Studies on the Mechanism of Action of Miconazole: Effect of Miconazole on Respiration and Cell Permeability of Candida albicans

The antifungal drug, miconazole nitrate, inhibits the growth of several species of Candida. Candida albicans, one of the pathogenic species, was totally inhibited at a concentration of approximately 10 µg/ml. Endogenous respiration was unaffected by the drug at a concentration as high as 100 µg/ml, whereas exogenous respiration was markedly sensitive and inhibited to an extent of 85%. The permeability of the cell membrane was changed as evidenced by the leakage of 260-nm absorbing materials, amino acids, proteins, and inorganic cations. The results we present clearly show that the drug alters the cellular permeability, and thus the exogenous respiration becomes sensitive to the drug.

Supramolecular gels `in action'

n recent years, self-assembly has emerged as a powerful tool for the construction of functional nanostructures. Myriad applications of these nanoscale architectures, especially the supramolecular gels derived from low molecular mass compounds, in fields such as optoelectronics, light harvesting, organic–inorganic hybrid materials, tissue engineering and regenerative medicine are being envisaged. This review attempts to present a succinct overview of the current state of research on functional nano-scale systems—the design, synthesis and applications of self-assembled nanomaterials engineered to carry out precise functions, with an emphasis on supramolecular gel phase materials.

Iterative solution of a class of linear equations with application to reconstruction of three-dimensional object arrays

An iterative algorithm baaed on probabilistic estimation is described for obtaining the minimum-norm solution of a very large, consistent, linear system of equations AX = g where A is an (m times n) matrix with non-negative elements, x and g are respectively (n times 1) and (m times 1) vectors with positive components.

Preparation of 1-acyl-2-succinyl glycero-3-phosphorylcholine and evidence against its involvement in succinate dehydrogenase action

1-Acyl-2-succinyl glycero-3-phosphorylcholine (GPC) was synthesized and its properties described. Although 1-acyl-2-succinyl GPC is a good substrate for succinate dehydrogenase, experiments on the incorporation of [2,3-14C]succinate into mitochondrial lipids gave no evidence to indicate that it is an intermediate in the enzymic oxidation of succinate to fumarate, as has been suggested earlier.

Mode of action of antitumour antibiotics: Spectrophotometric studies on the interaction of chromomycin A3 with DNA and chromatin of normal and neoplastic tissue

The binding of chromomycin A3, an antitumour antibiotic, to various DNA and chromatin isolated from mouse and rat liver, mouse fibrosarcoma and Yoshida ascites sarcoma cells was studied spectrophotometrically at 29°C in 10−2 M Tris-HCl buffer, pH 8.0, containing small amounts of MgCl2 (4.5 · 10−5−25 · 10−5 M). An isobestic point at 415 nm was observed when chromomycin A3 was gradually titrated with Image and its spectrum shifted towards higher wavelength. The rates and extent of these spectral changes were found to be dependent on the concentration of Mg2+. The change in absorbance at 440 nm was used to calculate apparent binding constant (Ka p M−1) and sites per nucleotide (n) from Scatchard plots for various DNA and chromatins. As expected, values of n for chromatin (0.06–0.10) were found to be lower than that found for corresponding DNA (0.10–0.15). Apparently no such correlation exists between binding constants (Ka p M−1 · 10−4) of DNA (6.4–11.2) and of chromatin (3.1–8.3), but Ka p M−1 of chromatin isolated from mouse fibrosarcoma and Yoshida ascites sarcoma are 1.5–3 times higher than that found for mouse and rat liver chromatin. These differences may be taken to indicate structural difference in nucleoprotein complexes caused by neoplasia. The relevance of this finding to tumour suppressive action of chromomycin A3 is discussed.

Dynamics of a class of social interaction systems

A mathematical model of social interaction in the form of two coupler! first-order non-linear differential equations, forms the topic of this study. This non-conservative model io representative of such varied social interaction problems as coexisting sub-populations of two different species, arms race between two rival countries and the like. Differential transformation techniques developed elsewhere in the literature are seen to be effective tools of dynamic analysis of this non-linear non-conservative mode! of social interaction process.

The purification and properties of peroxidase in Mycobacterium tuberculosis H37Rv and its possible role in the mechanism of action of isonicotinic acid hydrazide

Peroxidase from Mycobacterium tuberculosis H37Rv was purified to homogeneity. The homogeneous protein exhibits catalase and Y (Youatt's)-enzyme activities in addition to peroxidase activity. Further confirmation that the three activities are due to a single enzyme was accomplished by other criteria, such as differential thermal inactivation, sensitivity to different inhibitors, and co-purification. The Y enzyme (peroxidase) was separated from NADase (NAD+ glycohydrolase) inhibitor by gel filtration on Sephadex G-200. The molecular weights of peroxidase and NADase inhibitor, as determined by gel filtration, are 240000 and 98000 respectively. The Y enzyme shows two Km values for both isoniazid (isonicotinic acid hydrazide) and NAD at low and high concentrations. Analysis of the data by Hill plots revealed that the enzyme has one binding site at lower substrate concentrations and more than one at higher substrate concentration. The enzyme contains 6g-atoms of iron/mol. Highly purified preparations of peroxidases from different sources catalyse the Y-enzyme reaction, suggesting that the nature of the reaction may be a peroxidatic oxidation of isoniazid. Moreover, the Y-enzyme reaction is enhanced by O2. Isoniazid-resistant mutants do not exhibit Y-enzyme, peroxidase or catalase activities, and do not take up isoniazid. The Y-enzyme reaction is therefore implicated in the uptake of the drug.

Inhibitory action of norepinephrine on the induction of tryptophan-2,3-dioxygenase by cortisol: Mediation by the I-receptor

Induction of hepatic tryptophan-2,3-dioxygenase in rats by cortisol or corticosterone was inhibited on treatment with norepinephrine. The I-adrenergic blockers showed a small potentiating effect of the norepinephrine-mediated inhibition. The I-adrenergic blockers significantly reversed this inhibition, suggesting that norepinephrine acts Image the I-receptor in inhibition of the cortisol-mediated induction of this enzyme.

L_{2}- stability of a class of nonstationary feedback systems with dynamical nonlinear subsystems

A class of feedback systems, consisting of dynamical non-linear subsystems which arise in many diverse control applications, is analyzed for L2-stability. It is shown that, although a transformation of these systems to the familiar Lur'e configuration does not seem to be possible, a one-to-one correspondence may be effected between the stability properties of these and the Lur'e systems. Interesting stability criteria are developed by exploiting this characteristic.

Block- and strand-multiplexing for fast computation of a class of transforms

The transforms dealt with in this paper are defined in terms of the transform kernels which are Kroneeker products of the two or more component kernels. The signal flow-graph for the computation of such a transform is obtained with the flow-graphs for the component transforms as building blocks.

An analytical approach to the study of a class of bi-state social interaction processes

Sufficient conditions for obtaining an equivalent linear model to classes of non-linear, bi-state, social interaction processes are derived. These parametric constraints, when satisfied, permit analytical determination of the dynamics of the non-linear process of social interaction.

A differential transformation technique for the analysis of a class of non-linear time varying systems

The scope of the differential transformation technique, developed earlier for the study of non-linear, time invariant systems, has been extended to the domain of time-varying systems by modifications to the differential transformation laws proposed therein. Equivalence of a class of second-order, non-linear, non-autonomous systems with a linear autonomous model of second order is established through these transformation laws. The feasibility of application of this technique in obtaining the response of such non-linear time-varying systems is discussed.

Mode of Action of a Purified Antitumor Protein from the Proteinaceous Crystal of Bacillus thuringiensis subsp. thuringiensis on Yoshida Ascites Sarcoma Cells

A purified antitumor protein from the proteinaceous crystal of Bacillus thuringiensis subsp. thuringiensis inhibits the growth of Yoshida ascites sarcoma both in vivo and in vitro. Exogenous respiration of the tumor cells was unaffected by the protein at a concentration as high as 500 µg/ml. The antitumor protein inhibits the uptake and incorporation of labeled precursors into macromolecules. However, the ratio of incorporation over uptake is not affected by the protein. Further, the protein brings about the leakage of 260-nm-absorbing material, proteins, and 32P-labeled cellular constituents from the Yoshida ascites sarcoma cells. The results show that the action of the antitumor protein appears to alter the cellular permeability of the tumor cells.

Effect of membrane action on the plastic collapse load of circular orthotropic slabs with fixed edges

In the case of reinforced concrete slabs fixed at the boundaries, considerable enhancement in the load carrying capacity takes place due to compressive membrane action. In this paper a method is presented to analyse the effects of membrane action in fixed orthotropic circular slabs, carrying uniformly distributed loads. Depending on the radial moment capacity being greater or less than the circumferential moment capacity, two cases of orthotropy have been considered. Numerical results are worked out for certain assumed physical parameters and for different coefficients of orthotropy. Variations of load and bending moments with the central deflection are presented.

Site of action of iron in the induction of δ-aminolevulinate dehydratase in Neurospora crassa

δ-Aminolevulinate (ALA) dehydratase, the second and rate limiting enzyme of the heme biosynthetic pathway in the mold Neurospora crassa is induced maximally in 30 min by the addition of iron to iron-deficient cultures. The induction of the enzyme is blocked by cycloheximide, protoporphyrin, 8-azaguanine and cordycepin. Iron also brings about an increase in poly(A)-containing RNA synthesis under conditions of induction. The iron dependent increase in poly(A)-containing RNA synthesis is blocked by protoporphyrin. It is suggested that at the time intervals examined, bulk of the messenger RNA synthesized in response to iron addition represents the messenger for ALA dehydratase.