Practical Stability of Au25(SR)18-1/0/+1.

Superatom electron shell and/or geometric shell filling underlies the thermodynamic stability of coinage and alkali metal clusters in both theoretical and experimental results. Factors beyond simple shell filling contribute substantially to the lifetime of ligated clusters in solution. Such factors include the nature of the solvent, the atmosphere and the steric size of the ligand shell. Here we systematically lay out a 'practical' stability model for ligated metal clusters, which includes both shell-closing aspects and colloidal stability aspects. Cluster decomposition may follow either fusion or fission pathways. Solvent polarity can be determinative of the decomposition pathway.

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis.

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-) mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+)) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.

Radiofrequency heating pathways for gold nanoparticles.

This feature article reviews the thermal dissipation of nanoscopic gold under radiofrequency (RF) irradiation. It also presents previously unpublished data addressing obscure aspects of this phenomenon. While applications in biology motivated initial investigation of RF heating of gold nanoparticles, recent controversy concerning whether thermal effects can be attributed to nanoscopic gold highlight the need to understand the involved mechanism or mechanisms of heating. Both the nature of the particle and the nature of the RF field influence heating. Aspects of nanoparticle chemistry which may affect thermal dissipation include the hydrodynamic diameter of the particle, the oxidation state and related magnetism of the core, and the chemical nature of the ligand shell. Aspects of RF which may affect thermal dissipation include power, frequency and antenna designs that emphasize relative strength of magnetic or electric fields. These nanoparticle and RF properties are analysed in the context of three heating mechanisms proposed to explain gold nanoparticle heating in an RF field. This article also makes a critical analysis of the existing literature in the context of the nanoparticle preparations, RF structure, and suggested mechanisms in previously reported experiments.

Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition thought to reflect a failure of the enteral immune system to adequately regulate itself. Inflammatory stress drives upregulation of heat-shock proteins (HSPs), including the pro-inflammatory chaperone, HSP90. This protein sequesters the transcription factor, heat-shock factor 1 (HSF1) in the cytoplasm preventing transcription of a number of anti-inflammatory proteins. We hypothesized that inhibition of HSP90 would exert an anti-inflammatory effect and thereby attenuate intestinal inflammation in murine models of IBD. Inhibition of HSP90 with 17-allylaminogeldanamycin (17-AAG) reduced inflammation in acute dextran sodium sulfate and chronic CD45RB(High) colitis models coinciding with increased interleukin (IL)-10 production in the colon. Regulatory T cells (Tregs) from mice treated with 17-AAG demonstrated significantly greater suppressive capacity in vitro abolished in HSF1-/- or IL-10-/- cells. Finally, Tregs treated with 17-AAG exhibited increased nuclear localization of HSF1 with resultant upregulation of HSF1 response genes, including HSP70, HSP90 and IL-10.

Effect of purified ß-glucans derived from Laminaria digitata, Laminaria hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations, volatile fatty acids and pro-inflammatory cytokines in the gastrointestinal tract of pigs.

ß-Glucans have been identified as natural biomolecules with immunomodulatory activity. The first objective of the present study was to compare the effects of purified ß-glucans derived from Laminaria digitata, L. hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations and intestinal volatile fatty acid (VFA) production. The second aim was to compare the gene expression profiles of the markers of pro- and anti-inflammation in both unchallenged and lipopolysaccharide (LPS)-challenged ileal and colonic tissues. ß-Glucans were included at 250 mg/kg in the diets. The ß-glucans derived from L. hyperborea, L. digitata and S. cerevisiae all reduced the Enterobacteriaceae population (P<0·05) without influencing the lactobacilli and bifidobacteria populations (P>0·05) in the ileum and colon. There was a significant interaction between gastrointestinal region and ß-glucan source in the expression of cytokine markers, IL-1α (<0·001), IL-10 (P<0·05), TNF-α (P<0·05) and IL-17A (P<0·001). ß-Glucans did not stimulate any pro- or anti-inflammatory cytokine markers in the ileal epithelial cells. In contrast, the expression of a panel of pro- and anti-inflammatory cytokines (IL-1α, IL-10, TNF-α and IL-17A) was down-regulated in the colon following exposure to ß-glucans from all the three sources. However, the data suggest that the soluble ß-glucans derived from L. digitata may be acting via a different mechanism from the insoluble ß-glucans derived from L. hyperborea and S. cerevisiae, as the VFA profile was different in the L. digitata-treated animals. There was an increase in IL-8 gene expression (P<0·05) in the gastrointestinal tract from the animals exposed to L. digitata following an LPS ex vivo challenge that was not evident in the other two treatment groups. In conclusion, ß-glucans from both seaweed and yeast sources reduce Enterobacteriaceae counts and pro-inflammatory markers in the colon, though the mechanisms of action may be different between the soluble and insoluble fibre sources.

Effects of dietary ß-glucans supplementation on cytokine expression in porcine liver.

As dietary supplementation with ß-glucans can stimulate the innate immune response in the porcine gastrointestinal system (GIT), the aim of this study was to determine if the effects of ß-glucan supplementation extend beyond the GIT to systemic levels. Hence, the effects of dietary supplementation of ß-glucans derived from Laminara digitata, Laminara hyperborea, and Sacharomyces cerevisiae on cytokine expression in the porcine liver with or without ex vivo lipopolysaccharide (LPS) challenge were examined. No significant differences in gene expression were observed in the unchallenged liver tissue, but differences were observed in all supplementation groups in the LPS challenged tissue. Relative to the basal diet, IL-6 (P < 0.05) was less expressed in the S. cerevisiae supplementation group, IL-6 (P < 0.05) and TLR-4 (P < 0.05) were less expressed in the L. digitata supplementation group, and IL-10 (P = 0.06) and IL-1α (P = 0.02) were more expressed in the L. hyperborea supplementation group. There was a ≈ 3-fold increase in both IL-10 and IL-1α in the liver samples of L. hyperborea relative to the L. digitata supplementation groups (P < 0.01). The results indicate that supplementation with ß-glucans from both yeast and seaweed sources have systemic effects evidenced by changes in cytokine expression in the liver in response to LPS challenge; however, the cytokines affected varied according to the source of the ß-glucan.

Effects of dietary supplementation with Laminaria hyperborea, Laminaria digitata, and Saccharomyces cerevisiae on the IL-17 pathway in the porcine colon.

An unregulated T(h)17 inflammatory response has been highlighted as a major contributor to the underlying pathology of inflammatory bowel diseases (IBD) whereas regulatory T (T(REG)) cells) have been highlighted as pivotal in suppressing autoimmune and inflammatory responses in the gut. Following dietary supplementation, ß-glucans have been shown to reduce the T(h)17 signature molecule IL-17a in the porcine colon. To expand this observation we examined the effects of supplementing feeds with ß-glucans derived from seaweeds Laminaria hyperborea and Laminaria digitata and the yeast Saccharomyces cerevisiae on gene expression of a range of cytokines, receptors, and signal transducing molecules relevant to the T(h)17 and T(REG) pathways in the porcine colon. All sources of ß-glucans significantly decreased the expression of T(h)17-related cytokines (IL-17a, IL-17F, and IL-22), receptor IL23R, and IL-6. There was no alteration to the T(REG)-related target, Foxp3, or to TGF-ß, although a significant reduction in IL-10 was observed in the L. digitata supplementation group.

Effect of mast cell degranulation on chicken ileal ion transport in vitro.

Histamine is a primary mediator of the inflammatory response in mammals. Degranulation of intestinal mast cells results in the release of mast cell mediators such as histamine. Histamine stimulates epithelial ion transport in a range of mammalian tissues via specific histamine receptors. The aim of this study was to assess a potential role of tissue mast cells and of exogenous histamine in the regulation of ion transport in avian mucosa. Broiler chicken ileal histamine release and secretory responses to mast cell degranulation were determined in vitro with the use of ELISA and Ussing chamber techniques. Pharmacological degranulation of mucosal mast cells using compound 48/80 (15 microg/mL) resulted in histamine release and an immediate-onset transient increase in transmural short-circuit current. The response to compound 48/80 was subject to tachyphylaxis and was significantly reduced in the presence of the histamine H(1) antagonist mepyramine, but was unaffected by the cyclooxygenase inhibitor piroxicam. Prior incubation with the mast cell stabilizer ketotifen prevented compound 48/80-induced increase in transmural short-circuit current. In conclusion, degranulation of avian intestinal mast cells would appear to result in histamine release that stimulates epithelial ion transport via histamine H(1) receptor activation. Although prostaglandin E(2) is a potent secretagogue in the avian small intestine epithelium, prostanoid production appears to have little role to play in mast cell-mediated epithelial ion transport.

Comparison of plasma insulin levels after a mixed-meal challenge in children with and without intrauterine exposure to diabetes.

BACKGROUND: The diabetic intrauterine environment is a known risk factor for the development of diabetes in the offspring. OBJECTIVE: We compared anthropometric and metabolic characteristics of 41 nondiabetic children whose mothers developed diabetes either before (ODM, n = 19, 9.3 +/- 1.1 yr) or after (OPDM, n = 22, 9.5 +/- 1.3 yr) the pregnancy of interest. Maternal diabetes status was established from OGTT results before, during, and after the pregnancy of interest. DESIGN: After consuming a standardized diet for 2 d, a mixed-meal breakfast was given after an overnight fast. Fasting concentrations and responses of plasma glucose and insulin were evaluated using linear regression analyses to assess potential independent determinants of plasma insulin concentration at each time point. RESULTS: After adjustment for age and sex, there were no differences between ODM and OPDM children for maternal age at diagnosis, height, weight, body mass index, BMI z score, or percent body fat (dual energy x-ray absorptiometry). After adjusting for age, sex, percent body fat, and the corresponding glucose level at each time point, ODM had a lower plasma insulin level at the 15-min time point during the meal test than OPDM (P = 0.01). CONCLUSION: A lower initial insulin response to a standard mixed-meal challenge can be detected in nondiabetic ODM compared with OPDM children as early as 9 yr of age. This response may be another indicator for an attenuated early insulin response and explain the increased risk for diabetes in these children.

Drug use and HIV risk--related sex behaviors: a street outreach study of black adults.

BACKGROUND: Our street outreach project investigated the relationship between use of noninjecting drugs (alcohol, marijuana, cocaine) and human immunodeficiency virus (HIV) risk-related sex behaviors of black adults. The study focused on three HIV-related risks: multiple sex partners, unprotected sex, and drugs during sex. METHODS: Data for this study were collected in a street outreach community survey for a drug abuse and HIV intervention study in Birmingham, Ala. A total of 780 black men and women completed the survey. RESULTS: High-risk sex behaviors were far more prevalent among cocaine users than marijuana or alcohol users. A greater number of cocaine users reported having multiple sex partners, not using condoms, and using drugs during sex. Female cocaine users showed the same risk level for HIV infection as male cocaine users. CONCLUSIONS: Increased risk of HIV infection through sexual transmission is associated with use of noninjecting cocaine for both men and women. Condom use should be considered as a major component of HIV prevention programs.

AIDS knowledge among black drug users: an issue of reliability.

This study examined the reliability of an inventory measuring AIDS-related knowledge among 553 black drug users. Data were collected from a socially high-risk community in Birmingham, Alabama. The KR-20 reliability scores were computed from the inventory for each drug-use group. The KR-20 reliabilities ranged from .39 to .57. These findings may suggest that the inconsistent reports of the predictive power of AIDS knowledge among drug users reported in previous studies might be related to the low internal consistencies of the inventory.

Depressive symptoms as correlates of polydrug use for blacks in a high-risk community.

BACKGROUND: This study examined the relationship between depressive symptoms and polydrug use (alcohol, marijuana, and cocaine) among blacks in a high-risk community. METHODS: A street sample (N = 570) from four high-risk communities in Birmingham, Alabama, was collected through personal interviews. Interviewers asked respondents about their drug use behavior during the past 30 days, as well as about their depressive symptoms during the past week. RESULTS: Odds ratios and logistic regressions, adjusted for age and sex, were used to assess the relationship between depressive symptoms and drug and polydrug use (drug use involving cocaine). Results showed that depressive symptoms are significantly associated with polydrug use. However, depressive symptoms were not associated with alcohol use or with the combination of alcohol and marijuana use. CONCLUSIONS: Depressive symptoms are related to polydrug use involving cocaine, though the causal relationship is uncertain. Previous reports on depressive symptoms and alcohol or marijuana may be inconclusive.

Metoclopramide kinetics in patients with impaired renal function and clearance by hemodialysis.

Metoclopramide kinetics were examined in 24 adult patients with diminished renal function and in eight healthy subjects with normal renal function. Creatinine clearance correlated with metoclopramide plasma clearance, renal clearance, nonrenal clearance, and elimination t1/2. Regardless of renal function, renal clearance accounted for less than or equal to 21% of total plasma clearance. Nonrenal clearance was reduced in patients and accounted for most of the reduction in plasma clearance. The comparatively small plasma clearances in patients imply that maintenance doses should be reduced accordingly to avoid drug cumulation. Metoclopramide clearance by hemodialysis was also assessed in four patients. Metoclopramide losses from hemodialysis were relatively small compared to estimates of total body metoclopramide stores. Compensatory dosage increases are probably unnecessary for most patients. These data also suggest that hemodialysis is not likely to be effective in metoclopramide overdose.

Observation of coherent multiphoton processes in nuclear states.

We have used states of nuclear excitation to demonstrate coherent multiphoton processes that were the analogs of well-known effects occurring at optical frequencies. Success in exciting radio-frequency sidebands on hyperfine components of the 14.4-keV Mössbauer transition of (57)Fe is described. A distinctive feature of this experiment was that the absorbing foil was rigidly bound in a graphite sandwich intended to eliminate detrimental vibrations. A model is proposed that quantitatively explains these results in terms of coherently excited nuclear states and evidentially confirms the multiphoton nature of the sidebands observed in this experiment.

Cutaneous nonpulmonary Mycobacterium chelonei infection. Successful treatment with sulfonamides in an immunosuppressed patient.

A 52-year-old man, who had received immunosuppressive therapy for four years after renal transplantation, had a deep-set skin infection in his thigh caused by Mycobacterium chelonei. In vitro studies indicated that the organism was resistant to antimycobacterial agents but potentially sensitive to high-dose sulfonamide therapy. Repeated surgical excisions failed to eradicate the infection, as documented by histopathologic examination. The combination of a reduced dose of immunosuppressive medication and the administration of high-dose sulfonamide therapy resulted in clinical recovery.

Placenta previa and preeclampsia complicating the management of renal transplant patients.

Presented are three patients who have delivered full-term normal infants after renal transplants from living related donors. One patient had a placenta previa with excessive vaginal hemorrhage. Another patient manifested preeclampsia. Management of these and other complications should be aggressive and thorough with special precautions taken to preserve graft function. In our patients, pregnancy was not harmful to the renal transplant. No fetal complications from immunosuppressive drugs were noted and the patients' dosage requirements did not change. Counseling regarding family planning is essential in patients with renal transplant.