5-Amidinobenzo[b]thiophenes as dual inhibitors of factors IXa and Xa

Syntheses and SAR studies of 5-amidinobenzo[b]thiophene analogs provided compounds with low submicromolar factor IXa activity and equal or slightly better selectivity relative to factor Xa.     

Relationship between dental morphology, sex, body length and age in Pontoporia blainvillei and Sotalia fluviatilis (Cetacea) in Northern Rio de Janeiro, Brazil

The relationship between dental morphology, sex, body length and age of small cetaceans can be used to determine ontogeny, sexual dimorphism and geographical variation. The objective of this study was to determine the relationship between dental morphology, sex, body size and age. A total of 91 specimens of P. blainvillei and 80 specimens of S. fluviatilis accidentally captured in fisheries or stranded in northern Rio de Janeiro (21 masculine37'-22 masculine25'S), from September 1988 to November 1996 were analysed. The teeth root diameter in P. blainvillei was significantly different between the sex; the values for females were larger than males. In neither species aid we observed significant in variations dimension and number of teeth, thickness of dentine and cemental layers and in the maximum width of cement as a function of body size. Age was related to increases in tooth length, root and cingulum diameters, and maximum width of cement in individuals of P. blainvillei, and tooth and crown lengths and maximum width of cement in individuals of S. fluviatilis. The observation of a linear growth between maximum width of cement and age in both species indicates that the equations obtained can be used to estimate relative age in P. blainvillei and S. fluviatilis in northern of Rio de Janeiro.     

Chromosomal localization of satellite DNA sequences among 22 species of felids and canids (Carnivora)

In situ hybridization was carried out using cloned satellite DNAs from the domestic cat and domestic dog as probes to metaphase chromosomes from 12 species of felids and 10 species of canids. Autoradiographic silver grains along metaphase chromosomes were counted and analyzed with regard to the mean number of grains per cell in each species, their chromosomal location, and their presence or absence on specific autosomes or sex chromosomes, where known. Among the felids and canids there was a 7.6- and 8.9-fold statistically significant difference, respectively, in the mean number of grains per cell between the species having the minimum and maximum values. Among the felids, most grains occurred on the telomeres of D- and E-group chromosomes, although departures from this general pattern also occurred. For example, the Asian golden cat and the Bornean bay cat showed substantial labeling at the centromeric region of chromosome A1, and a number of species showed some labeling at the short-arm telomeres of B-group chromosomes. Among the canids, about 90% of all grains were located at autosomal centromeres, and grains were absent from the sex chromosomes. Grains are usually distributed at chromosomal locations that stain C-band positive; however, certain C-band-positive regions without grains probably do not contain the particular satellites studied here.     

A note on the use of cross-linked starch in microbiology with special reference to detecting amylase production

Anilogel-E, a cross-linked starch, can be used with distinct advantages where native starch or soluble starch are conventionally used, e.g. in scoring for amylolytic organisms, as an ingredient of fermentation media, and in enhancing protoplast regeneration. It is particularly useful for the direct visualization of amylase producing micro-organisms on solid media, making prior replication of colonies unnecessary.     

Computer calculation-based quantitative structure-activity relationships for the oxidation of phenol derivatives horseradish peroxidase compound II

 The second-order rate constants for the oxidation of a series of phenol derivatives by horseradish peroxidase compound II were compared to computer-calculated chemical parameters characteristic for this reaction step. The phenol derivatives studied were phenol, 4-chlorophenol, 3-hydroxyphenol, 3-methylphenol, 4-methylphenol, 4-hydroxybenzoate, 4-methoxyphenol and 4-hydroxybenzaldehyde. Assuming a reaction of the phenolic substrates in their non-dissociated, uncharged forms, clear correlations (r = 0.977 and r = 0.905) were obtained between the natural logarithm of the second-order rate constants (ln k _app and ln k ₂ respectively) for their oxidation by compound II and their calculated ionisation potential, i.e. minus the energy of their highest occupied molecular orbital [E(HOMO)]. In addition to this first approach in which the quantitative structure-activity relationship (QSAR) was based on a calculated frontier orbital parameter of the substrate, in a second and third approach the relative heat of formation (ΔΔHF) calculated for the process of one-electron abstraction and H^• abstraction from the phenol derivatives was used as a parameter. Plots of the natural logarithms of the second-order rate constants (k _app and k ₂) for the reaction and the calculated ΔΔHF values for the process of one-electron abstraction also provide clear QSARs with correlation coefficients of –0.968 and –0.926 respectively. Plots of the natural logarithms of the second-order rate constants (k _app and k ₂) for the reaction and the calculated ΔΔHF values for the process of H^• abstraction provide QSARs with correlation coefficients of –0.989 and –0.922 respectively. Since both mechanisms considered, i.e. initial electron abstraction versus initial H^• abstraction, provided clear QSARs, the results could not be used to discriminate between these two possible mechanisms for phenol oxidation by horseradish peroxidase compound II. The computer calculation-based QSARs thus obtained for the oxidation of the various phenol derivatives by compound II from horseradish peroxidase indicate the validity of the approaches investigated, i.e. both the frontier orbital approach and the approach in which the process is described by calculated relative heats of formation. The results also indicate that outcomes from computer calculations on relatively unrelated phenol derivatives can be reliably compared to one another. Furthermore, as the actual oxidation of peroxidase substrates by compound II is known to be the rate-limiting step in the overall catalysis by horseradish peroxidase, the QSARs of the present study may have implications for the differences in the overall rate of substrate oxidation of the phenol derivatives by horseradish peroxidase. Received: 29 March 1996 / Accepted: 17 July 1996     

Chronic olanzapine treatment decreases arachidonic acid turnover and prostaglandin E₂ concentration in rat brain

The atypical antipsychotic, olanzapine (OLZ), is used to treat bipolar disorder, but its therapeutic mechanism of action is not clear. Arachidonic acid (AA, 20:4n-6) plays a critical role in brain signaling and an up-regulated AA metabolic cascade was reported in postmortem brains from bipolar disorder patients. In this study, we tested whether, similar to the action of the mood stabilizers lithium, carbamazepine and valproate, chronic OLZ treatment would reduce AA turnover in rat brain. We administered OLZ (6 mg/kg/day) or vehicle i.p. to male rats once daily for 21 days. A washout group received 21 days of OLZ followed by vehicle on day 22. Two hours after the last injection, [1-1?C]AA was infused intravenously for 5 min, and timed arterial blood samples were taken. After the rat was killed at 5 min, its brain was microwaved, removed and analyzed. Chronic OLZ decreased plasma unesterified AA concentration, AA incorporation rates and AA turnover in brain phospholipids. These effects were absent after washout. Consistent with reduced AA turnover, OLZ decreased brain cyclooxygenase activity and the brain concentration of the proinflammatory AA-derived metabolite, prostaglandin E?, In view of up-regulated brain AA metabolic markers in bipolar disorder, the abilities of OLZ and the mood stabilizers to commonly decrease prostaglandin E?, and AA turnover in rat brain phospholipids, albeit by different mechanisms, may be related to their efficacy against the disease.     

Thyroid Hormone Treatments Differentially Affect the Temperature Kinetics Properties of FoF1 ATPase and Succinate Oxidase as well as the Lipid/Phospholipid Profiles of Rat Kidney Mitochondria: A Correlative Study

Effect of thyroidectomy (Tx) and subsequent treatment with 3,5,3′-triiodo-l-thyronine (T₃) or replacement therapy (T_R) with T₃ + l-thyroxine (T₄) on the temperature kinetics properties of FoF₁ adenosine triphosphatase (ATPase, ATP synthase, H⁺-translocating ATP synthase EC 3.6.3.14) and succinate oxidase (SO) and on the lipid/phospholipid makeup of rat kidney mitochondria were examined. Tx lowered ATPase activity, which T₃ treatment restored. SO activity was unchanged in Tx but decreased further by T₃ treatment. T_R restored both activities. The energies of ATPase activation in the high and low temperature ranges (E _H and E _L) increased in the Tx and T₃ animals with decrease in phase transition temperature (Tt). T_R restored E _H and E _L but not Tt to euthyroid levels. E _H and E _L of SO decreased in Tx animals. T₃ and T_R restored E _H whereas E _L was restored only in the T_R group; Tt increased in both groups. Total phospholipid and cholesterol contents decreased significantly in Tx and T₃-treated animals. In Tx animals, sphingomyelin (SPM) and phosphatidylcholine (PC) components decreased, while phosphatidylserine (PS) and diphosphatidylglycerol components increased. T₃ and T_R treatments caused decreases in SPM, phosphatidylinositol and PS. PC and phosphatidylethanolamine (PE) increased in the T₃ group. T_R resulted in increased lysophospolipids and PE. Changes in kinetic parameters of the two enzymes were differently correlated with specific phospholipid components. Both T₃ and T_R regimens were unable to restore normal membrane structure-function relationships.     

Treatment of spentwash using chemically modified bagasse and colour removal studies

Studies were carried out on derivatisation of bagasse into an ion exchange material and application of this chemically modified bagasse in the treatment of distillery wastewater. It was found that CHPTAC bagasse with HCl treatment and DEAE-bagasse in its free base form were most effective in colour removal and the mechanism of colour removal indicated significant contribution of both, the conventional ion exchange and the chemical sorption.     

Progress in the de novo design of structured peptoid protein mimics

Significant progress has been made in recent years toward creating interesting, unique, and in some cases, predictable oligopeptoid/polypeptoid secondary, tertiary, and in one case, quaternary structures. This article describes this progress, identifies a few of the many remaining challenges, and discusses potentially interesting or fruitful strategies for the peptoid biomimetics research community.