Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.     

A cost comparison of balloon angioplasty and stenting versus endarterectomy for the treatment of carotid artery stenosis

PURPOSE: Percutaneous transluminal angioplasty with stenting (PTAS) of the carotid artery has been advocated as an alternative treatment for high-grade stenosis. Rationale for this approach includes less morbidity, shorter recovery, and lower cost when compared with carotid endarterectomy (CEA). METHODS: The clinical results and hospital charges of patients who underwent elective treatment for carotid stenosis were reviewed. During a concurrent 14-month period, 218 patients were admitted 229 times for 234 procedures for the treatment of 239 carotid bifurcation stenoses, 109 by PTAS and 130 by CEA. Hospital charges were reviewed for each hospitalization and were categorized according to radiology, operating room, cardiac catheterization laboratory, and all other hospital charges. RESULTS: The combined incidence of postprocedure strokes and deaths were: PTAS, eight strokes (7.7%) and one death (0.9%); CEA, two strokes (1.5%) and two deaths (1.5%). Total hospital charges per admission for the two groups were $30,140 for PTAS and $21,670 for CEA. The average postprocedure length of stay for PTAS was 2.9 days (median, 2 days) and for CEA was 3.1 days (median, 3 days). Cardiac catheterization laboratory charges for the PTAS group were $12,968, whereas the operating room charges for the CEA group were $4263. When hospitalizations that were extended by complications were excluded, the average total charges for the PTAS group (n = 84) dropped to $24,848 (mean length of stay, 1.9 days) and for the CEA group (n = 111) to $19,247 (mean length of stay, 2.6 days). CONCLUSIONS: After evaluating hospital charges, PTAS for the treatment of carotid stenosis cannot currently be justified on the basis of reduced costs alone. With future cost-containing measures, total hospital charges can be reduced in both groups.     

36%渗乐乳油

３６％渗乐乳油田ＨＰ－１增效剂与乐果及其他助剂调配而成。五年田间小区和大田药效试验证明：３６％渗乐乳油高效，安全，用量少，对各类蚜虫防效优异。     

Hemodynamic effects of spinal anesthesia in the elderly: single dose versus titration through a catheter

Protective immunity against infection with Mycobacterium tuberculosis is imparted by T cells rather than antibodies, but B cells can play a role as antigen-presenting cells and in granuloma formation. We re-evaluated the role of B cells in the course of tuberculous infection in mu-chain knock-out (Ig-) mice. Surprisingly, the organs of M. tuberculosis-infected Ig- mice were found to have three- to eight-fold elevated counts of viable bacilli compared with normal littermates at 3-6 weeks post-infection. Splenic interferon-gamma responses to whole antigen were unimpaired, whilst proliferation to certain mycobacterial peptides was found to be diminished. However, bacille Calmette-Guérin (BCG) vaccination significantly reduced the infection in Ig- mice. The mechanisms by which B cells can influence primary tuberculous infection need further study.     

Gastrointestinal problems in diabetes

Gastrointestinal symptoms are often encountered in patients with diabetes mellitus. Symptoms may arise in any region of the alimentary tract; common symptoms are heartburn, nausea, vomiting, diarrhea, constipation, fecal incontinence, and abdominal pain. This article reviews practical approaches to the identification of the pathophysiologic mechanisms involved in diabetic enteropathies and their complications and briefly outlines strategies to treat these symptoms. Particular emphasis is placed on applied physiologic tests and the choice of pharmacotherapy (e.g., cisapride, erythromycin, or octeotide). The current role of pancreatic transplantations also is briefly reviewed.     

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.     

Drift hole mobility in strained and unstrained doped Si1-xGex alloys

Results of the drift hole mobility in strained and unstrained SiGe alloys are reported for Ge fractions varying from 0 to 30% and doping levels of 10¹⁵-10¹⁹ cm^-3. The mobilities are calculated taking into account acoustic, optical, alloy, and ionized-impurity scattering. The mobilities are then compared with experimental results for a boron doping concentration of 2×10¹⁹ cm^-3. Good agreement between experimental and theoretical values is obtained. The results show an increase in the mobility relative to that of silicon     

Efficient diode-pumped single-frequency erbium:ytterbium fiberlaser

We report a 7.6-mW single-frequency fiber laser operating at 1545 nm, using for the first time an Er³⁺:Yb³⁺ doped fiber and a fiber grating output coupler. The laser did not exhibit self-pulsation, which is a typical problem in short three-level fiber lasers, and had a relative intensity noise (RIN) level below -145.5 dB/Hz at frequencies above 10 MHz. The linewidth of the laser was limited by the relaxation oscillation sidebands in the optical spectrum and was typically less than 1 MHz