Effects of drug-polymer dispersions on solubility and <Emphasis Type=Italic>in vitro</Emphasis> diffusion of artemisinin across a polydimethylsiloxane membrane

Artemisinin(ART) is a sesquiterpene lactone with an endo-peroxide bridge that is thought to be responsible for its antimalarial activity.It has low oral bioavailability because of aqueous insolubility,which leads to local toxicity at the site of aggregation.The present work focused on increasing its solubility and evaluating its permeation across a model membrane to mimic transdermal delivery that bypasses the hepatic metabolism.For this purpose,physical mixtures(PM),solid dispersions(SD) and lyophilized dispersions(LD) with different drug-polymer ratios(1:0.5,1:1,1:2,1:4 and 1:9) were prepared using the hydrophilic polymer polyvinylpyrrolidone(PVP).Drug-polymer dispersions were characterized using X-ray diffraction(XRD) and Fourier transform infrared spectroscopy(FTIR).Solubility was measured in three solvents:de-ionized water,phosphate buffered saline(PBS) and methanol.The toluene-water partition coefficient was evaluated and compared with the literature and calculated logP values.In vitro diffusion of ART was studied across a polydimethylsiloxane membrane from a saturated solution of drug-polymer dispersions.XRD patterns showed a gradual decrease in crystallinity of ART with increasing polymer concentration,while FTIR confirmed no interactions between ART and PVP.Solubility was increased up to 4-,5-and 8-fold for LD in water,PBS and methanol,respectively.The logP for toluene-water was 2.65 ± 0.3,which is in good agreement with literature and calculated logP values.Permeation was enhanced,which is attributed to the decrease in crystallinity and increase in wettability of the drug.The ART flux was significantly higher than that of pure ART(0.12 ± 0.01) with increasing PVP concentration for SD and LD formulations.In conclusion,drug-polymer dispersions with PVP improve the pharmaceutical properties of ART in the order LD>SD>PM.     

Analysis of structural features responsible for the sweetness of the sesquiterpene,hernandulcin

Summary The relationship between sweetness and structure was studied for several analogues of the intensely sweet sesquiterpene, hernandulcin. These derivatives were prepared synthetically, and were subjected to spectroscopic and conformational analysis. With the exception of the parent substance, none of the derivatives tested proved to be sweet. Evidence gathered in this study suggests that hernandulcin binds to its putative receptor through a three-point interaction, involving the C-1 carbonyl and C-1 hydroxyl groups, and the double bond between C-4 and C-5. In the course of a preliminary safety assessment, the 3-desmethyl derivative of hernandulcin was found to be mutagenic towardSalmonella typhimurium strain TM677.Acknowledgments. We thank Drs A. J. Hopfinger and R. Pearlstein for helpful suggestions concerning the use of CHEMLAB software, and Mr E. F. Robbins of the Research Resources Center, University of Illinois at Chicago for helpful assistance with the MS determinations. During the course of this investigation, one of us (C.M.C.) was affiliated with the Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, and the gratefully acknowledges the support and encouragement of the late Professor Martin P. Schulman. J. M. P. is the recipient of a Research Career Development Award from the National Cancer Institute (1984–1989).Paper 14 in the series Potential Sweetening Agents of Plant Origin. For paper 13, see Nanayakkara, N. P. D., Hussain, R. A., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., J. med. Chem., in press.     

Effect of cement types, mineral admixtures, and bottom ash on the curing sensitivity of concrete

The curing sensitivity of concrete with cement Types 1, 3, and 5 as well as multiple powders consisting of cement, fly ash, and limestone powder was studied. Bottom ash was also used in the study as an internal curing agent and a partial substitution of fine aggregate. The curing sensitivity index was calculated by considering the performances of compressive strength and carbonation depth. Specimens were subjected to two curing conditions: continuously water-cured and continuously air-cured. The results show that cement Type 3 has a lower curing sensitivity, while cement Type 5 increases the curing sensitivity. For the mixes without bottom ash, the use of fly ash increases the curing sensitivity, while limestone powder reduces the curing sensitivity of concrete. The use of bottom ash in concrete reduces the curing sensitivity, especially at a lower mass ratio of water to binder. Concrete with limestone powder, together with bottom ash, is least sensitive to curing. The curing sensitivity calculated from carbonation depth also has a similar tendency as that derived by considering compressive strength. From the test results of compressive strength and curing sensitivity, bottom ash has been proven to be an effective internal curing agent.     

The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J

The protein predicted to be defective in individuals with Fanconi anemia complementation group J (FA-J), FANCJ, is a missing component in the Fanconi anemia pathway of genome maintenance. Here we identify pathogenic mutations in eight individuals with FA-J in the gene encoding the DEAH-box DNA helicase BRIP1, also called FANCJ. This finding is compelling evidence that the Fanconi anemia pathway functions through a direct physical interaction with DNA.     

Vestibular evidence for the evolution of aquatic behaviour in early cetaceans

Early cetaceans evolved from terrestrial quadrupeds to obligate swimmers, a change that is traditionally studied by functional analysis of the postcranial skeleton. Here we assess the evolution of cetacean locomotor behaviour from an independent perspective by looking at the semicircular canal system, one of the main sense organs involved in neural control of locomotion. Extant cetaceans are found to be unique in that their canal arc size, corrected for body mass, is approximately three times smaller than in other mammals. This reduces the sensitivity of the canal system, most plausibly to match the fast body rotations that characterize cetacean behaviour. Eocene fossils show that the new sensory regime, incompatible with terrestrial competence, developed quickly and early in cetacean evolution, as soon as the taxa are associated with marine environments. Dedicated agile swimming of cetaceans thus appeared to have originated as a rapid and fundamental shift in locomotion rather than as the gradual transition suggested by postcranial evidence. We hypothesize that the unparalleled modification of the semicircular canal system represented a key 'point of no return' event in early cetacean evolution, leading to full independence from life on land.     

Autofluorescence of isolated unfixed rabbit deiters' neurons and surrounding neuroglial clumps

Résumé Nous avons démontré l'autofluorescence dans des neurones et neuroglies détachées du noyau de Deiters du lapin. Les cellules furent isolées et examinées dans une solution de 0.9% NaCl, sans fixation, deshydration ou addition de fluorochromes. La longueur d'onde de la fluorescence était 5400–5700 Å, et la fluorescence apparaissait d'habitude dans le cytoplasme et le nucléode. On a conclu qu'elle provient de la lipofuscine.     

Eocene evolution of whale hearing

The origin of whales (order Cetacea) is one of the best-documented examples of macroevolutionary change in vertebrates. As the earliest whales became obligately marine, all of their organ systems adapted to the new environment. The fossil record indicates that this evolutionary transition took less than 15 million years, and that different organ systems followed different evolutionary trajectories. Here we document the evolutionary changes that took place in the sound transmission mechanism of the outer and middle ear in early whales. Sound transmission mechanisms change early on in whale evolution and pass through a stage (in pakicetids) in which hearing in both air and water is unsophisticated. This intermediate stage is soon abandoned and is replaced (in remingtonocetids and protocetids) by a sound transmission mechanism similar to that in modern toothed whales. The mechanism of these fossil whales lacks sophistication, and still retains some of the key elements that land mammals use to hear airborne sound.     

Fertilizer residue from labelled urea in a clay soil

Summary The proportion of nitrogen obtained by wheat Pak-70 from N¹⁵ labelled urea applied at the rate of 120 kg N/ha was less than 35%. Leaching of nitrogen beyond the root zone was shown to be negligible. Most of the nitrogen was therefore left in the soil as residue. The increase in soil inorganic nitrogen values after the wheat harvest confirmed the presence of residual nitrogen.Acknowledgment. This work was sponsored jointly by the International Atomic Energy Agency and the Pakistan Atomic Energy Commission under Research Contract No. 1673/GS. The authors are grateful to the IAEA for providing some essential equipment and analyses of wheat samples for N¹⁵.     

Effect of oxygen content on the structural and optical properties of ZnO films grown by atmospheric pressure MOCVD

Atmospheric pressure MOCVD was used to deposit ZnO layers on sapphire and homoepitaxial template under different oxygen flow rates.Oxygen content affects the lattice constant value and texture coefficient of the films as evidenced by the θ-2θ peaks position and their intensity.Films deposited at lower oxygen flow rate possess higher value of strain and stresses.ZnO films deposited at high oxygen flow rates show intense UV emissions while samples prepared under oxygen deficient conditions exhibited defect related emission along with UV luminescence.The results are compared to the ZnO films deposited homoepitaxially on annealed ZnO samples.The data obtained suggest that ZnO stoichiometry is responsible for the structural and optical quality of ZnO films.