Synthesis and fungicidal activity of 2,2′-bipyridine derivatives

A series of substituted 2,2′-bipyridine derivatives was prepared using the Kröhnke reaction and alkylation of 4,4′-dimethyl-2,2′-bipyridine. These compounds were screened for fungicidal activity against 9 plant diseases. 5-Phenyl-2,2′-bipyridine exhibited strong preventative and curative fungicidal activity against wheat powdery mildew (Erisyphe graminis) and wheat leaf rust (Puccinia recondita).     

Ectopic ACTH syndrome

Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4–6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.     

Gating of gap junction channels.

Gap junctional conductance ( gj ) in various species is gated by voltage and intracellular pH (pHi). In amphibian embryos, gj is reduced to half by a 14 mV transjunctional voltage ( Vj ), a change that in fish embryo requires approximately 28 mV. Crayfish septate axon and pairs of dissociated rat myocytes show no voltage dependence of gj over a range of Vj greater than +/- 50 mV. In fish and amphibian blastomeres , gj is steeply decreased by decrease in pHi (n, Hill coefficient: 4.5) and the apparent pKH (7.3) is in the physiological range. In crayfish septate axon the pKH is lower (6.7) and the curve is less steep (n = 2.7). Rises in cytoplasmic Ca can also decrease gj but much higher concentrations are required (greater than 0.1 mM in fish blastomeres). Voltage and pH gates on gap junctions in amphibian embryos appear independent. In squid blastomeres pH gates exhibit some sensitivity to potential, both transjunctional and between inside and outside. A pharmacology of gap junctions is being developed: certain agents block gj directly (aldehydes, alcohols, NEM in crayfish); others block by decreasing pHi (esters that are hydrolyzed by intrinsic esterases, NEM in vertebrates, and, as in the experiments demonstrating the effect of pHi, weak acids). Certain agents block pH sensitivity without affecting voltage dependence (retinoic acid, glutaraldehyde, EEDQ), further indicating separateness of pH and voltage gates. These studies demonstrate a dynamics of gap junctional conductance and variability in gating in a series of possibly homologous membrane channels.     

Trypanosoma cruzi: strain selection by different schedules of mouse passage of an initially mixed infection

From an initial double infection in mice, established by simultaneous and equivalent inocula of bloodstream forms of strains Y and F of Trypanosoma cruzi, two lines were derived by subinoculations: one (W) passaged every week, the other (M) every month. Through biological and biochemical methods only the Y strain was identified at the end of the 10th and 16th passages of line W and only the F strain at the 2nd and 4th passages of line M. The results illustrate strain selection through laboratory manipulation of initially mixed populations of T. cruzi.     

Isolation and properties of flagella of trypanosomatids.

A procedufe is described for the isolation of flagella of Crithidia fasciculata, Herpetomonas samuelpessoai and Leishmania tarentolae in a highly purified state and giving reasonably good yield. The 3 types of flagella give a similar electrophoretic pattern of proteins. It is shown that H. samuelpessoai and, to a lesser extent, C. fasciculata flagella confer protection against Trypanosoma cruzi infection.     

Prenylated flavonoids from seeds of Calopogonium mucunoides

The seeds of Calopogonium mucunoides furnished 7-O-γ,γ-dimethylallyl-8-methoxy-3′,4′-dioxymethylene-isoflavone, 7-O-γ,γ-dimethylallyl-3′-hydroxy-4′-methoxyisoflavone, 7-O-γ,γ-dimethylallyl-3′,4′-dimethoxyisoflavone and 2S-di[6′',6′'-dimethylpyrano (2′',3′':7,8;2′',3′':4′,3′)]-flavanone whose structures were established by spectroscopic means involving the use of 400 MHz ¹H NMR with double irradiation and INDOR techniques.     

Lack of effect of toxic aluminium concentrations on nitrogen fixation by nodulatedStylosanthes species

Summary Effects of three solution aluminium concentrations (0, 25, and 100M) on nitrogen fixation by well-nodulated plants ofStylosanthes hamata, Stylosanthes humilis andStylosanthes scabra are reported. Plants were inoculated with Rhizobium CB756 and grown for 21 days in an aluminium-free nutrient solution at pH 5.3 before imposition of the aluminium treatments.Nitrogen fixation was measured both by the increase in total nitrogen content of the plants and acetylene reduction in roots of plants harvested at 10 and 20 days after imposition of the aluminium treatments. Solution aluminium concentrations as high as 100M, had no detrimental effect on nitrogen fixation in any species.     

Effect of temperature on the reversal of the calcium ion pump in sarcoplasmic reticulum.

Sarcoplasmic-reticulum vesicles were actively loaded with Ca2+ in the presence of phosphate, and the ADP-induced Ca2+ efflux and ATP synthesis were measured as a function of temperature. Arrhenius plots show break points for both processes at about 18 and 37 degrees C. Between 18 and 37 degrees C, Ca2+ efflux and ATP synthesis occur with an activation energy of 67.2-71.4 kJ/mol, whereas it is about 189-210 kJ/mol for temperatures below 18 degrees C. Above 37 degrees C, the rates of ADP-induced Ca2+ release and of ATP synthesis sharply decline until the temperature reaches about 42 degrees C. Above this temperature, the Ca2+ efflux increases again even in absence of ADP, although the synthesis of ATP is inhibited, which reflects leakiness of the vesicles. The results show that the transition temperatures for ADP-induced Ca2+ efflux and for ATP synthesis resemble those for active Ca2+ uptake, which indicates that the same coupling mechanism is involved during the inward and outward Ca2+ translocations across the membrane.     

Fluxes of Ca2+, Sr2+ and Mg2+ in synaptosomes.

Synaptosomes isolated from sheep brain cortex accumulate Ca²⁺, Sr²⁺ and Mg²⁺ when incubated in isosmotic sucrose media containing 5 mM of either of these cations. The maximal levels of cations retained per mg of protein are 100 nmol of Ca²⁺, 85 nmol of Mg²⁺ and 80 nmol of Sr²⁺. The loss of Ca²⁺ or Sr²⁺ from the preloaded synaptosomes is increased by monovalent cations in the following order: Na⁺> K⁺ > Li⁺> choline, whereas for the loss of Mg²⁺ this order is different: K⁺ > Na⁺ > Li ～ choline. The efflux of Ca²⁺ or Sr²⁺ induced by monovalent cations decreases as the temperature is lowered and it is nearly abolished at 0°C, whereas the efflux of Mg²⁺ is much less influenced by temperature. The results suggest that the mechanism of exchange of Ca²⁺ for Na⁺ in synaptosomes operates similarly for Sr²⁺, but not for Mg²⁺.