Feasibility and Efficacy of a Brief Mindfulness-Based Smoking Intervention Delivered via the Internet: A Randomized Controlled Trial.

Background: A growing body of literature suggests that mindfulness-based interventions are effective in reducing smoking. However, existing mindfulness interventions are often lengthy and require extensive interaction with a therapist, making them inaccessible to a large percentage of the population. The current study addressed this issue by testing the feasibility and efficacy of a single session, web-based, mindfulness intervention for smoking cessation. Methods: Participants (N = 80) took part in a fully online cue exposure exercise interspersed with brief instructions on how to cope with cravings for cigarettes. All participants were randomly assigned to receive either mindfulness-based or coping as usual instructions. Outcomes included participant satisfaction with the intervention, self-reported craving following the cue exposure exercise, and cigarette use 30 days post-intervention. Results: Participants in both groups found the instructions moderately helpful and easy to understand. Participants in the mindfulness group reported a significantly smaller increase in craving than those in the control group following the cue exposure exercise. Averaging across conditions, participants reported smoking fewer cigarettes in the 30 days following the intervention than in the 30 days prior, however there were no between group differences in cigarette use. Conclusion: Mindfulness-based interventions for smoking reduction can be effectively implemented in a brief, single-session online format. These interventions are easy to disseminate and can reach a large number of smokers with minimal participant burden. Results from the current study suggest that mindfulness-based interventions can help participants control craving in the face of smoking-related cues, although perhaps not change smoking quantity. Future research is needed to explore factors which may increase the efficacy of online, mindfulness-based interventions for smoking cessation, while still maintaining their accessibility and reach.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

BACKGROUND: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. METHODS: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease-free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. RESULTS: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p = 0.394). Median post-recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p = 0.031). Median OS reached 33.2 versus 25.2 months (p = 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favoured GPH (p = 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. CONCLUSIONS: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. CLINICALTRIALS: gov, number NCT01077427.

Self-Disinfecting Copper Beds Sustain Terminal Cleaning and Disinfection Effects throughout Patient Care.

Microbial burden associated with near-patient touch surfaces results in a greater risk of health care-associated infections (HAIs). Acute care beds may be a critical fomite, as traditional plastic surfaces harbor the highest concentrations of bacteria associated with high-touch surfaces in a hospital room's patient zone. Five high-touch intensive care unit (ICU) bed surfaces encountered by patients, health care workers, and visitors were monitored by routine culture to assess the effect U.S. Environmental Protection Agency (U.S. EPA)-registered antimicrobial copper materials have on the microbial burden. Despite both daily and discharge cleaning and disinfection, each control bed's plastic surfaces exceeded bacterial concentrations recommended subsequent to terminal cleaning and disinfection (TC&D) of 2.5 aerobic CFU/cm2 Beds with self-disinfecting (copper) surfaces harbored significantly fewer bacteria throughout the patient stay than control beds, at levels below those considered to increase the likelihood of HAIs. With adherence to routine daily and terminal cleaning regimes throughout the study, the copper alloy surfaces neither tarnished nor required additional cleaning or special maintenance. Beds encapsulated with U.S. EPA-registered antimicrobial copper materials were found to sustain the microbial burden below the TC&D risk threshold levels throughout the patient stay, suggesting that outfitting acute care beds with such materials may be an important supplement to controlling the concentration of infectious agents and thereby potentially reducing the overall HAI risk.IMPORTANCE Despite cleaning efforts of environmental service teams and substantial compliance with hand hygiene best practices, the microbial burden in patient care settings often exceeds concentrations at which transfer to patients represents a substantial acquisition risk for health care-associated infections (HAIs). Approaches to limit HAI risk have relied on designing health care equipment and furnishings that are easier to clean and/or the use of no-touch disinfection interventions such as germicidal UV irradiation or vapor deposition of hydrogen peroxide. In a clinical trial evaluating the largest fomite in the patient care setting, the bed, a bed was encapsulated with continuously disinfecting antimicrobial copper surfaces, which reduced the bacteria on surfaces by 94% and sustained the microbial burden below the terminal cleaning and disinfection risk threshold throughout the patient's stay. Such an intervention, which continuously limits microbes on high-touch surfaces, should be studied in a broader range of health care settings to determine its potential long-range efficacy for reducing HAI.

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial.

IMPORTANCE: Patients with soft tissue sarcoma are at risk for local recurrence and distant metastases despite optimal local treatment. Preoperative anthracycline plus ifosfamide chemotherapy improves outcome in common histological subtypes. OBJECTIVE: To analyze whether the previously reported improvement in local progression-free survival by adding regional hyperthermia to neoadjuvant chemotherapy translates into improved survival. DESIGN, SETTING, AND PARTICIPANTS: Open-label, phase 3 randomized clinical trial to evaluate the efficacy and toxic effects of neoadjuvant chemotherapy plus regional hyperthermia. Adult patients (age ≥18 years) with localized soft tissue sarcoma (tumor ≥5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep) were accrued across 9 centers (6, Germany; 1, Norway; 1, Austria; 1, United States) from July 1997 to November 2006. Follow-up ended December 2014. INTERVENTIONS: After stratification for tumor presentation and site, patients were randomly assigned to either neoadjuvant chemotherapy consisting of doxorubicin, ifosfamide, and etoposide alone, or combined with regional hyperthermia. MAIN OUTCOMES AND MEASURES: The primary end point was local progression-free survival. Secondary end points included treatment safety and survival, with survival defined from date of randomization to death due to disease or treatment. Patients lost to follow-up were censored at the date of their last follow-up. RESULTS: A total of 341 patients were randomized, and 329 (median [range] age, 51 [18-70] years; 147 women, 182 men) were eligible for the intention-to-treat analysis. By December 2014, 220 patients (67%; 95% CI, 62%-72%) had experienced disease relapse, and 188 (57%; 95% CI, 52%-62%) had died. Median follow-up was 11.3 years. Compared with neoadjuvant chemotherapy alone, adding regional hyperthermia improved local progression-free survival (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P = .002). Patients randomized to chemotherapy plus hyperthermia had prolonged survival rates compared with those randomized to neoadjuvant chemotherapy alone (HR, 0.73; 95% CI, 0.54-0.98; P = .04) with 5-year survival of 62.7% (95% CI, 55.2%-70.1%) vs 51.3% (95% CI, 43.7%-59.0%), respectively, and 10-year survival of 52.6% (95% CI, 44.7%-60.6%) vs 42.7% (95% CI, 35.0%-50.4%). CONCLUSIONS AND RELEVANCE: Among patients with localized high-risk soft tissue sarcoma the addition of regional hyperthermia to neoadjuvant chemotherapy resulted in increased survival, as well as local progression-free survival. For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003052.

Antibacterial Diamines Targeting Bacterial Membranes.

Antibiotic resistance is a growing threat to human health exacerbated by a lack of new antibiotics. We now describe a series of substituted diamines that produce rapid bactericidal activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus and stationary-phase bacteria. These compounds reduce biofilm formation and promote biofilm dispersal in Pseudomonas aeruginosa. The most potent analogue, 3 (1,13-bis{[(2,2-diphenyl)-1-ethyl]thioureido}-4,10-diazatridecane), primarily acts by depolarization of the cytoplasmic membrane and permeabilization of the bacterial outer membrane. Transmission electron microscopy confirmed that 3 disrupts membrane integrity rapidly. Compound 3 is also synergistic with kanamycin, demonstrated by the checkerboard method and by time-kill kinetic experiments. In human cell toxicity assays, 3 showed limited adverse effects against the HEK293T human kidney embryonic cells and A549 human adenocarcinoma cells. In addition, 3 produced no adverse effects on Caenorhabditis elegans development, survival, and reproduction. Collectively, diamines related to 3 represent a new class of broad-spectrum antibacterials against drug-resistant pathogens.

Exploring naturally occurring ivy nanoparticles as an alternative biomaterial.

Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates of Hedera helix (English ivy), have shown promising potential to be used in nanomedicine owing to their excellent aqueous solubility, low intrinsic viscosity, biocompatibility, and biodegradability. In this study, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine are evaluated. Via electrostatic and hydrophobic interactions, pH-responsive nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an entrapment ratio of 77.9±3.9%. While the INPs show minimal cytotoxicity, the formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than free DOX against multiple cancer cell lines, suggesting a synergistic effect is established upon conjugation. The anti-cancer effects of the INP-DOX conjugates are further evaluated via in vivo xenograft assays by subcutaneously implanting DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice treated with the INP-DOX conjugates are significantly less than those of the mice treated with free DOX. In addition, the INPs are further exploited as nano-fillers to develop fibrous scaffolds with collagen, via mimicking the porous matrix where the INPs are embedded under natural condition. Enhanced adhesion of smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are observed in this newly constructed scaffold. Overall, the results obtained from the present study suggest great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein architecture that is amenable for modification according to the functional designs, capable of being developed as versatile nanomaterials for extensive biomedical applications. STATEMENT OF SIGNIFICANCE: Naturally occurring organic nanomaterials have drawn increasing interest for their potential biomedical applications in recent years. In this study, a new type of naturally occurring nanoparticles obtained from the sticky exudates on the adventitious roots of English ivy (H. helix), was explored for its potential biomedical application. In particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine were evaluated both in vitro and in vivo. Overall, the results obtained from the present study suggest the great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. This study may open a totally new frontier for exploring the biomedical application of naturally occurring nanomaterials.

Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study.

OBJECTIVE: To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas. BACKGROUND: Within the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections. METHODS: A subgroup analysis of the EORTC trial was performed and long-term survival determined. From 341 patients, 149 (median age 52 years, 18-69) were identified with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six patients were treated with EIA (etoposide, ifosfamide, doxorubicin)+RHT (≥5 cycles: 69.7%) versus 73 patients receiving EIA alone (≥5 cycles: 52.1%, P=0.027). LPFS and DFS as well as overall survival were determined. RESULTS: RHT and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years, P=0.044) and DFS (34% vs 27% after 5 years, P=0.040). Overall survival was not significantly improved in the RHT group (57% vs 55% after 5 years, P=0.82). Perioperative morbidity and mortality were not significantly different between groups. CONCLUSIONS: In patients with macroscopically complete tumor resection, RHT in addition to chemotherapy resulted in significantly improved local tumor control and DFS without increasing surgical complications. Within a multimodal therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is a treatment option beside radical surgery and should be further evaluated in future trials.

Feeding of the probiotic bacterium Enterococcus faecium NCIMB 10415 differentially affects shedding of enteric viruses in pigs.

Effects of probiotic bacteria on viral infections have been described previously. Here, two groups of sows and their piglets were fed with or without feed supplementation of the probiotic bacterium Enterococcus faecium NCIMB 10415. Shedding of enteric viruses naturally occurring in these pigs was analyzed by quantitative real-time RT-PCR. No differences between the groups were recorded for hepatitis E virus, encephalomyocarditis virus and norovirus. In contrast, astrovirus was exclusively detected in the non-supplemented control group. Rotavirus was shedded later and with lower amounts in the probiotic piglet group (p < 0.05); rotavirus-shedding piglets gained less weight than non-infected animals (p < 0.05). Serum titres of anti-rotavirus IgA and IgG antibodies were higher in piglets from the control group, whereas no difference was detected between sow groups. Phenotype analysis of immune cell antigens revealed significant differences of the CD4 and CD8ß (p < 0.05) as well as CD8α and CD25 (p < 0.1) T cell populations of the probiotic supplemented group compared to the non-supplemented control group. In addition, differences were evident for CD21/MHCII-positive (p < 0.05) and IgM-positive (p < 0.1) B cell populations. The results indicate that probiotic bacteria could have effects on virus shedding in naturally infected pigs, which depend on the virus type. These effects seem to be caused by immunological changes; however, the distinct mechanism of action remains to be elucidated.

Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation.

Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type (WT) and UCP2 knockout (KO) mice and subjected them to hypoxia/reoxygenation (H/R). Using cultured hepatocytes treated with emulsified fatty acids for 24 h, generating a steatotic phenotype (i.e., microvesicular and broad-spectrum fatty acid accumulation), we found that the phenotype of the WT and UCP2 KO were the same; however, cellular viability was increased in the steatotic KO hepatocytes following 4 h of hypoxia and 24 h of reoxygenation; Hepatocellular ATP levels decreased during hypoxia and recovered after reoxygenation in the control and UCP2 KO steatotic hepatocytes but not in the WT steatotic hepatocytes; mitochondrial membrane potential in WT and UCP2 KO steatotic groups was less than control groups but higher than UCP2 KO hepatocytes. Following reoxygenation, lipid peroxidation, as measured by thiobarbituric acid reactive substances, increased in all groups but to a greater extent in the steatotic hepatocytes, regardless of UCP2 expression. These results demonstrate that UCP2 sensitizes steatotic hepatocytes to H/R through mitochondrial depolarization and ATP depletion but not lipid peroxidation.

High-dose intra-arterial verapamil for the treatment of cerebral vasospasm after subarachnoid hemorrhage: prolonged effects on hemodynamic parameters and brain metabolism.

BACKGROUND: Studies attempting to establish the safety and efficacy of standard and high-dose intra-arterial infusions of calcium channel blockers for treatment of cerebral vasospasm have focused on hemodynamic changes during the angiographic procedure. OBJECTIVE: To evaluate longer-term drug effects over the hours following infusion and the effects on brain tissue oxygen tension or cerebral metabolism. METHODS: We studied 11 patients with poor-grade aneurysmal subarachnoid hemorrhages who underwent multimodality brain monitoring and angiography with infusion of high-dose intra-arterial verapamil (≥15 mg total dose). Hourly intracerebral microdialysis measurements and continuously recorded mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbto2 were analyzed for 6 hours before and 12 hours following treatment. RESULTS: A median dose of 23 mg (range, 15-55 mg) of intra-arterial verapamil was given. Compared with baseline values, reductions in CPP and MAP were maximal at 3 hours postangiography (from 105 ± 13 mm Hg to 95 ± 15 mm Hg and from 116 ± 12 mm Hg to 106 ± 16 mm Hg, P < .01) and persisted for up to 6 hours (P < .04); increases in vasopressor therapy were required in 8 procedures (53%). ICP significantly increased during the first 3 hours post angiography (P < .03). Brain glucose increased by 33% by hour 9 (P < .001). There were no significant changes in Pbto2 or the lactate/pyruvate ratio. CONCLUSION: High-dose intra-arterial verapamil causes increases in ICP and reductions in CPP, followed by an increase in brain glucose levels, without altering brain oxygen tension or oxidative metabolism. Patients undergoing high-dose intra-arterial verapamil therapy warrant close hemodynamic and ICP monitoring for at least 12 hours following treatment.

Preserved flow-mediated dilation in adults with cyanotic congenital heart disease.

Adults with cyanotic congenital heart disease (CCHD) have been shown to have endothelial dysfunction in the forearm resistance vessels as assessed with venous occlusion plethysmography. Whether these abnormalities are confined to the microvasculature or reflect generalized endothelial dysfunction remain unknown. We used high-resolution ultrasound to compare flow responses and endothelial-dependent flow-mediated dilation (FMD) in the brachial artery of 13 adult patients with CCHD and 14 healthy controls. High-dose vitamin C was infused to evaluate the possible role of reactive oxygen species on endothelial vasomotor function. FMD was measured both prior to and after vitamin C infusion. Sublingual glyceryl nitrate was given to assess endothelium-independent responses. FMD did not differ among patients with CCHD and controls either before (6.2 +/- 4.1, 5.1 +/- 2.6%, p = 0.44) or after (5.1 +/- 2.8, 5.2 +/- 3.1%, p = 0.90) vitamin C infusion. Endothelium-independent vasodilatation was similar in both groups (14.3 +/- 3.7, 13.2 +/- 4.4%). There were no differences in baseline flow or in measures of reactive hyperemia. Adults with CCHD appear to have preserved endothelial function in their conduit arteries. This suggests that these patients are not at an increased risk of premature atherosclerotic cardiovascular events.

Breathing and voice quality after surgical treatment for bilateral vocal cord paralysis.

OBJECTIVE: To evaluate long-term results of surgical treatment for bilateral vocal cord paralysis using objective and subjective measures of breathing and voice quality. DESIGN: Prospective cross-sectional case series. SETTING: Tertiary care otolaryngology and speech pathology referral center. PATIENTS: Ten patients with bilateral vocal cord paralysis who underwent surgical treatment between October 1996 and May 2006 at the Department of Otorhinolaryngology-Head and Neck Surgery, University of Würzburg, were examined at a mean of 27.2 months after surgery. MAIN OUTCOME MEASURES: Glottal area, voice range profile, Voice Handicap Index, pulmonary function test results, Göttingen Hoarseness Diagram, microlaryngostroboscopic findings, chronic respiratory disease questionnaire, and European Organization for Research and the Treatment of Cancer quality-of-life questionnaire, including the head and neck module. RESULTS: Residual recurrent nerve function was seen in 9 of 10 patients. Pulmonary data varied widely and did not correlate with the size of the glottal area. Quality of life, subjective dyspnea, and physical functioning correlated with expiratory airflow measures. Voice range was reduced in all patients. High breathiness and reduced maximum phonation time led to increased Voice Handicap Index scores. CONCLUSIONS: Microlaryngostroboscopic findings did not necessarily correlate with subjective dyspnea and vocal complaints. Reduction of inspiratory speaking efforts and acquisition of special breathing techniques improve airflow stability and effectiveness of respiration, leading to enhanced quality of life.

Impact of the probiotic bacteria Enterococcus faecium NCIMB 10415 (SF68) and Bacillus cereus var. toyoi NCIMB 40112 on the development of serum IgG and faecal IgA of sows and their piglets.

To examine the influence of two different probiotic bacteria on the humoral immune system of swine, two animal studies were carried out with sows and their litters. The sows' feed was supplemented with either Enterococcusfaecium NCIMB 10415 (SF68) or Bacillus cereus var. toyoi NCIMB 40112 beginning early in pregnancy. The total IgA content in the faeces as well as the total IgG concentration in the blood of the sows was recorded before and after weaning. The same parameters were determined in the blood and faeces of the piglets. In sows, only feed supplementation with B. cereus led to a clear increase in faecal IgA. Serum IgG levels were not significantly affected by any probiotic feeding in sows. In piglets, the group that was fed B. cereus showed significantly higher faecal IgA levels shortly before weaning, whereas in the E. faecium group, a significant decrease in IgA levels was observed one week after weaning. In both probiotic fed groups the post-weaning IgG levels were significantly decreased compared to the respective control groups. We conclude that B. cereus var. toyoi feed supplementation led to an increased intestinal IgA secretion both in sows and piglets. This effect could be related to a more successful mucosal defence which in turn led to a lower level in systemic IgG production in piglets after weaning.

Bacillus cereus var. toyoi enhanced systemic immune response in piglets.

Probiotic bacteria have been suggested to stimulate the host immune system. In this study we evaluated the immunomodulatory effects of probiotic Bacillus cereus var. toyoi on the systemic immunity of piglets. A pool of 70 piglets was divided into a probiotic or control group. We determined the ratios of peripheral blood mononuclear cell (PBMC) subsets and measured proliferative responses and cytokine production of PBMCs and effects on vaccination responses. Blood samples of probiotic-treated piglets showed a significantly lower frequency of CD8(high)/CD3+ T cells and CD8(low)/CD3+ T cells and a significant higher CD4+/CD8+ ratio. IL-4 and IFN-gamma production of polyclonally stimulated PBMCs was on average higher in the probiotic group. Specific proliferative responses of PBMCs to Influenza vaccination antigens were significantly higher and antibody titers against H3N2 Influenza and Mycoplasma vaccination antigens were on average higher in the probiotic group. In conclusion, B. cereus var. toyoi therefore alters the immune status of piglets as indicated by changes in the ratios as well as functionalities of systemic immune cell populations.

Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic mice.

Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant.

Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections.

The emergence and increasing prevalence of multidrug-resistant bacterial pathogens emphasizes the need for new and innovative antimicrobial strategies. Lytic phages, which kill their host following amplification and release of progeny phage into the environment, may offer an alternative strategy for combating bacterial infections. In this study, however, we describe the use of a nonlytic phage to specifically target and deliver DNA encoding bactericidal proteins to bacteria. To test the concept of using phage as a lethal-agent delivery vehicle, we used the M13 phagemid system and the addiction toxins Gef and ChpBK. Phage delivery of lethal-agent phagemids reduced target bacterial numbers by several orders of magnitude in vitro and in a bacteremic mouse model of infection. Given the powerful genetic engineering tools available and the present knowledge in phage biology, this technology may have potential use in antimicrobial therapies and DNA vaccine development.

Validation of myocardial acceleration during isovolumic contraction as a novel noninvasive index of right ventricular contractility: comparison with ventricular pressure-volume relations in an animal model.

BACKGROUND: We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of left ventricular contractile function. In this study, we assessed the utility of IVA to measure right ventricular (RV) contractile function. METHODS AND RESULTS: We examined 8 pigs by using tissue Doppler imaging of the RV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (e(max)), preload recruitable stroke work, and dP/dt(max) by conductance catheterization. Animals were paced in the right atrium at a rate of 130 beats per minute (bpm). IVA was compared with elastance during contractility modulation by esmolol and dobutamine and during preload reduction and afterload increase by transient balloon occlusion of the inferior vena cava and pulmonary artery, respectively. Data were also obtained during incremental atrial pacing from 110 to 210 bpm. Esmolol led to a decrease in IVA and dP/dt(max). During dobutamine infusion, IVA, dP/dt(max), preload recruitable stroke work, and e(max) all increased significantly. During preload reduction and afterload increase, IVA remained constant up to a reduction of RV volume by 54% and an RV systolic pressure increase of 58%. Pacing up to a rate of 190 bpm led to a stepwise increase in IVA and dP/dt(max), with a subsequent fall at a pacing rate of 210 bpm. CONCLUSIONS: IVA is a measurement of RV contractile function that is unaffected by preload and afterload changes in a physiological range and is able to measure the force-frequency relation. This novel index may be ideally suited to the assessment of acute changes of RV function in clinical studies.