Antitubercular activity of lomefloxacin in an experiment

The effect of lomefloxacin was studied on mice with experimental infection due to Mycobacterium tuberculosis. The antibiotic was administered in doses of 100 and 200 mg/kg. It was shown that the use of lomefloxacin for a month provided a lower death rate of the animals with progressing acute generalized tuberculosis, a lower level of the lesions in the internal organs and a lower number of the Mycobacterium isolates from them. The efficacy of the treatment depended on the drug dose. When lomefloxacin was used in a dose of 200 mg/kg, the survival rate was much higher and the number of the epithelial unicellular granulomas in the tissue of the lung and spleen was markedly decreased while with the lower dose the indices did not differ from those in the control.     

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Fixed-order H∞ compensator design

A method is presented for the construction of fixed-order compensators to provide H_∞ norm constraint for linear control systems with exogenous disturbances. The method is based on the celebrated bounded-real lemma that predicates the H_∞ norm constraint via a Riccati inequality. The synthesis of fixed-order controllers whose dimensions are less than the order of a given plant, is demonstrated by a set of sufficient conditions along with a numerical algorithm.     

Sheldon H. White (1928-2005).

Sheldon "Shep" Harold White, one of developmental psychology's most distinguished scholars, died on March 17, 2005, at the age of 76. He is perhaps best remembered for his sharp intellect, generous spirit, good humor, and warm compassion. Shep's principal work lay in three intermeshed areas: children's learning and cognitive development, social programs and policies, and the history of developmental psychology. Shep White is sorely missed by his family and friends, and countless children have unknowingly benefited from his research, scholarship, and contributions to public policy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the determination of boundaries to manipulator workspaces

The accumulation of two independent, broadly applicable formulations for determining the boundary to manipulator workspaces, presented elsewhere, are compared in this paper. Insights gained from one method are used to explain behavior exhibited in the other. Results are also compared and validated. A numerical formulation based on continuation methods is used to map curves that are on the boundary of a manipulator workspace. Analytical criteria based on row rank deficiency criteria of the manipulator's analytical Jacobian are used to map a family of one-dimensional solution curves on the boundary. The other formulation, based on a similar rank-deficiency criteria, yields analytic boundaries parametrized in terms of surface patches on the boundary. Results concerning the applicability of the numerical method to open- and closed-loop systems are compared with those limited to the open-loop for the analytical method. Conclusions regarding the behavior of the manipulator on geometric entities characterized by singular curves, higher-order bifurcation points, and surfaces inside the workspace are drawn. Applicability of both methods and their limitations are also addressed.     

Top-down logic design with pass-transistor cells and efficientsynthesiser

A pass-transistor based cell library containing only two types of cells is designed and a corresponding logic/circuit synthesiser developed for logic mapping of any combinational circuit. The proposed design has better performance than the recently proposed lean integration with pass transistors (LEAP) cell library. Furthermore, the modified LEAP cell library can be easily migrated to a new process technology due to the smaller number of cells     

Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia

F2-isoprostanes are bioactive prostaglandin (PG)-like compounds that are produced from arachidonic acid through a nonenzymatic process of lipid peroxidation catalyzed by oxygen free-radicals. 8-Epi-PGF2 alpha may amplify the platelet response to agonists, circulates in plasma, and is excreted in urine. We examined the hypothesis that the formation of 8-epi-PGF2 alpha is altered in patients with hypercholesterolemia and contributes to platelet activation in this setting. Urine samples were obtained from 40 hypercholesterolemic patients and 40 age- and sex-matched control subjects for measurement of immunoreactive 8-epi-PGF2 alpha. Urinary excretion of 11-dehydro-thromboxane (TX) B2, a major metabolite of TXA2, was measured as an in vivo index of platelet activation. Low-dose aspirin, indobufen, and vitamin E were used to investigate the mechanism of formation and effects of 8-epi-PGF2 alpha on platelet activation. Urinary 8-epi-PGF2 alpha was significantly (P = .0001) higher in hypercholesterolemic patients than in control subjects: 473 +/- 305 versus 205 +/- 95 pg/mg creatinine. Its rate of excretion was inversely related to the vitamin E content of LDL and showed a positive correlation with urinary 11-dehydro-TXB2. Urinary 8-epi-PGF2 alpha was unchanged after 2-week dosing with aspirin and indobufen despite complete suppression of TX metabolite excretion. Vitamin E supplementation was associated with dose-dependent reductions in both urinary 8-epi-PGF2 alpha and 11-dehydro-TXB2 by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively. We conclude that the in vivo formation of the F2-isoprostane 8-epi-PGF2 alpha is enhanced in the vast majority of patients with hypercholesterolemia. This provides an aspirin-insensitive mechanism possibly linking lipid peroxidation to amplification of platelet activation in the setting of hypercholesterolemia. Dose-dependent suppression of enhanced 8-epi-PGF2 alpha formation by vitamin E supplementation may contribute to the beneficial effects of antioxidant treatment.