Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiopen-4,9-quinones

Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic diethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimastigote forms of Trypanosoma cruzi in vitro, (2) lysis of trypomastigote forms of T. cruzi in murine blood, (3) growth of Plasmodium falciparum in vitro, and (4) inhibition of the recombinant enzyme trypanothione reducatase. The parent compound, naphtho[2,3-b]thiophen-4,9-quinone (3a), was among the most active quinone tested in vitro against P. falciparum at 0.2 microM. However, it was inactive against P. berghei-infected mice treated with 2.3 mmol/kg daily for 5 days. Most of the quinones prepared were active against T. cruzi epimastigotes in culture but exhibited weak activity at 4 degrees C against trypomastigotes in murine blood as well against the enzyme trypanothione reducatase. Further structural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones.     

A re-investigation of questionable subclassifications of presynaptic alpha2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

It has been suggested that at least the majority of mammalian presynaptic alpha2-autoreceptors belong to the genetic alpha2A/D-adrenoceptor subtype. The aim of the present study was to re-examine the alpha2-autoreceptors in tissues in which previous assignments conflicted with this alpha2A/D rule: in the rat vena cava and rat heart atria, where the autoreceptors were classified as alpha2B or similar to, but not identical with, alpha2D, and in the human kidney, where they were classified as alpha2C. Also re-examined were the autoreceptors in the guinea-pig urethra, where they were suggested to be alpha2A, in agreement with the rule, but in contrast to indications that the alpha2A/D-adrenoceptor of the guinea pig possesses alpha2D pharmacological properties. Tissue pieces were preincubated with 3H-noradrenaline and then superfused and stimulated electrically under autoinhibition-free or almost autoinhibition-free conditions. The Kd values of up to 14 antagonists (including the partial agonist oxymetazoline) against the release-inhibiting effect of the alpha2 agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) were determined. UK 14,304 reduced the evoked overflow of tritium with an EC50 between 6.3 and 13.2 nM. All antagonists (except prazosin in one case) shifted the concentration-inhibition curve of UK 14,304 to the right. Comparison of the Kd values thus obtained with Kd values at known alpha2 subtypes indicated that the autoreceptors in the rat vena cava, rat atria and the guinea-pig urethra were alpha2D and those in the human kidney alpha2A. For example, the pKd values of the antagonists in the rat vena cava, in rat atria and in the guinea-pig urethra were closely correlated with pKd values at the prototypic alpha2D radioligand binding sites in the bovine pineal gland (r = 0.96, P < 0.001; r = 0.92, P < 0.01; and r = 0.95; P < 0.001) and with the pKd values at the alpha2D-autoreceptors of guinea-pig atria (r = 0.99, P < 0.001; r = 0.95, P < 0.001; and r = 0.98, P < 0.001). The pKd values at the autoreceptors in rat vena cava, rat atria and guinea-pig urethra were not significantly or more loosely correlated with pKd values at alpha2A, alpha2B and alpha2C binding sites and alpha2A-autoreceptors. On the other hand, the pKd values of the antagonists in the human kidney were closely correlated with pKd values at the prototypic alpha2A radioligand binding sites in HT29 cells (r = 0.95; P < 0.001) and with pKd values at the alpha2A-autoreceptors of the pig brain cortex (r = 0.97; P < 0.001), but were not significantly or more loosely correlated with pKd values at alpha2B, alpha2C and alpha2D binding sites and alpha2D-autoreceptors. In contrast to previous suggestions, the autoreceptors in rat vena cava and atria are alpha2D, those in the human kidney alpha2A, and those in the guinea-pig urethra equally alpha2D. All, therefore, conform to the rule that alpha2-autoreceptors belong at least predominantly to the genetic alpha2A/D subtype of the alpha2-adrenoceptor. The apparent paradox of an alpha2A-autoreceptor in the urethra of the guinea pig, a species in which the genetic alpha2A/D-adrenoceptor otherwise has alpha2D pharmacological properties, is removed.     

Oxidative stability of extra virgin olive oil blended with sesame seed oil during storage: an optimization study based on combined design methodology

In this study, extra virgin olive oil (EVOO) was mixed with sesame seed oil (SSO) at different concentrations (100:0, 90:10, 80:20, 70:30 and 60:40 w/w) and stored for 90 days at room conditions. To see the effect of mixing level and storage period, a combined design having two mixtures (EVOO and SSO) and one process factor (storage period) was used. Main oxidation parameters (free fatty acid content, refractive index, peroxide value and p-anisidine value) and major fatty acid composition of the samples were characterized. It was observed that EVOO is quite sensitive to oxidation compared to SSO and increase of SSO in the blended oil samples decreased the oxidation of the product during storage. Major fatty acids were palmitic, oleic and linoleic acids. Addition of SSO caused a significantly change in the fatty acid composition. The results showed that EVOO could be stored for longer time by mixing of SSO having strong antioxidant activity.     

Controller design and performance evaluation for deadlock avoidance in automated flexible manufacturing cells

In this paper, the design of a deadlock avoidance controller is described. The uncontrolled system is modeled using colored Petri nets. The system controller is based on a restrictive (not maximally permissive) deadlock avoidance policy to resolve deadlocks and control the real-time resource allocation decisions in the system. Performance evaluation of systems controlled by not maximally permissive algorithms is essential in determining the applicability and effectiveness of the control algorithms. The performance of the controlled system is compared with performance of optimal control policies to quantify the effects of the restrictiveness of the deadlock avoidance policy on system performance.     

Apolipoprotein E allele frequencies in argyrophilic grain disease

Glanzmann's thrombasthenia is a rare inherited hematological disorder defined by deficiency or abnormality of the glycoprotein (GP) IIb-IIIa complex. Presenting symptoms are hemorrhagic events, mainly epistaxis, purpura, or menorrhagia. We describe the clinical course and management of a 14-year-old girl with Glanzmann's thrombasthenia and severe menorrhagia. Following treatment with 20 U of packed red blood cells, 37 U of platelets, 7 U of fresh frozen plasma, cryoprecipitate, intravenous estrogens, and methylergotrine maleate with no improvement, the uterine cavity was packed for 48 hr. This unusual procedure halted the bleeding and avoided the necessity for a hysterectomy. When treating acute menorrhagia in patients with Glanzmann's thrombasthenia, the physician should be familiar with the characteristics and all treatment modalities for this disorder.     

Gender affects rats' central nervous system histaminergic responses to dietary manipulation

The histaminergic system (histamine and its H1-receptor) of the central nervous system has been implicated in control of food intake. The reported studies were designed to examine the effects of food restriction and very low (1%) protein diets on central nervous system H1-receptors in male and female rats. In a series of experiments, groups of rats were freely fed a 25% protein diet, a 1% protein diet, or fed the 25% protein diet at 4 g/100 g body weight for 14-20 d. When freely fed 25% protein diets, females had higher whole-brain H1-receptor binding than males on d 1 (female 122.36 +/- 4.53 and male 65.78 +/- 3.82 pmol/g protein; P < 0.001). Changing diets affected central H1-receptor binding in both males and females (P < 0.003). When rats were fed both restricted levels of food and 1% protein diets, the receptor binding of males increased by d 5 whereas that of females decreased by d 5 (P < 0.001). When fed 1% protein diets, females had decreased H1-receptor binding (98.4 +/- 2.38 pmol/g protein) and that in males increased to 119.81 +/- 5.09 pmol/g protein. After 15 d, females had eaten significantly more food than males: females 166 +/- 4.9 g, males 124 +/- 1.9 g (P< 0.0007). Males had a significantly greater weight loss than females: males -28.8 +/- 2.6 g, females -17.08 +/- 0.97 g (P < 0.0007). When fed restricted diets, females had decreased H1-receptor binding (93.81 +/- 5.58 pmol/g) whereas binding in males increased to 111.27 +/- 8.55 pmol/g. Preliminary saturation binding studies indicated that restricted food intake lowered receptor density (females consuming 25% protein: 715 +/- 30 pmol/g protein; female restricted: 467 +/- 28 pmol/g protein, P < 0.05), while 1% protein increased receptor sensitivity, i.e., lowered KD (males consuming 25% protein: 15.3 +/- 1.8 nmol; males fed low protein: 2.8 +/- 0.27 nmol). This study suggests that dietary manipulation affects central H1-receptor binding in a gender-specific manner, thereby modulating central histaminergic activity during food or protein deficit.     

Inflammatory pseudotumour of the trachea: report of a case in an eight-year-old child

A polypoid inflammatory pseudotumour was diagnosed in the trachea of an eight-year-old child who presented with asthmatic symptoms. The tumour showed 80 per cent blockage of the lower trachea and consisted of proliferating spindly fibroblastic cells admixed with a variable number of inflammatory cells. The literature on childhood inflammatory pseudotumours is reviewed together with the differential diagnosis of other polypoid mesenchymal tumours of the trachea.     

Color vision tests for early detection of antiepileptic drug toxicity

A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.