Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

The effects of cholecystokinin A and B receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in rat

The present study has been divided into two sets. In the first set, the aim of the experiments was to investigate the dose-response effect of selective serotonin re-uptake inhibitor (SSRI) citalopram on rat exploratory behaviour in the elevated plus-maze. In the second set of experiments, the effect of cholecystokinin (CCK) CCKA and CCKB receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in the elevated plus-maze was studied. Citalopram (5 and 10 mg/kg) decreased the number of open and total arm entries, line crossings on open arms, and percentage of time spent exploring in open arm. Dose 15 mg/kg was without any effect on rat exploratory behaviour. Devazepide (0.01 and 1.0 mg/kg) failed to modify any of the citalopram-induced changes observed. L 365260 (1.0 mg/kg) reversed most of the effects of citalopram: the numbers of open and total arm entries, the number of line crossings, and the percentage of time spent exploring in open arms. L 365260 at dose level 0.01 mg/kg was ineffective. These results support the involvement of the CCKB receptor subtype in SSRI-induced anxiogenic-like effects in rodents.     

Impact of crosstalk in an arrayed-waveguide multiplexer onN×N optical interconnection

The impact of crosstalk in an arrayed-waveguide N×N wavelength multiplexer is investigated precisely in relation to its application to wavelength-routing N×N all optical networks. In such systems multiple crosstalk light which has the same wavelength as the signal results in signal-crosstalk beat noise. We confirm that the noise is Gaussian and obtain the relation between crosstalk and power penalty. It is shown that the crosstalk must be less than -38 dB for a 16×16 system to keep the power penalty below 1 dB at a bit error rate of 10^-9     

Complications of chronic otitis media

In summary, recent literature indicates that the complications of chronic otitis media have been decreasing. However, even with the advent of modern and more powerful antimicrobials and aggressive surgical eradication of disease, the morbidity and mortality are still high. Some complications may initially be quite obvious and some complications may be quite subtle. Therefore, the most important tools in making early diagnosis are careful history and physical examination, and a high index of suspicion for impending complications.     

Two methods of determining the ultimate long-term shear strength of clayey soils

A comparison is made between different alternate schemes for determination of the strength of soils possessing rheological properties on the basis of our own experimental data. An original method is proposed for determination of the ultimate long-term strength from tests on the conditionally instantaneous failure of soil after preliminary deformation in a creep regime, as well as from tests in a controlled-deformation regime. Translated from Osnovaniya, Fundamenty i Mekhanika Gruntov, No. 1, pp. 14–18, January–February, 1996.     

A medium-access control protocol for a cellular packet CDMAcarrying multirate traffic

We propose and evaluate a medium-access control (MAC) protocol for synchronous cellular packet direct-sequence code-division multiple-access (DS/CDMA). The protocol is designed for handling a variety of multimedia traffic types in an integrated wireless-access network (IWAN). For instance, the protocol is suited for carrying multiple traffic types of different priorities. An analytical model for the equilibrium state has been developed for the proposed protocol. A comparative evaluation of the protocol is done for three different radio frequency bandwidths currently under consideration for personal communication services (PCS), i.e., 1.25 MHz, 5 MHz, and 10 MHz. Our results demonstrate that the proposed protocol is both robust and flexible for the intended IWAN applications. It offers a significant multiplexing gain as the bandwidth increases     

Morphological changes induced by colchicine in the chick optic cup in early stages of development. A stereological study

In this study chick embryo optic cups at HH stage 13 of development were analyzed under normal conditions and after inoculation with colchicine for 1, 2, 4, and 8 h. Several changes were seen after these periods of treatment: 1) modifications of the structure, with thicker regions in the cup and a general decrease in the total volume according to the duration of exposure to the drug (about 4 times less than normal, 5,035 x 10(3) microns 3 vs 1,334 x 10(3) microns 3 after 8 h of treatment); 2) enlargement of the ventricular cavity and its closure, due to failure of approximation of retinal and pigmentary layers; 3) failure of lens development, with delay and impairment of pit formation and deformation of all structures; lens volume was less than normal (about 4 times less, 2,148 x 10(3) microns 3 vs 658 x 10(3) microns 3 after 8 h of treatment); 4) a general segregation of the cells making up the structure, principally in the more active proliferating zones. The local alterations found are described.     

Radiation therapy of giant aggressive keratoacanthomas

BACKGROUND AND DESIGN: Giant aggressive keratoacanthoma is a rare destructive subset of keratoacanthoma that frequently involves the facial region, grows rapidly to a large size, and often recurs after surgical management. The effectiveness of ionizing radiation therapy was examined in a retrospective study involving 16 patients; 14 of the tumors had recurred after surgical therapy. RESULTS: All tumors resolved with satisfactory cosmetic results and without recurrence following a fractionated course of superficial radiation therapy. CONCLUSIONS: Radiation therapy is an effective therapeutic modality for giant aggressive keratoacanthomas.     

Sociopolitical effects on personality research.

Comments on L. R. Goldberg's (see record 1993-17546-001) history of the Big Five framework of personality traits and elaborated on its use. The reasons why industrial/organizational psychologists de-emphaszied the impact of personality on the job peformance in the late 1960s and 1970s and re-emphasized it in the 1980s are addressed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)