Antimalarial Properties of Imipramine and Amitriptyline12

Dietary riboflavin deficiency is known to diminish malarial parasitemia. In this study, we determined whether imipramine and amitriptyline, drugs which inhibit riboflavin metabolism, have antimalarial efficacy. In addition, we evaluated whether these drugs, like other antimalarial agents, increase the hemolytic response to ferriprotoporphyrin IX (FP). The growth of Plasmodium falciparum (FCR3) in the absence and presence of these drugs (10 to 75 μM) was measured by determining (³H)hypoxanthine uptake by intraerythrocytic parasites for 48 h in RPMI 1640 medium. The uptake of (³H)hypoxanthine was significantly reduced in a dose-dependent manner by both imipramine and amitriptyline. The IC₅₀ values of imipramine and amitriptyline at 48 h were 56 and 45 μM, respectively. Both drugs enhanced hemolysis induced by FP (10 or 20 μM). No hemolysis by these drugs was detected in the absence of FP. It is concluded that the tricyclic antidepressants, imipramine and amitriptyline, possess substantial antimalarial properties.     

Enhanced Uptake and Metabolism of Riboflavin in Erythrocytes Infected with Plasmodium falciparum

Riboflavin deficiency inhibits the growth of malaria parasites both in vitro and in vivo in infected animals and humans. Although the precise mechanisms underlying this inhibition are unknown, they may involve enhanced requirements for riboflavin by parasites. To investigate this possibility, the rate of uptake of [¹⁴C]riboflavin and the biosynthesis of FMN and FAD from riboflavin were studied in infected (5–8% parasitemia) and uninfected human erythrocytes. All cells were incubated for 0–3 h at 37° C in phosphate buffered saline containing MgCl₂, glucose, and [¹⁴C]riboflavin (2.5–7.5 μM). At hourly intervals, samples were removed, centrifuged, washed twice with cold buffer, and lysed before counting the radioactivity. The rate of in vitro biosynthesis of FMN and FAD from riboflavin in erythrocytes was measured by ion exchange chromatography and reverse isotope dilution techniques. Results showed that the rate of riboflavin uptake and the biosynthesis of FMN and FAD were enhanced in erythrocytes with parasitemia as compared with results in unparasitized erythrocytes. Riboflavin uptake in erythrocytes was proportional to the extent of parasitemia and especially to percent of schizonts present in erythrocytes. These studies indicate that the requirement for riboflavin may be greater in the parasite than in the host erythrocyte. This increased riboflavin requirement may be due to rapid multiplication, higher metabolic rate, and extreme vulnerability to oxidative stress of malaria parasites compared with that of host erythrocytes. The differential requirement of riboflavin by the host and the malaria parasite may hold important potential for developing new strategies for malaria chemotherapy.     

Macromolecular composition of Palaeozoic scolecodonts: insights into the molecular taphonomy of zoomorphs

Dutta, S., Hartkopf‐Fröder, C., Mann, U., Wilkes, H., Brocke, R. & Bertram, N. 2010: Macromolecular composition of Palaeozoic scolecodonts: insights into the molecular taphonomy of zoomorphs. Lethaia, Vol. 43, pp. 334–343. Biogeochemistry and molecular taphonomy of biopolymers of marine zoomorphs are poorly known. In order to obtain insights into this issue we report on the biogeomacromolecular composition of hand‐picked, well‐preserved scolecodonts of Ordovician, Silurian and Devonian age using micro‐Fourier transform infrared (micro‐FTIR) spectroscopy, Curie point pyrolysis‐gas chromatography‐mass spectrometry (Cupy‐GC‐MS) and tetramethylammonium hydroxide (TMAH)‐assisted thermochemolysis‐GC‐MS. The present study reveals that scolecodonts are composed of both aliphatic and aromatic moieties. The micro‐FTIR spectra of scolecodonts are characterized by aliphatic CH_x (3000–2800 and 1460–1450/cm) and CH₃ (1375/cm) absorptions and aromatic C=C (1560–1610/cm) and CH (3050/cm and 700–900/cm) absorptions. The major pyrolysis products from the scolecodonts include aromatic hydrocarbons such as alkylbenzenes, alkylnaphthalenes and alkylphenols. Aliphatic hydrocarbons are represented by a homologous series of n‐alkenes and n‐alkanes. The compounds released upon thermochemolysis with TMAH are saturated and unsaturated fatty acids (as their methyl esters), n‐alkenes/alkanes and aromatic acids (as their methyl esters). No protein/amino acid‐derived compounds have been recognized in the pyrolysates or in the thermochemolysates, and it is concluded that protein/amino acid‐related compounds, which are commonly found in the jaws of extant polychaetes, were destroyed due to diagenetic processes. Obviously, excellent morphological preservation and low thermal alteration are not paralleled by a similar degree of chemical preservation. □Biogeomacromolecules, micro‐FTIR, pyrolysis‐GC‐MS, scolecodonts, thermochemolysis‐GC‐MS.     

Ontogenic variation in nitrogen assimilation,nodulation and nitrogen fixation in groundnut (Arachis hypogaea) genotypes*

Seasonal pattern of acetylene reduction (AR) and shoot nitrogen accumulation was studied in nine groundnut cultivars. Shoot N accumulation by all the cultivars was maintained until shortly before maturity and it occurred faster over the reproductíve growth phase than over the earlier phases. In all cultivars plant AR (PAR) did not reflect this pattern of N accumulation, being greater over the vegetative and pod initiation phases. This suggests that the commonly observed low PAR values for groundnut over the reproductive growth phase may be the result of factors other than sink competition. There were significant interactions of cultivar with stage of crop growth for PAR, nodule mass, and specific nitrogenase activity (SNA). Virginia types generally showed better nodulation, higher N₂-fixing capacity (both PAR and SNA) than valencias, and significant differences were observed between cultivars within a botanical type.     

Sensitivity and Resistance to Growth Promoting Agents in Animal Lactobacilli

The minimal inhibitory concentrations of 11 growth promoting agents were determined by agar-dilution method against 113 strains of lactobacilli isolated from caeca of pigs, cattle and poultry. Only Lactobacillus acidophilus strains were susceptible to avoparcin and all strains were resistant to copper sulphate. Resistance was noted in cattle and poultry strains against bacitracin, in pig strains against virginiamycin, and in pig and poultry strains against nitrovin. Resistance against carbadox, flavomycin, lincomycin, oleandomycin, spiramycin and tylosin was noted in strains from all three host species.     

Potential carbon release from permafrost soils of Northeastern Siberia

Permafrost soils are an important reservoir of carbon (C) in boreal and arctic ecosystems. Rising global temperature is expected to enhance decomposition of organic matter frozen in permafrost, and may cause positive feedback to warming as CO₂ is released to the atmosphere. Significant amounts of organic matter remain frozen in thick mineral soil (loess) deposits in northeastern Siberia, but the quantity and lability of this deep organic C is poorly known. Soils from four tundra and boreal forest locations in northeastern Siberia that have been continuously frozen since the Pleistocene were incubated at controlled temperatures (5, 10 and 15°C) to determine their potential to release C to the atmosphere when thawed. Across all sites, CO₂ with radiocarbon (¹⁴C) ages ranging between～21 and 24 ka bp was respired when these permafrost soils were thawed. The amount of C released in the first several months was strongly correlated to C concentration in the bulk soil in the different sites, and this correlation remained the same for fluxes up to 1 year later. Fluxes were initially strongly related to temperature with a mean Q₁₀ value of 1.9±0.3 across all sites, and later were unrelated to temperature but still correlated with bulk soil C concentration. Modeled inversions of Δ¹⁴CO₂ values in respiration CO₂ and soil C components revealed mean contribution of 70% and 26% from dissolved organic C to respiration CO₂ in case of two permafrost soils, while organic matter fragments dominated respiration (mean 68%) from a surface mineral soil that served as modern reference sample. Our results suggest that if 10% of the total Siberian permafrost C pool was thawed to a temperature of 5°C, about 1 Pg C will be initially released from labile C pools, followed by respiration of～40 Pg C to the atmosphere over a period of four decades.