Journal of Antimicrobial Chemotherapy: optional open access and not-for-profit

All JAC articles are currently freely accessible 12 months after publication, a form of deferred open access. From 2006, JAC will offer the option of author-pays open access, so that individual articles can be made open access immediately upon publication. In addition, JAC will allow the deposition by authors of post-prints of the accepted version of their article as encouraged by granting bodies such as the US National Institutes of Health (NIH), and others. We are adopting such policies to support our authors who must comply with the requirements of their funding bodies and institutions, however, we do not believe that deposition of the post-print form of the article is the most useful step for the progression of research, as we shall note in this article. These changes will enable JAC to deliver the potential for expanded access to articles at a rate determined by the desire among the author community to do so, but without compromising the long-term viability of JAC and the services we offer.     

Single-fiber MHC polymorphic expression is unaffected by sprint cycle training

PURPOSE: The present investigation examined single-fiber MHC alterations in response to high-intensity, short-duration, sprint cycle training. METHODS: Ten untrained college-age male subjects participated in 8 wk of a progressive sprint cycle training program. Training involved 15-s maximal sprints separated by 5 min of rest beginning with four sprints x 2 d in week 1 and increasing to six sprints x 3 d at week 8. Muscle samples from the vastus lateralis were obtained before and after training. A 30-s sprint cycle test was used to evaluate performance before and after training. RESULTS: For the 30-s sprint, mean power and total work increased from pre to post. Single-fiber analyses revealed a reduction in the MHC IIx isoform (2.0 +/- 1.0 to 0.2 +/- 0.1%, pre to post, P < 0.05) and an increase in MHC IIa (P = 0.08), whereas there was no change in hybrid fiber composition (total hybrids = 24%). Generally, MHC IIa content increased and MHC IIx decreased (P < 0.05) as demonstrated by homogenate analyses of tissue samples. CONCLUSIONS: We report that as little as 32 min of high-intensity sprint cycle training over 8 wk is sufficient to improve sprinting performance. This training response is accompanied by an increase in MHC IIa and reduction in MHC IIx content of the vastus lateralis. However, short-duration, high-intensity, sprint cycle training does not cause a reduction in hybrid muscle fiber content.     

Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems

Maillard products arise from condensation reactions between amino acids or proteins with reducing sugars during food processing. As ubiquitous components of human food, these early or advanced glycation products may be subject to intestinal absorption. The present study was performed to investigate the intestinal uptake of Maillard products and to determine whether they are substrates for peptide and amino acid transporters expressed at the apical membrane of Caco-2 cells. At a concentration of 10 mM, N(epsilon)-(carboxymethyl)-L-lysine, N(alpha)-hippuryl-N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine, N(alpha)-hippuryl-N(epsilon)-(carboxymethyl)-L-lysine and N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine inhibited the [(14)C]glycylsarcosine uptake mediated by the H(+)-peptide co-transporter PEPT1 by 13 to 45%. For N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine, an inhibitory constant of 8.7 mM was determined, reflecting a low affinity to PEPT1 in comparison with natural dipeptides. Uptake of L-[(3)H]lysine was weakly affected by N(epsilon)-(carboxymethyl)-L-lysine, N(alpha)-hippuryl-L-lysine and N(alpha)-hippuryl-N(epsilon)-(carboxymethyl)-L-lysine but strongly inhibited by N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine (81%). None of the Maillard products was able to inhibit the uptake of L-[(3)H]leucine by more than 15%. We also studied the transepithelial flux of Maillard products across Caco-2 cell monolayers cultured on permeable filters. The flux rates of Maillard products ranged from 0.01 to 0.3%/cm(2) per h and were shown to be much lower than those of carrier substrates such as glycylsarcosine, L-proline and the space marker [(14)C]mannitol. We conclude that the Maillard products investigated in the present study are neither transported by PEPT1 nor by carriers for neutral amino acids. The low transepithelial flux measured for these compounds most probably occurs by simple diffusion.     

Desmin increases with high-intensity concentric contractions in humans

To investigate the role desmin may play in muscular adaptation to exercise, we measured desmin protein content in the vastus lateralis muscle of seven untrained men in response to 8 weeks of high-intensity cycle training. Training involved 15-s sprints separated by rest for 5 min. Subjects began with four sprints twice per week, and progressed to six sprints three times per week. Peak power was measured before and after training with a 30-s maximal sprint test. Mean power during the first 15 s increased significantly after training (P < 0.05). Desmin and actin protein levels were determined by immunoblotting, from pretraining and posttraining muscle biopsies. Desmin protein levels were increased by 60% after training (P < 0.01), whereas actin protein levels did not change with training. We conclude that the cytoskeletal protein desmin increases in response to a high-tension, concentric-only load consequent to sprint training. Desmin appears to increase as the force generating capacity of the muscle increases. A reinforced desmin cytoskeleton may be necessary for increased force generation by the muscle.     

DNA identification of fetal cells isolated from cervical mucus: potential for early non-invasive prenatal diagnosis

OBJECTIVES: To develop a reliable method to isolate fetal cells for genetic diagnosis. DESIGN: Aspiration of cervical mucus from pregnant women in the first trimester. SETTING: Pregnant women were recruited before an elective termination of pregnancy. POPULATION: Sixty pregnant women (7-10 weeks of gestation). METHODS: Fetal cells were isolated from aspirated cervical mucus of pregnant women using a combination of enzymatic digestion, fluorescent immunohistochemistry, micromanipulation and single-cell DNA allelic profiling. MAIN OUTCOME MEASURES: The isolation and identification of fetal cells. RESULTS: The transformation of the tenacious cervical mucus into a single-cell suspension enabled the isolation and identification of fetal cells by fluorescent immunohistochemistry. Confirmation of fetal origin was accomplished by single-cell DNA allelic profiling alongside known maternal cells. CONCLUSIONS: This novel non-invasive method is rapid and efficient with results attainable within 24 hours as early as seven weeks of gestation. The technique would offer earlier reassurance and the option of first trimester therapeutic abortions to both high and low risk pregnant women.     

Tumor-specific intravenous gene delivery using oncolytic adenoviruses

In this report, we describe a vector system that specifically delivers transgene products to tumors following intravenous (i.v.) administration. The Escherichia coli cytosine deaminase (CD) gene was placed in the E3B region of the tumor-selective, replication-competent adenovirus ONYX-411, under the control of endogenous viral late gene regulatory elements. Thus, CD expression was directly coupled to the tumor-selective replication of the viral vector. In vitro, CD was expressed efficiently in various human cancer cell lines tested but not in cultured normal human cells, including human hepatocytes. Following i.v. administration into nude mice carrying human tumor xenografts, robust CD activity was detected only in tumors but not in liver or other normal tissues. Levels of CD activity in the tumors increased progressively following i.v. virus administration, correlating closely with virus replication in vivo. Subsequent administration of 5-fluorocytosine (5-FC) demonstrated a trend to improve the antitumor efficacy of these viruses in a mouse xenograft model, presumably due to the intratumoral conversion of 5-FC to the chemotherapeutic drug 5-fluorouracil. We show that the combination of a highly selective oncolytic virus, ONYX-411, with the strategic use of the viral E3B region for transgene insertion provides a powerful platform that allows for tumor-specific, persistent and robust transgene expression after i.v. administration. This technology provides an opportunity to enhance greatly both safety and efficacy of cancer gene therapy.     

Evidence-based consumer choice: a case study in colorectal cancer screening

OBJECTIVES: To elicit community preferences for colorectal cancer (CRC) screening by faecal occult blood test (FOBT) using discrete choice modeling (DCM). To provide policymakers with information that would assist them in designing the future national screening program. METHODS: 301 participants in central Sydney, aged 50 to 70 years, at 'average' risk of CRC, participated in a face-to-face discrete choice study interview in which screening profiles were posed to derive estimates for preferences for CRC FOBT screening. RESULTS: Three characteristics were varied in our screening profiles, namely: benefit (CRC deaths prevented); potential harm (false positive induced colonoscopy); and notification policy (of test result). Ninety-four respondents (32%) did not trade off CRC deaths prevented for any reduction in harms. Twelve per cent always chose no screening. The remaining 56% traded benefits and harms. These latter respondents (n = 164) were willing to accept 853 (false positive induced) colonoscopies for one CRC death prevented. CONCLUSIONS: While survival was all that mattered for just over one-third of the sample and 12% would choose no screening, the remaining individuals were prepared to trade CRC deaths prevented against other characteristics. CRC screening will not receive unqualified community support, irrespective of harms. IMPLICATIONS: In any future national CRC screening program, consideration of these insights about community assessment of benefits, harms, costs and other characteristics of CRC screening is warranted.