bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioid and Adjuvant Analgesics: Compared and Contrasted
Authors: Khan Mohammed Ilyas Ahmed , Walsh Declan , Brito-Dellan Norman
Published: May 2011

An adjuvant (or co-analgesic) is a drug that in its pharmacological characteristic is not necessarily primarily identified as an analgesic in nature but that has been found in clinical practice to have either an independent analgesic effect or additive analgesic properties when used with opioids. The therapeutic role of adjuvant analgesics (AAs) is to increase the therapeutic index of opioids by a dose-sparing effect, add a unique analgesic action in opioid-resistant pain, or reduce opioid side effects. A notable difference between opioids and AAs is that unlike opioids some AAs are associated with permanent organ toxicity, for example, nonsteroidal anti-inflammatory drugs (NSAIDs) and renal failure. It is impossible to predict in advance in a given individual what opioid dose they may require to control cancer pain. Most AAs have a ceiling effect for their analgesic actions, but often with continued dose-related toxicities and side effects (with the exception of glucocorticoids). The blood levels of opioids (and their metabolites) can be measured with great precision and accuracy. There is sometimes a role for drug blood levels of certain AAs, like tricyclic antidepressants or anticonvulsants when used for neuropathic pain. Age affects metabolism of most opioids. The therapeutic window of opioids is wide, with no ceiling effect. Most AAs (except corticosteroids) have a narrow therapeutic window. Naloxone is a pure opioid antagonist that competes and displaces opioids from their receptor sites. All clinically useful opioids are mu opioid receptor agonists. Not all routes of administration are available to all opioids. Adjuvant analgesics lack the versatility in routes of administration that opioids possess. Dosing flexibility is a major advantage when treating cancer-related pain with opioids. Dose flexibility is much less with AAs than opioids. Unlike opioids, the analgesic response is usually observed within hours to days of attaining an adequate dose with most AAs (1-2 days). Rotation among opioids is a useful therapeutic strategy to improve analgesic response or minimize toxicity. Most AAs are unsuitable for rescue dosing because of their pharmacological characteristics. The mu agonist side effect profile is similar among the different opioid agents, regardless of the route of administration. The appropriate use of AAs will reduce opioid-related side effects. No apparent tolerance to analgesia develops with AAs. Abrupt discontinuation of an opioid after chronic repeated use for more than a few days will cause a withdrawal syndrome of variable severity. Adjuvant analgesics are an essential tool in cancer pain.
Assessing the Five Factors of Personality in Adolescents
Authors: Ortet Generós , Ibáñez Manuel I. , Moya Jorge , Villa Helena , Viruela Ana , Mezquita Laura
Published: May 2011

This article presents the development of a junior version of the Spanish (Castilian) NEO Personality Inventory–Revised (JS NEO) suitable for adolescents aged 12 to 18 years. The psychometric properties of the new JS NEO were investigated using two samples of 2,733 and 983 adolescents in Spain. The results showed that the adult NEO-PI-R factor structure was replicated with the junior version of the inventory and that the reliabilities of the scales were adequate. The cross-form correlations between the junior and the adult versions of the questionnaires indicated good equivalence indices. Furthermore, a joint factor analysis of the JS NEO and the Big Five Questionnaire–Children (BFQ-C) provided additional evidence for the construct validity of the JS NEO.
Psychosocial Processes and Sexual Initiation Among Ghanaian Youth
Authors: McQuestion Michael , Ahiadeke Clement , Posner Jessica , Williams Timothy
Published: May 2011

This study models primary abstinence and age at first sex in a cross-sectional sample of Ghanaian youth aged 17 to 22 years. The aim is to examine how reproductive knowledge and social cognitive factors jointly affect the choice to initiate sex. Among males, the authors find that reproductive knowledge is negatively associated with abstinence. Its negative association, however, is moderated by the extent of adult support a respondent receives. Among females, reproductive knowledge is positively associated with abstinence. Its positive association is moderated by the extent of household sex communication. Correspondingly, when age at first sex is modeled, knowledge is a negative predictor among females. Its effects are mediated by household sex communication. A third social cognitive variable, perceived permissive peer attitudes about sex, is not associated with knowledge but is a protective factor for sexual initiation for both sexes. Though causal direction cannot be established, the results suggest that cognition affects sexual initiation both directly and through complex social mechanisms. The evidence provides theoretical support for comprehensive adolescent sexual and reproductive health interventions that promote abstinence and other safe sex behaviors through social as well as individual pathways.
Community walking can be assessed using a 10-metre timed walk test
Authors: Kempen JCE , de Groot V , Knol DL , Polman CH , Lankhorst GJ , Beckerman H
Published: May 2011

Background: A decline in mobility is a common feature of multiple sclerosis (MS). Community walking scales are used to categorize patients in their ability to move independently. The first purpose of this study was to determine which specific gait speed corresponded with the categories of the Modified Functional Walking Categories (MFWC). The second purpose was to determine the Minimally Important Change (MIC) in absolute gait speed using the MFWC and Expanded Disability Status Scale (EDSS) as external criteria.

Method: MS patients were measured six times in 6 years. Gait velocity was measured with the 10-metre timed walk test (10-m TWT), the severity of MS was determined with the EDSS, and community walking was assessed with the MFWC. For each category of the MFWC, Receiver Operating Characteristic (ROC) curves were used to find the best possible cut-off point on the 10-m TWT. The MIC in absolute gait speed was determined using a change of one category on the MFWC or one point on the EDSS.

Results: A strong relationship was found between gait speed and the MFWC; all areas under the ROC curves (AUCs) were between 0.74 and 0.86. The MIC in absolute gait speed could not be determined, because the AUCs were below the threshold of 0.70 and changes in gait speed were small.

Conclusions: Gait speed is related to community walking, but an MIC in absolute gait speed could not be determined using a minimally important change on the MFWC or the EDSS as external criteria.
Impact of rituximab on relapse rate and disability in neuromyelitis optica
Authors: Bedi Gurdesh S , Brown Andrew D , Delgado Sylvia R , Usmani Nida , Lam Byron L , Sheremata William A
Published: May 2011

Background: Neuromyelitis optica (NMO) is a severe demyelinating disease often leading to serious disability. Accumulating evidence now implicates humoral mechanisms in its pathogenesis. In the absence of an approved therapy, anti-inflammatory/immunosuppressant drugs have been used empirically for more than three decades. Recent evidence for a role of antibody to aquaporin-4 in the pathogenesis of NMO has led to the use of rituximab, a monoclonal antibody targeting the CD20 epitope on the entire B cell lineage.

Objectives: To evaluate the impact of rituximab on the relapse rate and disability in NMO.

Methods: This is an IRB approved retrospective longitudinal study of NMO patients treated with rituximab.

Results: We identified 53 patients with NMO, 23 of whom had been treated with rituximab. These patients (2 males, 21 females) had a mean age of 37.1 ± 14.6 years at the time of diagnosis. Eight of the 23 treated with rituximab were treatment naïve. All 23 were scheduled to receive infusions every six or 12 months after treatment initiation with a minimum follow-up of six months (median 32.5 months, range 7–63 months). Median relapse rate declined significantly from 1.87 relapses/patient per year to 0.0 relapses/patient per year. Kurtzke Expanded Disability Status Scale (EDSS) scores stabilized or improved in all patients. Use of rituximab is associated with a significant reduction in relapses and disability in patents with NMO.
Gender Differences in Competitive Orientations: Empirical Evidence from Ultramarathon Running
Authors: Frick Bernd
Published: May 2011

A large body of literature documents the existence of a considerable and persistent gender gap in competitiveness. Using longitudinal data from ultramarathon running covering the period 2005-2009, I first confirm the findings of most previous studies by demonstrating that on average the women’s races are indeed less competitive than the men’s contests. Closer inspection of the data, however, reveals that the gender gap has considerably narrowed over the years. Moreover, for men as well as for women, an increase in the number of contestants is not only associated with a better average performance but also with a lower performance dispersion. These findings are not compatible with the hypothesis that gender differences in competitiveness reflect evolved biological differences and/or psychological predispositions. It is, however, compatible with two other (complementary rather than substitute) hypotheses: Due to changing sociocultural conditions boys and girls are today socialized similarly in many parts of the world and due to the increasing returns to success (i.e., identical prize money levels and distributions) women are nowadays motivated to train as hard as comparably talented men.
Seminar Review: Sociocultural Practices and Epidemiology of Diabetic Foot Problem: Lessons From a Study in Chiang Mai University Hospital, Thailand
Authors: Rerkasem Kittipan
Published: May 2011

The data on sociocultural practices and epidemiology of diabetic foot problems are scarce in Thailand. This report used data found in a database with patients involved in multidisciplinary foot care. Of the 511 patients with diabetes, 475 (93.0%) patients had type 2 diabetes. The prevalence of foot ulcers in diabetic patients was 12.5% and the amputation rate was 1.4%. A total of 32.7% of patients suffered from neuropathic problems. Barefoot walking inside the house was found 55.4% of the time, and this seemed to link closely with Thai sociocultural practices. Improvement in foot care was a direct result of foot care education.
What Gender Is Science?
Authors: Charles Maria
Published: May 2011

Looking at science, technology, engineering, and mathematics (STEM) fields across countries challenges the assumption that women in more economically and culturally modern societies enjoy greater equality. Rather, freedom to choose a career may paradoxically cause women in affluent Western democracies to construct and replicate stereotypically gendered self-identities.
Sacco and Vanzetti and the Immigrant Threat
Authors: Alba Richard
Published: May 2011

The anti-immigrant sentiment in America in the 1920s, exemplified by the case against Sacco and Vanzetti, provides a pertinent reminder of the power of nativism as an establishment faces threatening social changes.
Embedded Sociologists
Authors: Nyseth Hollie , Shannon Sarah , Heise Kia , McElrath Suzy Maves
Published: May 2011

Armed with methodological skills and a healthy sociological imagination, a quarter of advanced-degree holding sociologists find work outside of the ivory tower. Sociology, as a whole, can benefit from increasing support and dialog across the academic/applied divide.
The Vanishing Catholic Priest
Authors: Conway Brian
Published: May 2011

Brian Conway examines the decline in vocations in Ireland and the U.S., and considers what it means for the future of international Catholicism.
Facebook’s Boundaries
Authors: Schoon Eric , Cain Cindy L.
Published: May 2011

Facebook was established to help students keep in touch after graduation, but now it’s being credited with major roles in everything from domestic elections to international uprisings. In its no-longer-insular world, Facebook transforms the private into the public.
The World Without Us?
Authors: Pike Diane
Published: May 2011

The future of higher education is up for grabs. Diane Pike finds, in two recent books, a call to action for social scientists and academics in the liberal arts.
Gender Norms in the Twilight Series
Authors: Hayes-Smith Rebecca
Published: May 2011

The hit series Twilight replicates gender stereotypes that sociologists have been debunking for decades. Rebecca Hayes-Smith highlights the gravity of making light of harmful gender messages.
The Poverty Fight
Authors: Soss Joe
Published: May 2011

It’s going to take more than smart ideas and good will to combat poverty; smarter policies and a political battle are necessary to disrupt politics as usual.
Stand Up Sociology
Authors: Smajda Jon , Brody Dylan
Published: May 2011

Humorist Dylan Brody weaves together personal, social, and political commentary in his writing and performances. Here he discusses television and political humor, the state of heroes today, and the transformative nature of storytelling.
Selling Feminism, Consuming Femininity
Authors: Gengler Amanda M.
Published: May 2011

For over half a century, magazines aimed at teens have been teaching girls how to inhabit stereotypical gender roles. Surprisingly, though the celebrities on the covers have changed, the messages have remained the same.
Regulation of TMPRSS6 by BMP6 and iron in human cells and mice
Authors: Meynard Delphine , Vaja Valentina , Sun Chia Chi , Corradini Elena , Chen Shanzhuo , López-Otín Carlos , Grgurevic Lovorka , Hong Charles C. , Stirnberg Marit , Gütschow Michael , Vukicevic Slobodan , Babitt Jodie L. , Lin Herbert Y.
Published: May 2011

Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA). Patients with IRIDA have inappropriately elevated levels of the iron regulatory hormone hepcidin, suggesting that TMPRSS6 is involved in negatively regulating hepcidin expression. Hepcidin is positively regulated by iron via the bone morphogenetic protein (BMP)-SMAD signaling pathway. In this study, we investigated whether BMP6 and iron also regulate TMPRSS6 expression. Here we demonstrate that, in vitro, treatment with BMP6 stimulates TMPRSS6 expression at the mRNA and protein levels and leads to an increase in matriptase-2 activity. Moreover, we identify that inhibitor of DNA binding 1 is the key element of the BMP-SMAD pathway to regulate TMPRSS6 expression in response to BMP6 treatment. Finally, we show that, in mice, Tmprss6 mRNA expression is stimulated by chronic iron treatment or BMP6 injection and is blocked by injection of neutralizing antibody against BMP6. Our results indicate that BMP6 and iron not only induce hepcidin expression but also induce TMPRSS6, a negative regulator of hepcidin expression. Modulation of TMPRSS6 expression could serve as a negative feedback inhibitor to avoid excessive hepcidin increases by iron to help maintain tight homeostatic balance of systemic iron levels.
Computed tomography measurements of parapneumonic effusion indicative of thoracentesis
Authors: Moffett B.K. , Panchabhai T.S. , Anaya E. , Nakamatsu R. , Arnold F.W. , Peyrani P. , Wiemken T. , Guardiola J. , Ramirez J.A.
Published: May 2011

Patients with parapneumonic effusions (PPE) measuring <1 cm by lateral decubitus radiograph (LDR) or <5 cm by lateral erect radiograph (LER) do not require thoracentesis. No such data exist for chest computed tomography (CCT). The objective of this study was to identify a PPE measurement by CCT that indicates the need for thoracentesis.

A secondary data analysis of two pneumonia databases was conducted to identify patients with PPE. Measurements of PPE using LDR, LER and CCT were correlated by linear regression analysis. The clinical outcome of community-acquired pneumonia patients managed with the newly defined CCT measurement was evaluated.

PPE was identified in 419 out of 1,460 patients with possible pneumonia. PPE measurements of 1 cm and 5 cm by LDR and LER, respectively, correlated with a measurement of 2.5 cm by CCT. Out of 95 patients with CCT measurements <2.5 cm, 31 poor clinical outcomes were reported: outcome was PPE related (n=1); outcome was PPE unrelated (n=26); and outcome was not evaluable (n=4). The single case of poor outcome also measured <1 cm by LDR.

This study indicates that patients with community-acquired pneumonia and a PPE measuring <2.5 cm by CCT can be managed without the need for thoracentesis.
Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years
Authors: Yao T-C. , Lee W-I. , Ou L-S. , Chen L-C. , Yeh K-W. , Huang J-L.
Published: May 2011

This study was undertaken to establish reference values of exhaled nitric oxide fraction (FeNO) and its determinants in healthy Asian children.

693 healthy Asian children aged 5–18 yrs were assessed using a single-breath onlineFeNOmeasurement (exhaled flow 50 mL·s−1), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E.

Geometric meanFeNOand the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation.FeNOwas positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. TheFeNOpredicted values were 1–2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9–10 ppb higher.

In conclusion, the upper limits of normalFeNOin Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.
Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study
Authors: Marshall N.S. , Delling L. , Grunstein R.R. , Peltonen M. , Sjöström C.D. , Karason K. , Carlsson L.M.S. , Hedner J. , Stenlöf K. , Sjöström L.
Published: May 2011

Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity.

The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgeryversusconventional treatment for the treatment of severe obesity and its complications (mean±sdbody mass index 41±5 kg·m−2). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs).

Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40–2.18)). In a range of multivariate models of mortality risk, controlling for ≤16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01–1.65)).

Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.
Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD
Authors: Pauwels N.S. , Bracke K.R. , Dupont L.L. , Van Pottelberge G.R. , Provoost S. , Vanden Berghe T. , Vandenabeele P. , Lambrecht B.N. , Joos G.F. , Brusselle G.G.
Published: May 2011

Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1β, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses.

We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1β antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionally, we measured the levels of IL-1α and IL-1β mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never-smokers, smokers without COPD and patients with COPD.

In CS-exposed mice, pulmonary inflammation was dependent on IL-1RI and could be significantly attenuated by neutralising IL-1α or IL-1β. Interestingly, CS-induced inflammation occurred independently of IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers.

These results suggest that not only IL-1β but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.
Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD
Authors: Buhl R. , Dunn L.J. , Disdier C. , Lassen C. , Amos C. , Henley M. , Kramer B.
Published: May 2011

Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the β2-agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability.

Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 μgq.d.(n=797) or tiotropium 18 μgq.d.(n=801) for 12 weeks.

After 12 weeks, the two treatments had similar overall effects on “trough” (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01versus1.43; p<0.001) and St George’s Respiratory Questionnaire (SGRQ) total score (least squares means 37.1versus39.2; p<0.001; raw mean change from baseline -5.1versus-3.0), and were significantly more likely to achieve clinically relevant improvements in these end-points (indacaterolversustiotropium odds ratios of 1.49 for TDI and 1.43 for SGRQ, both p<0.001). Adverse events were recorded for 39.7% and 37.2% of patients in the indacaterol and tiotropium treatment groups, respectively. The most frequent adverse events were COPD worsening, cough and nasopharyngitis.

Both bronchodilators demonstrated spirometric efficacy. The two treatments were well tolerated with similar adverse event profiles. Compared with tiotropium, indacaterol provided significantly greater improvements in clinical outcomes.
Obstructive sleep apnoea and metabolic impairment in severe obesity
Authors: Gasa M. , Salord N. , Fortuna A.M. , Mayos M. , Vilarrasa N. , Dorca J. , Montserrat J.M. , Bonsignore M.R. , Monasterio C.
Published: May 2011

Obstructive sleep apnoea (OSA) seems to worsen metabolism. This effect has not been evaluated in morbid obesity (MO). We hypothesised that the metabolic profile is more impaired in MO patients with OSA than in those without, and investigated whether any specific metabolic dysfunction is related to OSA in MO.

A prospective multicentre cross-sectional study was conducted in consecutive subjects before bariatric surgery. OSA was defined as apnoea/hypopnoea index (AHI) ≥15 by overnight polysomnography. Anthropometrical, blood pressure (BP) and fasting blood measurements were obtained the morning after. Metabolic syndrome (MetS) was defined according to National Cholesterol Education Program Adult Treatment Panel III modified criteria.

159 patients were studied: 72% were female and 72% had OSA. MetS prevalence was 70% in OSAversus36% in non-OSA (p<0.001). As AHI severity increased, metabolic parameters progressively worsened, even in those without type 2 diabetes (DM2). AHI was independently associated with systolic and diastolic BP, triglycerides and the percentage of glycosylated haemoglobin (HbA1c) in the total sample, and with systolic BP, high-density lipoprotein cholesterol and HbA1c in those samples without DM2. OSA increased the adjusted odds ratio of having MetS by 2.8 (95% CI 1.3–6.2; p=0.009).

In MO, OSA is associated with major metabolic impairment caused by higher BP and poorer lipid and glucose control, independent of central obesity or DM2.
Adhesive polypeptides of Staphylococcus aureus identified using a novel secretion library technique in Escherichia coli
Authors: Kylväjä Riikka , Kankainen Matti , Holm Liisa , Westerlund-Wikström Benita
Published: May 2011

Background

Bacterial adhesive proteins, called adhesins, are frequently the decisive factor in initiation of a bacterial infection. Characterization of such molecules is crucial for the understanding of bacterial pathogenesis, design of vaccines and development of antibacterial drugs. Because adhesins are frequently difficult to express, their characterization has often been hampered. Alternative expression methods developed for the analysis of adhesins, e.g. surface display techniques, suffer from various drawbacks and reports on high-level extracellular secretion of heterologous proteins in Gram-negative bacteria are scarce. These expression techniques are currently a field of active research. The purpose of the current study was to construct a convenient, new technique for identification of unknown bacterial adhesive polypeptides directly from the growth medium of theEscherichia colihost and to identify novel proteinaceous adhesins of the model organismStaphylococcus aureus.

Results

Randomly fragmented chromosomal DNA ofS. aureuswas cloned into a unique restriction site of our expression vector, which facilitates secretion of foreign FLAG-tagged polypeptides into the growth medium ofE. coliΔfliCΔfliD, to generate a library of 1663 clones expressing FLAG-tagged polypeptides. Sequence and bioinformatics analyses showed that in our example, the library covered approximately 32% of theS. aureusproteome. Polypeptides from the growth medium of the library clones were screened for binding to a selection ofS. aureustarget molecules and adhesive fragments of known staphylococcal adhesins (e.g coagulase and fibronectin-binding protein A) as well as polypeptides of novel function (e.g. a universal stress protein and phosphoribosylamino-imidazole carboxylase ATPase subunit) were detected. The results were further validated using purified His-tagged recombinant proteins of the corresponding fragments in enzyme-linked immunoassay and surface plasmon resonance analysis.

Conclusions

A new technique for identification of unknown bacterial adhesive polypeptides was constructed. Application of the method onS. aureusallowed us to identify three known adhesins and in addition, five new polypeptides binding to human plasma and extracellular matrix proteins. The method, here used onS. aureus, is convenient due to the use of soluble proteins from the growth medium and can in principle be applied to any bacterial species of interest.
Impact of a probiotic fermented milk in the gut ecosystem and in the systemic immunity using a non-severe protein-energy-malnutrition model in mice
Authors: Galdeano Carolina Maldonado , Núñez Ivanna Novotny , de Moreno de LeBlanc Alejandra , Carmuega Esteban , Weill Ricardo , Perdigón Gabriela
Published: May 2011

Background

Malnutrition affects the immune response, causing a decrease of defence mechanisms and making the host more susceptible to infections. Probiotics can reconstitute the intestinal mucosa and stimulate local and systemic immunity. The aim of this work was evaluate the effects of a probiotic fermented milk as a complement of a re-nutrition diet, on the recovery of the intestinal barrier, and mucosal and systemic immune functions in a murine model of non-severe protein-energy-malnutrition. Its potential protection against Salmonella enterica serovar Typhimurium (S. Typhimurium) infection was also analyzed.

Methods

Mice were undernourished and divided into 3 groups according to the dietary supplement received during re-nutrition (milk, probiotic fermented milk or its bacterial free supernatant) and compared to well-nourished and malnourished mice. They were sacrificed previous to the re-nutrition and 5 days post re-nutrition. The phagocytic activity of macrophages from spleen and peritoneum and the changes in the intestinal histology and microbiota were evaluated. Different immune cell populations and cytokine productions were analyzed in the small intestine tissues. The effect of the re-nutrition supplements on the systemic immunity using OVA antigen and against an infection with S. Typhimurium was also studied.

Results

Probiotic fermented milk was the most effective re-nutrition diet that improved the intestinal microbiota. Its administration also increased the number of IgA+ cells, macrophages and dendritic cells. The production of different cytokine (IFN-γ, TNF-α, IL-12) by these cells and the phagocytic activity in peritoneum and spleen was also increased. This re-nutrition diet also stimulated the systemic immune response against OVA antigen which was diminished after the malnutrition period and also improved the host response against S. Typhimurium, decreasing the spread of pathogenic bacteria to the liver and the spleen. The importance of the metabolites released during milk fermentation was also demonstrated through the analysis of the bacterial free supernatant obtained from the probiotic fermented milk, but the whole product showed the best effects in the parameters evaluated in this study.

Conclusions

The administration of probiotic fermented milk as a dietary supplement during the re-nutrition process in a murine immunodeficiency model by malnutrition could be a good adjuvant diet to improve the gut and systemic immune response for the protection against Salmonella infection.
Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression
Authors: Tieszen Chelsea R , Goyeneche Alicia A , Brandhagen BreeAnn N , Ortbahn Casey T , Telleria Carlos M
Published: May 2011

Background

Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR.

Methods

Dose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored in vitro by the capacity of Cdk2 to phosphorylate histone H1.

Results

MF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR.

Conclusions

Antiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR.
Advanced age, altered level of consciousness and a new diagnosis of diabetes are independently associated with hypernatreamia in hyperglycaemic crisis
Authors: Ekpebegh Chukwuma O , Longo-Mbenza Benjamin , Nge-Okwe Augustin , Ogbera Anthonia O , Tonjeni Nomawethu T
Published: May 2011

Background

There is limited literature on hypernatreamia in the setting of hyperglycaemic crisis. This is despite the fact that the presence of hypernatreamia may impact on the classification of hyperglycaemic crisis and its management particularly with regards to the nature of fluid therapy. We determined the prevalence of hypernatreamia and its associated factors at presentation for hyperglycaemic crisis.

Methods

This was a retrospective review of data for hyperglycaemic crisis admissions in Nelson Mandela Academic Hospital, Mthatha, South Africa. The prevalence of hypernatreamia (uncorrected Serum Sodium at presentation >145 mmol/L) was determined. Hyperosmolality was defined by calculated effective osmolality >320 mosmols/Kg. Multivariate logistic regression was undertaken using variables that were statistically significant in univariate analysis to ascertain those that were independently associated (Odds Ratio (OR) with 95% Confidence Interval (CI)) with hypernatreamia.

Results

The prevalence of hypernatreamia in our admissions for hyperglycaemic crisis was 11.7% (n = 32/273 including 171 females and 102 males). All admissions with hypernatreamia met the criteria for hyperosmolality. Age ≥ 60 years (OR = 3.9 95% CI 1.3-12.3; P = 0.018), Altered level of consciousness (OR = 8.8 95% CI 2.3-32.8; P < 0.001) and a new diagnosis of diabetes (OR = 3.7 95%CI 1.2-11.5; P = 0.025) were independently associated with hypernatreamia.

Conclusion

The prevalence rate of hypernatreamia in hyperglycaemic admissions was high with all hypernatreamic admissions meeting the criteria for hyperosmolality. Advanced age, altered conscious level and a new diagnosis of diabetes were independently associated with hypernatreamia.
Antibacterial and dermal toxicological profiles of ethyl acetate extract from Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae)
Authors: Mouokeu Raymond S , Ngono Rosalie AN , Lunga Paul K , Koanga Martin M , Tiabou Alambert T , Njateng Guy SS , Tamokou Jean DD , Kuiate Jules-Roger
Published: May 2011

Background

The emergence in recent years of numerous resistant strains of pathogenic bacteria to a range of formerly efficient antibiotics constitutes a serious threat to public health. Crassocephalum bauchiense, a medicinal herb found in the West Region of Cameroon is used to treat gastrointestinal infections as well as liver disorders. The ethyl acetate extract from the leaves of C. bauchiense was evaluated for its antibacterial activity as well as acute and sub-acute toxicities.

Methods

The plant extract was prepared by maceration in ethyl acetate. Its phytochemical screening was done by standard methods. The broth microdilution method was used to evaluate the in vitro antibacterial activity. The in vivo antibacterial activity of a gel formulation (0.05, 1 and 2% w/v) of this extract was evaluated using a Staphylococcus aureus-induced dermatitis in a murine model. Selected haematological and biochemical parameters were used to evaluate the dermal sub-acute toxicity of the extract in rats.

Results

Phytochemical screening of the C. bauchiense extract revealed the presence of alkaloids, phenols, tannins and sterols. In vitro antibacterial activities were observed against all the tested microorganisms (MIC = 0.04-6.25 mg/ml). Formulated extract-gel (2% w/v) and gentamycin (reference drug) eradicated the microbial infection after five days of treatment. A single dermal dose of this extract up to 32 g/kg body weight (bw) did not produce any visible sign of toxicity. Also, daily dermal application of the C. bauchiense extract gel formulation for 28 days did not show any negative effect, instead some biochemical parameters such as alanine aminotransferase (ALT and AST), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides were significantly (p < 0.05) affected positively.

Conclusion

These results indicate that the C. bauchiense ethyl acetate extract can be used safely for the treatment of some bacterial infections.
Integrating telecare for chronic disease management in the community: What needs to be done?
Authors: May Carl R , Finch Tracy L , Cornford James , Exley Catherine , Gately Claire , Kirk Sue , Jenkings K Neil , Osbourne Janice , Robinson A Louise , Rogers Anne , Wilson Robert , Mair Frances S
Published: May 2011

Background

Telecare could greatly facilitate chronic disease management in the community, but despite government promotion and positive demonstrations its implementation has been limited. This study aimed to identify factors inhibiting the implementation and integration of telecare systems for chronic disease management in the community.

Methods

Large scale comparative study employing qualitative data collection techniques: semi-structured interviews with key informants, task-groups, and workshops; framework analysis of qualitative data informed by Normalization Process Theory. Drawn from telecare services in community and domestic settings in England and Scotland, 221 participants were included, consisting of health professionals and managers; patients and carers; social care professionals and managers; and service suppliers and manufacturers.

Results

Key barriers to telecare integration were uncertainties about coherent and sustainable service and business models; lack of coordination across social and primary care boundaries, lack of financial or other incentives to include telecare within primary care services; a lack of a sense of continuity with previous service provision and self-care work undertaken by patients; and general uncertainty about the adequacy of telecare systems. These problems led to poor integration of policy and practice.

Conclusion

Telecare services may offer a cost effective and safe form of care for some people living with chronic illness. Slow and uneven implementation and integration do not stem from problems of adoption. They result from incomplete understanding of the role of telecare systems and subsequent adaption and embeddedness to context, and uncertainties about the best way to develop, coordinate, and sustain services that assist with chronic disease management. Interventions are therefore needed that (i) reduce uncertainty about the ownership of implementation processes and that lock together health and social care agencies; and (ii) ensure user centred rather than biomedical/service-centred models of care.
New Topoisomerase I mutations are associated with resistance to camptothecin
Authors: Gongora Céline , Vezzio-Vie Nadia , Tuduri Sandie , Denis Vincent , Causse Annick , Auzanneau Céline , Collod-Beroud Gwenaëlle , Coquelle Arnaud , Pasero Philippe , Pourquier Philippe , Martineau Pierre , Del Rio Maguy
Published: May 2011

Background

Topoisomerase I (TOP1) is a nuclear enzyme that catalyzes the relaxation of supercoiled DNA during DNA replication and transcription. TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecan's active metabolite). Irinotecan is widely used as an anti-cancer agent in the treatment of metastatic colon cancer. However, its efficacy is often limited by the development of resistance.

Methods

We previously established several SN38 resistant HCT116-derived clones to study the mechanisms underlying resistance to SN38. Here, we investigated whether resistance to SN38 in these cell lines could be linked to the presence of TOP1 mutations and changes in its expression and activity. Functional analyses were performed on these cell lines challenged with SN38 and we specifically monitored the double strands breaks with γH2AX staining and replication activity with molecular combing.

Results

In SN38 resistant HCT116 clones we identified three new TOP1 mutations, which are located in the core subdomain III (p.R621H and p.L617I) and in the linker domain (p.E710G) and are packed together at the interface between these two domains. The presence of these TOP1 mutations in SN38 resistant HCT116 cells did not modify TOP1 expression or intrinsic activity. Conversely, following challenge with SN38, we observed a decrease of TOP1-DNA cleavage complexes and a reduction in double-stranded break formation). In addition, we showed that SN38 resistant HCT116 cells present a strong decrease in the SN38-dependent asymmetry of replication forks that is characteristic of SN38 sensitive HCT116 cells.

Conclusions

These results indicate that the TOP1 mutations are involved in the development of SN38 resistance. We hypothesize that p.L617, p.R621 and p.E710 TOP1 residues are important for the functionality of the linker and that mutation of one of these residues is sufficient to alter or modulate its flexibility. Consequently, linker fluctuations could have an impact on SN38 binding by reducing the enzyme affinity for the drug.
Adipokine resistin predicts anti-inflammatory effect of glucocorticoids in asthma
Authors: Leivo-Korpela Sirpa , Lehtimäki Lauri , Vuolteenaho Katriina , Nieminen Riina , Kankaanranta Hannu , Saarelainen Seppo , Moilanen Eeva
Published: May 2011

Background

Adipokines are protein mediators secreted by adipose tissue. Recently, adipokines have also been involved in the regulation of inflammation and allergic responses, and suggested to affect the risk of asthma especially in obese female patients. We assessed if adipokines predict responsiveness to glucocorticoids and if plasma adipokine levels are associated with lung function or inflammatory activity also in non-obese (body mass index (BMI) ≤ 30 kg/m2) women with newly-diagnosed steroid-naïve asthma.

Methods

Lung function, exhaled NO, plasma levels of adipokines leptin, resistin, adiponectin and adipsin, and inflammatory markers were measured in 35 steroid-naïve female asthmatics and in healthy controls. The measurements were repeated in a subgroup of asthmatics after 8 weeks of treatment with inhaled fluticasone. Adipokine concentrations in plasma were adjusted for BMI.

Results

High baseline resistin concentrations were associated with a more pronounced decrease in serum levels of eosinophil cationic protein (ECP) (r = -0.745, p = 0.013), eosinophil protein X (EPX) (r = -0.733, p = 0.016) and myeloperoxidase (MPO) (r = -0.721, p = 0.019) during fluticasone treatment. In asthmatics, leptin correlated positively with asthma symptom score and negatively with lung function. However, no significant differences in plasma adipokine levels between non-obese asthmatics and healthy controls were found. The effects of resistin were also investigated in human macrophages in cell culture. Interestingly, resistin increased the production of proinflammatory factors IL-6 and TNF-α and that was inhibited by fluticasone.

Conclusions

High resistin levels predicted favourable anti-inflammatory effect of inhaled glucocorticoids suggesting that resistin may be a marker of steroid-sensitive phenotype in asthma. High leptin levels were associated with a more severe disease suggesting that the link between leptin and asthma is not restricted to obesity.
Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia
Authors: Hayashi Ken-Go , Ushizawa Koichi , Hosoe Misa , Takahashi Toru
Published: May 2011

Background

SERPINs (serine protease inhibitors) regulate proteases involving fibrinolysis, coagulation, inflammation, cell mobility, cellular differentiation and apoptosis. This study aimed to investigate differentially expressed genes of members of the SERPIN superfamily between healthy and atretic follicles using a combination of microarray and quantitative real-time PCR (QPCR) analysis. In addition, we further determined mRNA and protein localization of identified SERPINs in estradiol (E2)-active and E2-inactive follicles by in situ hybridization and immunohistochemistry.

Methods

We performed microarray analysis of healthy (10.7 +/- 0.7 mm) and atretic (7.8 +/- 0.2 mm) follicles using a custom-made bovine oligonucleotide microarray to screen differentially expressed genes encoding SERPIN superfamily members between groups. The expression profiles of six identified SERPIN genes were further confirmed by QPCR analysis. In addition, mRNA and protein localization of four SERPINs was investigated in E2-active and E2-inactive follicles using in situ hybridization and immunohistochemistry.

Results

We have identified 11 SERPIN genes expressed in healthy and atretic follicles by microarray analysis. QPCR analysis confirmed that mRNA expression of four SERPINs (SERPINA5, SERPINB6, SERPINE2 and SERPINF2) was greater in healthy than in atretic follicles, while two SERPINs (SERPINE1 and SERPING1) had greater expression in atretic than in healthy follicles. In situ hybridization showed that SERPINA5, SERPINB6 and SERPINF2 mRNA were localized in GCs of E2-active follicles and weakly expressed in GCs of E2-inactive follicles. SERPING1 mRNA was localized in both GCs and the theca layer (TL) of E2-inactive follicles and a weak hybridization signal was also detected in both GCs and TL of E2-active follicles. Immunohistochemistry showed that SERPINA5, SERPINB6 and SERPINF2 were detected in GCs of E2-active and E2-inactive follicles. SERPING1 protein was localized in both GCs and the TL of E2-active and E2-inactive follicles.

Conclusions

Our results demonstrate a characteristic expression of SERPIN superfamily member genes in bovine healthy and atretic follicles. The cell-type-and stage-specific expression of SERPINs may be associated with bovine follicular growth and atresia.