Folate Targeting Peptide Conjugates for Inflammatory Response Suppression.

BACKGROUND AND OBJECTIVE: Protein kinases known as mitogen-activated protein kinases (MAPKs) are responsible for regulating a wide variety of physiological cell responses by generating and release of inflammatory mediators. Suppressing these inflammatory mediators can be utilized to control the propagation of inflammation. During the course of this research, we created folate-targeted MK2 inhibitor conjugates and analyzed the antiinflammatory effects of these compounds. METHODS: Using RAW264.7 cells, which are generated from murine macrophages, as an in vitro model. We synthesize and evaluated a folate linked peptide MK2 inhibitor. The cytotoxicity was assessed using the ELISA kits, CCK- 8 test kit, NO concentration and inflammatory factors TNF-, IL-1, and IL-6. RESULTS: The cytotoxicity assay results suggested that the concentration for MK2 inhibitors less than 50.0 µM be non-toxic. The ELISA Kits also demonstrated that MK2 peptide inhibitor treatment significantly decreased the content of NO, TNF-, IL-1, and IL-6 in LPS-stimulated RAW264.7 cells. It was also demonstrated that a folate-targeted MK2 inhibitor was more effective than a non-targeted inhibitor. CONCLUSION: This experiment demonstrates that LPS-induced macrophages can produce oxidative stress and inflammatory mediators. According to our research, pro-inflammatory mediators can be reduced by targeting folate receptor- positive (FR+) macrophages with an FR-linked anti-inflammatory MK2 peptide inhibitor in vitro, and the uptake was FR-specific.

Microfiber Masses Recovered from Conventional Machine Washing of New or Aged Garments.

Synthetic textiles can shed numerous microfibers during conventional washing, but evaluating environmental consequences as well as source-control strategies requires understanding mass releases. Polyester apparel accounts for a large proportion of the polyester market, and synthetic jackets represent the broadest range in apparel construction, allowing for potential changes in manufacturing as a mitigation measure to reduce microfiber release during laundering. Here, detergent-free washing experiments were conducted and replicated in both front- and top-load conventional home machines for five new and mechanically aged jackets or sweaters: four from one name-brand clothing manufacturer (three majority polyester fleece, and one nylon shell with nonwoven polyester insulation) and one off-brand (100% polyester fleece). Wash water was filtered to recover two size fractions (>333 µm and between 20 and 333 µm); filters were then imaged, and microfiber masses were calculated. Across all treatments, the recovered microfiber mass per garment ranged from approximately 0 to 2 g, or exceeding 0.3% of the unwashed garment mass. Microfiber masses from top-load machines were approximately 7 times those from front-load machines; garments mechanically aged via a 24 h continuous wash had increased mass release under the same wash protocol as new garments. When published wastewater treatment plant influent characterization and microfiber removal studies are considered, washing synthetic jackets or sweaters as per this study would account for most microfibers entering the environment.

Successful use of volunteers to conduct school-located mass influenza vaccination clinics.

OBJECTIVE: To determine the feasibility of using volunteers to assist in school-located mass vaccination clinics for influenza. METHODS: A set of elementary school-based mass vaccination clinics was implemented in Carroll County, Maryland by the local health department in the 2005-2006 school year. In addition to using health department personnel, fiscal restraints necessitated using medical volunteers and lay volunteers to assist health professionals. The medical volunteers included physicians, nurses, and pharmacists, and were responsible for administering intranasal vaccine (live, attenuated influenza vaccine [LAIV]). We assessed the performance, as measured by the number of vaccinations administered, and effort expended by these volunteers. RESULTS: A total of 5319 (44%) of the 12,090 elementary school children in the county received LAIV. Of the estimated 3547 (66%) children eligible and consenting to receive a second dose, 3124 (88%) received it. In total, 8806 doses of LAIV were administered. Health department nurses worked 42 person-days and were assisted by medical and allied health professionals volunteering 87 person-days without compensation, totaling 581 person-hours spent in this effort. CONCLUSIONS: A mass school-located influenza vaccination program using medical and lay volunteers guided by health department nurses is feasible. Several issues were identified to improve future clinics and help make the program sustainable.

A pilot study of the effectiveness of a school-based influenza vaccination program.

OBJECTIVE: The objective of this study was to evaluate the feasibility of a school-based influenza immunization program. METHODS: Pupils and their families from 3 demographically similar elementary schools participated in this pilot, unblinded, controlled intervention study. Live attenuated influenza vaccine (FluMist) was made available to all eligible pupils in 1 target school during regular school hours. Two schools where vaccine was not offered served as control schools. All families from the 3 study schools were sent an anonymous questionnaire requesting 7-day recall data on fever or respiratory illness (FRI)-related medical visits, medications purchased, and days of school or paid work lost during the peak influenza week. Changes in weekly pupil absenteeism were also examined. RESULTS: One hundred eighty-five (40%) of the target school pupils received vaccine, of whom >50% were vaccinated < or =3 weeks before the influenza outbreak period. Questionnaires were returned by 43% to 51% of households. Significant (45-70%) relative reductions in FRI-related outcomes, including doctor visits by adults or children, prescription or other medicines purchased, and family schooldays or workdays missed, were observed for target school households, compared with control school households. The increases in absenteeism rates during the influenza outbreak period, compared with baseline rates earlier in the fall, were not significantly different between target and control schools. Within the target school, however, the increase in absenteeism rates was significantly smaller for the FluMist-vaccinated pupils, compared with the non-FluMist-vaccinated pupils. CONCLUSIONS: This school-based influenza immunization program was associated with significant reductions in FRI-related outcomes in households of pupils attending an intervention school. These results might have underestimated the potential impact of FluMist, because the majority of children received intraepidemic vaccination.

Cortical gamma-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking.

CONTEXT: Adaptations in gamma-aminobutyric acid type A (GABA(A))-benzodiazepine receptors contribute to the neurobiology of human alcohol dependence and withdrawal. OBJECTIVE: To study GABA(A)-benzodiazepine receptor adaptations in subjects with alcohol dependence over the first month of sobriety. DESIGN: Inpatients who were not receiving medication, were either smokers or nonsmokers, and had alcohol dependence completed 2 iodine I 123-labeled iomazenil single-photon emission computed tomographic scans: 1 scan at a mean +/- SD of 4.9 +/- 2.5 days of sobriety (n = 23) and 1 scan at a mean +/- SD of 29.8 +/- 7.6 days of sobriety (n = 20). Participants in a matched group of healthy subjects (n = 15) completed 1 single-photon emission computed tomographic scan. PARTICIPANTS: Men with alcohol dependence (n = 27) and a matched healthy comparison group (n = 15). MAIN OUTCOME MEASURES: (123)I-iomazenil single-photon emission computed tomographic images were converted to units of distribution volume (regional activity/free (123)I-iomazenil) and were analyzed using voxel-based statistical parametric mapping and regions of interest analyses. The relationships between (123)I-iomazenil distribution volume, clinical features of alcohol dependence, and smoking status were evaluated. RESULTS: (123)I-iomazenil uptake was elevated in several cortical regions, with a more prominent increase in nonsmokers with alcohol dependence as compared with smokers with alcohol dependence at 1 week of abstinence from alcohol. No significant differences were observed at 4 weeks of abstinence. At 1 week of abstinence, frontal (123)I-iomazenil uptake correlated with the severity of alcohol withdrawal and the number of days since the last alcoholic drink was consumed. No significant associations were observed for smokers with alcohol dependence. CONCLUSIONS: These data demonstrate time-dependent regulation of cortical GABA(A)-benzodiazepine receptors associated with the recovery from alcohol dependence. Higher GABA(A)-benzodiazepine receptor levels during acute withdrawal may reflect a compensation for reduced receptor function, which is thought to contribute to alcohol tolerance and withdrawal. The subsequent decline may reflect "normalization" of GABA(A) receptor function with sobriety. Smoking may attenuate GABA(A) receptor adaptations associated with alcohol dependence and may contribute to the comorbidity between alcoholism and smoking.