Further farnesyl-homogentisic acid derivatives from Otoba parvifolia

The seeds of Otoba parvifolia contain three novel compounds apparently derived from homogentisic acid, rel-(1′R,5′R)-2-(1′-farnesyl-5′-hydroxy-2′-oxocyclohex-3′-en-1′-yl)-acetic acid and its acetate as well as rel-(1′R,4′S,5′R)-2-(1′-farnesyl-4′,5′-dihydroxy-2′-oxocyclohexan-1′-yl)-acetic acid δ-lactone. The structure of an additional isolate, previously described as 2-(1′-farnesyl-2′-hydroxy-5′-oxocyclohex-3′-en-1′-yl)-acetic acid γ-lactone was revised to rel-(1′R,5′R)-2-(1′-farnesyl-5′-hydroxy-2′-oxocyclohex-3′-en-1′-yl)-acetic acid δ-lactone.     

Dihydrochalcones, coumarins and alkaloids from Metrodorea nigra

Two novel dihydrochalcones, 2′,3,4′,6′-tetrahydroxy-4-methoxy-3′,5-di-(3,3-dimethylallyl)-dihydrochalcone and 2′,.3,6′-trihydroxy-4-methoxy-5-(3,3-dimethylallyl)-3′,4′-(2″,2″-dimethyldihydropyran)-dihydrochalcone, have been isolated from fresh fruits of Metrodorea nigra. Stems and leaves showed a similar composition and we have isolated common steroids, simple coumarins, several furocoumarins, furoquinoline alkaloids and a furofuran lignan. From stems, we have also isolated the pentacyclic 6-C-monoterpenyl-5,7-dioxycoumarin, deoxybruceol. Structures of the isolated compounds were elucidated on the basis of spectral data.     

Ligand-Induced Translocation of Epidermal Growth Factor Receptor to the Nucleus of NR6/HER Fibroblasts Is Serum Dependent

Ligand-induced translocation of epidermal growth factor receptors (EGF-R) to the nucleus of NR6/HER fibroblasts has been studied by immunoelectron microscopy. Following treatment of NR6/HER cells with epidermal growth factor (EGF) for 1 h, there was a decrease in EGF-R labeling at the plasma membrane and a corresponding increase in EGF-R in the nucleus. This was preceded by a rapid and sustained increase in nuclear phosphotyrosine content, detectable within 2 min of EGF treatment. EGF-R translocation into the nucleus was completely prevented by 18 h serum starvation prior to treatment with EGF. These results indicate that translocation of EGF-R to the nucleus is a controlled process and they suggest theft EGF-R may directly influence nuclear function.     

Extracellular polysaccharide of Nostoc commune (Cyanobacteria) inhibits fusion of membrane vesicles during desiccation

Cells of the cyanobacterium Nostoc commune secrete a complex, high molecular weight, extracellular polysaccharide (EPS) which accumulates to more than 60% of the dry weight of colonies. The EPS was purified from the clonal isolate N. commune DRH1. The midpoint of the membrane phase transition (T_m) of desiccated cells of N. commune CHEN was low (T_{m dry} = 8 °C) and was comparable to the T_m of rehydrated cells((T_m)_H20 = 6 °C). The EPS was not responsible for the depression of T_m. However, the EPS, at low concentrations, inhibited specifically the fusion of phosphatidylcholine membrane vesicles when they were dried in vitro at0% relative humidity (−400 MPa). Low concentrations of a trehalose:sucrose mixture, in a molar ratio which corresponded with that present in cells in vivo, together with small amounts of the EPS, were efficient in preventing leakage of carboxyfloroscein (CF) from membrane vesicles. Freeze-fracture electron microscopy resolved complex changes in the structure of the EPS and the outer membrane in response to rehydration of desiccated cells. The capacity of the EPS to prevent membrane fusion, the maintenance of a low T_{m dry} in desiccated cells, and the changes in rheological properties of the EPS in response to water availability, constitute what are likely important mechanisms for desiccation tolerance in this cyanobacterium. This revised version was published online in August 2006 with corrections to the Cover Date.     

Polyamine derivatives as inhibitors of trypanothione reductase and assessment of their trypanocidal activities

Trypanothione reductase (TR) occurs exclusively in trypanosomes and leishmania, which are the etiological agents of many diseases. TR plays a vital role in the antioxidant defenses of these parasites and inhibitors of TR have potential as antitrypanosomal agents. We describe the syntheses of several spermine and spermidine derivatives and the inhibiting effects of these compounds on T. cruzi TR. All of the inhibiting compounds displayed competitive inhibition of TR-mediated reduction of trypanothione disulfide. The three most effective compounds studied were N⁴,N⁸-bis(3-phenylpropyl)spermine (12), N⁴,N⁸-bis(2-naphthylmethyl)spermine (14), and N¹,N⁸-bis(2-naphthylmethyl)spermidine (21), with K_i values of 3.5, 5.5 and 9.5 μM, respectively. Compounds 12, 14, and 21 were found to be potent trypanocides in vitro with IC₅₀ values ranging from 0.19 to 0.83 μM against four T. brucei ssp. strains. However, these compounds did not prolong the lives of mice infected with trypanosomes. This work indicates that certain polyamine derivatives which target a unique pathway in Trypanosomatidae have potential as antitrypanosomal agents.     

Iron supplementation moderates but does not cure the Belgrade anemia

Belgrade rats inherit microcytic, hypochromic anemia as an autosomalrecessive trait (gene symbol b). Erythrocytes and tissue are iron deficientin the face of elevated TIBC (total iron binding capacity) and percent ironsaturation; iron injections increased the number of erythrocytes but theirappearance remained abnormal. We have investigated iron supplements toimprove husbandry of b/b rats and to learn more about the underlying defectand its tissue distribution. Weekly IM (intramuscular) injections ofiron–dextran (Imferon at 30 mg kg) improved the anemia but did not alter thered cell morphology. Certain diets also improved the health of b/b rats whencompared to standard rat chows by the criteria of weight, survival toadulthood, hematology and reproduction. The critical nutritional factorturned out to be iron bioavailability, with ferrous iron added to the dietimproving the health of Belgrade rats without affecting the underlyingerythroid defect. Tissue iron measurements after dietary or parenteralsupplementation confirmed the iron deficient status of untreated b/b rats andestablished that dietary ferrous iron partially relieved this deficiency,with injections leading to greater amounts of tissue iron. Serum iron andTIBC were also found to be elevated in untreated b/b rats, with dietarysupplementation decreasing but not eliminating the elevation in TIBC. Thesestudies indicate that iron supplements can improve the health of b/b ratswithout altering the underlying defect and also suggest that the mutationcould alter iron uptake in the GI (gastrointestinal) tract.     

Respiratory muscle reserve in rats during heavy exercise

Gosselin, Luc E., David Megirian, Joshua Rodman, DonnaMueller, and Gaspar A. Farkas. Respiratory muscle reserve in ratsduring heavy exercise. J. Appl.Physiol. 83(4): 1405-1409, 1997.The extent towhich the respiratory pump muscles limit maximal aerobic capacity inquadrupeds is not entirely clear. To examine the effect of reducedrespiratory muscle reserve on aerobic capacity, whole bodypeak oxygen consumption(O_{2 peak}) wasmeasured in healthy Sprague-Dawley rats before and after Sham,unilateral, or bilateral hemidiaphragm denervation (Dnv) surgery.O_{2 peak} wasdetermined by using a graded treadmill running test.Hemidiaphragm paralysis was verified after testing byrecording the absence of electromyographic activity duringinspiration. Before surgery, O_{2 peak} averaged 86, 87, and 92 ml · kg¹ · min¹for the Sham, unilateral, and bilateral Dnv groups, respectively. Twoweeks after surgery, there was no significant change inO_{2 peak} foreither the Sham or unilateral Dnv group. However,O_{2 peak} decreased~19% in the bilateral Dnv group 2 wk after surgery. These findingsstrongly suggest that the pulmonary system in rats is designed suchthat during heavy exercise, the remaining respiratory pump muscles areable to compensate for the loss of one hemidiaphragm, but not of both.

     

Effect of stimulus strength and adaptation on the thermotactic response of Dictyostelium discoideum pseudoplasmodia

The thermotactic responses of Dictyostelium discoideum strain HL50 and mutants derived from this strain have been characterized by curves of stimulus-strength vs response. With gradient midpoint temperatures of 16 and 24 °C, these curves are typical of those of a single response, i.e., the strength of the response increases with increasing stimulus strength until at some strength the response saturates. However, with a gradient midpoint temperature close to the transition from negative to positive thermotaxis, the sign of the thermotactic response depends on gradient strength. These observations support the hypothesis that the transduction pathways for positive and negative thermotaxis act concurrently and contain separable elements. An investigation of the adaptation of thermotaxis indicated that the stimulus-strength-dependence and midpoint-temperature-dependence of both thermosensory responses was altered by shifting the growth and development temperature.     

Variations in plasma protein components during extracorporeal circulation

In this research we have determined the behaviour of proteic plasmatic pattern and some enzymes during extracorporeal circulation and we noted a constant increase of albumin and of the ratio Alb/Glob. We observed also variations of some enzymes. Our opinion according other AA. is that this changes are determined principally by the large dose of heparin necessary during the C.E.C.