Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine onTrypanosoma cruzi

Summary The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes ofTrypanosoma cruzi, at concentrations lower than 100 M, and motility and infectivity of the bloodstream trypomastigote form at 200 M. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 M TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.     

A deficiency of the homeotic complex of the beetle Tribolium

In Drosophila, the establishment of regional commitments along most of the anterior/posterior axis of the developing embryo depends on two clusters of homeotic genes: the Antennapedia complex (ANT-C) and the bithorax complex (BX-C). The red flour beetle has a single complex (HOM-C) representing the homologues of the ANT-C and BX-C in juxtaposition. Beetles trans-heterozygous for two particular HOM-C mutations spontaneously generate a large deficiency, presumably by an exchange within the common region of two overlapping inversions. Genetic and molecular results indicate that this deficiency spans at least the interval between the Deformed and abdominal-A homologues. In deficiency homozygous embryos, all gnathal, thoracic and abdominal segments develop antennal appendages, suggesting that a gene(s) has been deleted that acts to distinguish trunk from head. There is no evidence that beetles have a homologue of the segmentation gene fushi tarazu of similar genomic location and function. On the basis of the genetic tractability, convenient genome size and organization of Tribolium, and its relatively long phylogenetic divergence from Drosophila (>300 million years), we have integrated developmental genetic and molecular analyses of the HOM-C. We isolated about 70 mutations in the complex representing at least six complementation groups. The homeotic phenotypes of adults and lethal embryos lead us to believe that these beetle genes are homologous with the Drosophila genes indicated in Fig. 1 (see text).     

The phytotoxins ofMycosphaerella fijiensis,the causative agent of Black Sigatoka disease of bananas and plantains

Black Sigatoka is the most costly to control disease of bananas and plantains in the world. Currently, a worldwide search is underway either to find or to produce cultivars that are disease-resistant or-tolerant. Phytotoxins isolated from the pathogen might facilitate the discovery of such cultivars. Several aromatic compounds from liquid cultures ofMycosphaerella fijiensis, the causal agent of Black Sigatoka disease of bananas and plantains, have been isolated. The most abundant and phytotoxic of these compounds is 2,4,8-trihydroxytetralone, which induces necrotic lesions at 5 g/5 l in less than 12 h on sensitive cultivars of bananas. This compound exhibits host-selectivity that mimics that of the pathogen. Other phytotoxins isolated from this fungus, in lesser amounts, were juglone, the novel compound 2-carboxy-3-hydroxycinnamic acid, isoochracinic acid and 4-hydroxyscytalone. Some of the phytotoxins isolated are melanin shunt pathway metabolites, which makes this fungus unique among plant pathogens.     

Identification and possible biological relevance of spermatozoal transglutaminase

Summary Normal human spermatozoa were demonstrated by dot immunoblot analysis and immunohistochemistry to possess transglutaminase (TGase). The immunological identification of spermatozoal TGase is consistent with reports by others of its biochemical identification and suggested role in sperm motility,and provides, in view of the immunoregulatory properties of seminal plasma TGase, presumptive identification of a means whereby spermatozoa, under normal physiological conditions, may possibly be protected from immunological attack within the female reproductive tract.     

Effect of feeding cereal-legume diets to rats on in vitro absorption of45Ca

Summary The in vitro absorption of calcium from the duodenum was significantly less in a group of rats fed on a wheat diet than in a group fed a wheat and Bengal gram (7030) diet.     

Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature

Summary Histamine content in the rat hypothalamus was lower at 4°C and higher at 31°C compared to that at 21°C. Pretreatment with -fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, attenuated both the increased level of hypothalamic histamine and rat adaptive behavior at 31°C. Increase of histamine content in the hypothalamus appears to be an important factor contributing to rat adaptive behavior to high environmental temperature.     

Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

Summary Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp--phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA₂=7.6, n=0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [³H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [³H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons.     

Gigantecin: A novel antimitotic and cytotoxic acetogenin,with nonadjacent tetrahydrofuran rings,fromGoniothalamus giganteus (Annonaceae)

Summary Gigantecin (I), a novel tetrahydroxy-di-tetrahydrofuran fatty acid -lactone (acetogenin), was isolated from an ethanolic extract of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae), by means of activity-directed fractionation (brine shrimp lethality test). This new compound is extremely cytotoxic to human tumor cells, inhibits crown gall tumors on potato discs, and is active in an assay designed to detect antimitotic agents (9 ASK).