Conformal proton therapy for prostate carcinoma

The suppression of apoptosis may contribute to the carcinogenicity of the peroxisome proliferators (PPs), a class of non-genotoxic rodent hepatocarcinogens. Our previous work demonstrated that the PP nafenopin suppressed both spontaneous and transforming growth factor beta1 (TGFbeta1)-induced hepatocyte apoptosis both in vivo and in vitro. Here, we extend these observations by demonstrating the ability of nafenopin to suppress apoptosis induced by other major candidates for the signalling of cell death in the liver. Treatment of rat or mouse hepatocyte monolayers with TGFbeta1 or the DNA damaging drugs etoposide or hydroxyurea induced high levels of apoptosis. Western blot analysis did not support a role for either p53 or p21waf1 in etoposide-induced apoptosis in rat hepatocytes. Treatment of mouse hepatocytes with an agonistic anti-Fas antibody also resulted in an induction of high levels of apoptosis. Pre-addition and continued exposure to nafenopin suppressed apoptosis induced by all three stimuli. Overall, our studies demonstrate that the ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus. It is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways. However, it seems more likely that nafenopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism.     

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.     

Comparative evaluation of surfactant and hydrophobizing agent concentration in relation to the optimal particle size of metered-dose inhalers

The aim of the present study was to formulate stabilized suspension-type metered-dose inhalation aerosols, and to examine the connection between the stabilizing additives and the optimal particle size. For the stabilization of the suspended particles, hydrophilic- and hydrophobic-type additives were applied. Oleil oleate was selected as a hydrophilic anionic surfactant, and the hydrophobizing agent was dimethyl siloxane polymer. The effect of the amount of the applied hydrophilic and hydrophobic additives on the optimal particle size was modeled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design. We found that if the proper type and amount of additives are selected, it is possible to acquire the therapeutically best composition.     

Interface potential of calcium phosphate in simulated body fluid

Calcium phosphate ceramics are used in the substitution of injured or damaged bones. Nevertheless, the behaviour of these materials, and in particular, the mechanisms guiding their interface response in physiological environment is still unknown. This work describes the construction of hydroxyapatite and tricalcium phosphate electrodes used to determine the interface potential behaviour of these materials in a simulated body fluid, in a pH range corresponding to the variation observed in human body injuries, at ambient and physiological temperatures. These measurements are associated with the adsorption/desorption of ions from the materials. The results show that hydroxyapatite and tricalcium phosphate have similar behaviour in that they reach an interface potential equilibrium state faster when the solution pH is decreased and the temperature increased. This behaviour may be attributed to their ability to form a calcium-rich layer and is relevant to their quality as implantable materials.     

Differential assembly kinetics of alpha-tubulin isoforms in the presence of paclitaxel

The ability of six rapid DNA extraction procedures to provide DNA for the polymerase chain reaction from archival Giemsa-stained bone marrow slides was tested on 120 samples. Boiling in distilled water, freeze-thaw method, boiling in 10% Chelex-100 resin solution, proteinase K/Tween 20/NP-40 method coupled with simplified phenol/ chloroform/isoamyl alcohol protocol or salting-out procedure using saturated NaCl and modification of commercial QIAamp procedure (Qiagen. Chatsworth, Calif.) gave DNA extraction efficiencies of 50%, 70%, 85%, 95%, 100% and 100%, respectively. Our results demonstrate that rough DNA extraction methods have decreased efficiencies compared to complete DNA extraction protocols and that the latter are required to ensure highly reproducible results from archival Giemsa-stained bone marrow slides.     

EFficacy of albendazole for treatment of naturally acquired fasciola hepatica in calves

In calves given various doses of albendazole as a 4.55% (w/v) drench suspension, removal efficacies against mature Fasciola hepatica were 77.5% with the dose of 7.5 mg/kg; 92.3%, with 10 mg/kg; and 85.9%, with 15 mg/kg. Against immature F hepatica, drug efficacies with these doses were 32.7%, 20.0%, and 36.7%, respectively. Reductions in length and width measurements of mature and immature flukes recovered from the bile ducts correlated with the larger doses reflected a greater efficacy against mature flukes or a possible inhibiting effect of the drug on fluke size or growth. Numbers of eggs recovered in bile at necropsy were reduced by 87.8% with the dose of 7.5 mg/kg; 91.8%, with 10 mg/kg; and 95.6%, with 15 mg/kg.     

Expression of de novo high-lysine alpha-helical coiled-coil proteins may significantly increase the accumulated levels of lysine in mature seeds of transgenic tobacco plants

Transgenic insect technology will provide opportunities to explore the basic biology of a broad range of insect species in ways that will prove insightful and important. It is also a technology that will provide opportunities to manipulate the genotypes of insects of practical significance to the health and welfare of humans. The Hermes transposable element from the housefly, Musca domestica, is a short inverted repeat-type element related to hobo from Drosophila melanogaster, Ac from Zea mays, and Tam3 from Antirrhinum majus. It has potential to become a versatile and efficient broad host-range insect transformation vector. The ability of Hermes to transpose when introduced into five species of diptera from four divergent families was tested using an in vivo, interplasmid transpositional recombination assay. Hermes was capable of transposing in all species tested, demonstrating that Hermes has a broad host-range. In addition, the rates of transposition were sufficiently high in all species tested to suggest that Hermes will be an efficient gene transfer vector in a wide range of insect species. The Hermes element also revealed a pattern of integration into the target substrate that permitted factors determining integration site selection to be identified. Primary nucleotide sequence of the integration site played a role as did proximity to preferred integration sites and the nucleosomal organization of the target.     

The relation between induced abortion and ectopic pregnancy

The present study was conducted to elucidate the effects of tirilazad mesylate (U-74006F), a potent inhibitor of lipid peroxidation, on vessel diameter, capillary perfusion, and contractile function of rat cremaster muscle during a 90-minute reperfusion period that followed 4 hours of warm ischemia. Two groups of 32 animals were treated with either 3 mg/kg U-74006F or the vehicle (citrate buffer) alone 30 minutes before ischemia, 90 minutes after ischemia, and immediately before reperfusion. With use of intravital videomicroscopy, the internal luminal diameters of preselected vessels were measured prior to ischemia and during reperfusion. The area that filled with fluorescein was determined at 15-minute intervals for as long as 90 minutes of reperfusion, and contractile function was examined in vitro in an organ bath at that point. In the U-74006F group, after 90 minutes of reperfusion the vessel diameters returned completely to baseline and the diameters of all three categories of vessels at every time point from 10 to 90 minutes of reperfusion had significantly more rapid recovery than the controls. Although some evidence of more rapid fluorescence was noted in the U-74006F group, the two groups did not differ significantly at any time period of reperfusion. In response to tetanic stimulation, the muscles treated with U-74006F had a significantly greater contractile force at all stimulation frequencies than the control muscles. Our findings indicate that pretreatment with U-74006F can effectively decrease the rise of vascular resistance and preserve the contractile function of skeletal muscle during early reperfusion, thereby attenuating ischemia-reperfusion injury.