induced deficit. Unlike tianeptine, fluoxetine impaired discrimination performance in the radial maze. These data are discussed in light of the effects of tianeptine on serotonergic transmission and of the role of serotonin and acetylcholine in learning and memory processes.     

Malleolar fractures. Predictive factors for secondary osteoarthritis. Retrospective study of 32 cases

The authors report a series of 32 ankle fractures treated by internal fixation and reviewed with a follow-up of more than 15 years. The series includes 12 fibular, 14 bimalleolar and 6 trimalleolar fractures. Following Weber's classification, there were 4 type A, 18 type B and 10 type C fractures. The postoperative x-ray showed 28 anatomy reductions; shortening of the fibula from 3 to 5 mm was noted in 4 cases. Clinical results were evaluated according to Kitaoka's criteria, and radiological results according to Magnusson's criteria. Statistical analysis was made with a Chi-square test. The retrospective review at an average follow-up of 15 years showed 19 painfree ankles, normal mobility in 22 cases, absence of edema in 18. The shoe-wear was normal in 30 cases. Walking had returned to normal in 23 cases but radiography showed narrowing of the tibiotalar joint line in 12 cases and lengthening of the medial malleolus in 16. Narrowing of the tibiotalar joint space was associated with lengthening of the medial malleolus in 10 cases. The objective results were rated as follows: 23 good, 8 fair, and 1 poor. With a follow-up of 15 years, we noted degenerative changes in the ankle in 37% of cases in spite of an anatomic reconstruction which had been perfect in 28. Shortening of the fibula, observed in 4 cases, was associated with subsequent ossification below the medial malleolus corresponding to avulsion of the non sutured medial collateral ligament. Nevertheless, degenerative changes of the ankle were clinically well-tolerated. The long term result of internal fixation of malleolar fractures was good. This was achieved only through perfect restoration of the joint anatomy. Contrary to other series, non-operative repair of the medial collateral ligament was associated with long team degenerative changes and reduced mobility of the joint. We therefore now advocate surgical repair of the medial collateral ligament.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.