Chorioamnionitis induces enteric nervous system injury: effects of timing and inflammation in the ovine fetus.

BACKGROUND: Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model. METHODS: We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days. RESULTS: Four days of IA LPS exposure causes a decreased PGP9.5- and S100ß-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure. CONCLUSIONS: The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies.

In vitro exposure to Hymenoptera venom and constituents activates discrete ionotropic pathways in mast cells.

Calcium entry is central to the functional processes in mast cells and basophils that contribute to the induction and maintenance of inflammatory responses. Mast cells and basophils express an array of calcium channels, which mediate responses to diverse stimuli triggered by small bioactive molecules, physicochemical stimuli and immunological inputs including antigens and direct immune cell interactions. These cells are also highly responsive to certain venoms (such as Hymenoptera envenomations), which cause histamine secretion, cytokine release and an array of pro-inflammatory functional responses. There are gaps in our understanding of the coupling of venom exposure to specific signaling pathways such as activation of calcium channels. In the present study, we performed a current survey of a model mast cell line selected for its pleiotropic responsiveness to multiple pro-inflammatory inputs. As a heterogenous stimulus, Hymenoptera venom activates multiple classes of conductance at the population level but tend to lead to the measurement of only one type of conductance per cell, despite the cell co-expressing multiple channel types. The data show that ICRAC, IARC, and TRPV-like currents are present in the model mast cell populations and respond to venom exposure. We further assessed individual venom components, specifically secretagogues and arachidonic acid, and identified the conductances associated with these stimuli in mast cells. Single-cell calcium assays and immunofluorescence analysis show that there is heterogeneity of channel expression across the cell population, but this heterogeneity does not explain the apparent selectivity for specific channels in response to exposure to venom as a composite stimulus.

Gambian cultural beliefs, attitudes and discourse on reproductive health and mortality: Implications for data collection in surveys from the interviewer's perspective.

BACKGROUND: A community's cultural beliefs, attitudes and discourse can affect their responses in surveys. Knowledge of these cultural factors and how to comply with them or adjust for them during data collection can improve data quality. OBJECTIVE: This study describes implications of features of Gambian culture related to women's reproductive health, and mortality, when collecting data in surveys. METHODS: 13 in-depth interviews of female interviewers and a focus group discussion among male interviewers were conducted in two rural health and demographic surveillance systems as well as three key informant interviews in three regions in The Gambia. RESULTS: From the fieldworker's viewpoint, questions relating to reproduction were best asked by women as culturally pregnancies should be concealed, and menstruation is considered a sensitive topic. Gambians were reluctant to speak about decedents and the Fula did not like to be counted, potentially affecting estimation of mortality. Asking about siblings proved problematic among the Fula and Serahule communities. Proposals made to overcome these challenges were that culturally-appropriate metaphors and symbols should be used to discuss sensitive matters and to enumerating births/deaths singly instead of collecting summary totals, which had threatening connotations. This was as opposed to training interviewers to ask standardised and precise verbatim questions. CONTRIBUTION: This paper presents indigenous Gambian solutions by fieldworkers to culturally sensitive topics when collecting pregnancy outcomes and mortality data in demographic and health surveys. For researchers collecting maternal mortality data, it highlights the potential shortcomings of the sibling history methodology.

Male patients affected by mosaic PCDH19 mutations: five new cases.

Pathogenic variants in the PCDH19 gene are associated with epilepsy, intellectual disability (ID) and behavioural disturbances. Only heterozygous females and mosaic males are affected, likely due to a disease mechanism named cellular interference. Until now, only four affected mosaic male patients have been described in literature. Here, we report five additional male patients, of which four are older than the oldest patient reported so far. All reported patients were selected for genetic testing because of developmental delay and/or epilepsy. Custom-targeted next generation sequencing gene panels for epilepsy genes were used. Clinical data were collected from medical records. All patients were mosaic in blood for likely pathogenic variants in the PCDH19 gene. In most, clinical features were very similar to the female phenotype, with normal development before seizure onset, which occurred between 5 and 10 months of age, clustering of seizures and sensitivity to fever. Four out of five patients had mild to severe ID and behavioural problems. We reaffirm the similarity between male and female PCDH19-related phenotypes, now also in a later phase of the disorder (ages 10-14 years).

TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection.

Calcium signaling in phagocytes is essential for cellular activation, migration, and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2-/- mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with wild-type (WT) mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2-/- macrophages enhanced mitogen-activated protein kinase and NADPH-oxidase activities, compared with WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages and consequently decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa.

CO2 exposure as translational cross-species experimental model for panic.

The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral-emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.

Generation and Functional Evaluation of Designer Monoterpene Synthases.

Monoterpene synthases are highly versatile enzymes that catalyze the first committed step in the pathways toward terpenoids, the structurally most diverse class of plant natural products. Recent advancements in our understanding of the reaction mechanism have enabled engineering approaches to develop mutant monoterpene synthases that produce specific monoterpenes. In this chapter, we are describing protocols to introduce targeted mutations, express mutant enzyme catalysts in heterologous hosts, and assess their catalytic properties. Mutant monoterpene synthases have the potential to contribute significantly to synthetic biology efforts aimed at producing larger amounts of commercially attractive monoterpenes.

Cost and impact of policies to remove and reduce fees for obstetric care in Benin, Burkina Faso, Mali and Morocco.

BACKGROUND: Across the Africa region and beyond, the last decade has seen many countries introducing policies aimed at reducing financial barriers to obstetric care. This article provides evidence of the cost and effects of national policies focussed on improving financial access to caesarean and facility deliveries in Benin, Burkina Faso, Mali and Morocco. METHODS: The study uses a comparative case study design with mixed methods, including realist evaluation components. This article presents results across 14 different data collection tools, used in 4-6 research sites in each of the four study countries over 2011-13. The methods included: document review; interviews with key informants; analysis of secondary data; structured extraction from medical files; cross-sectional surveys of patients and staff; interviews with patients and observation of care processes. RESULTS: The article finds that the policies have contributed to continued increases in skilled birth attendance and caesarean sections and a narrowing of inequalities in all four countries, but these trends were already occurring so a shift cannot be attributed solely to the policies. It finds a significant reduction in financial burdens on households after the policy, suggesting that the financial protection objectives may have been met, at least in the short term, although none achieved total exemption of targeted costs. Policies are domestically financed and are potentially sustainable and efficient, and were relatively thoroughly implemented. Further, we find no evidence of negative effects on technical quality of care, or of unintended negative effects on untargeted services. CONCLUSIONS: We conclude that the policies were effective in meeting financial protection goals and probably health and equity goals, at sustainable cost, but that a range of measures could increase their effectiveness and equity. These include broadening the exempted package (especially for those countries which focused on caesarean sections alone), better calibrated payments, clearer information on policies, better stewardship of the local health system to deal with underlying systemic weaknesses, more robust implementation of exemptions for indigents, and paying more attention to quality of care, especially for newborns.

Differential regulation of calcium signalling pathways by components of Piper methysticum ('Awa).

Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and -insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava.

Strengths and weaknesses in the implementation of maternal and perinatal death reviews in Tanzania: perceptions, processes and practice.

OBJECTIVES: Tanzania institutionalised maternal and perinatal death reviews (MPDR) in 2006, yet there is scarce evidence on the extent and quality of implementation of the system. We reviewed the national policy documentation and explored stakeholders' involvement in, and perspectives of, the role and practices of MPDR in district and regional hospitals, and assessed current capacity for achieving MPDR. METHODS: We reviewed the national MPDR guidelines and conducted a qualitative study using semi-structured interviews. Thirty-two informants in Mara Region were interviewed within health administration and hospitals, and five informants were included at the central level. Interviews were analysed for comparison of statements across health system level, hospital, profession and MPDR experience. RESULTS: The current MPDR system does not function adequately to either perform good quality reviews or fulfil the aspiration to capture every facility-based maternal and perinatal death. Informants at all levels express differing understandings of the purpose of MPDR. Hospital reviews fail to identify appropriate challenges and solutions at the facility level. Staff are committed to the process of maternal death review, with routine documentation and reporting, yet action and response are insufficient. CONCLUSION: The confusion between MPDR and maternal death surveillance and response results in a system geared towards data collection and surveillance, failing to explore challenges and solutions from within the remit of the hospital team. This reduces the accountability of the health workers and undermines opportunities to improve quality of care. We recommend initiatives to strengthen the quality of facility-level reviews in order to establish a culture of continuous quality of care improvement and a mechanism of accountability within facilities. Effective facility reviews are an important peer-learning process that should remain central to quality of care improvement strategies.

Fatigue and heat sensitivity in patients with multiple sclerosis.

OBJECTIVES: Fatigue is one of the most common and troubling symptoms of multiple sclerosis (MS), and heat is often reported as a trigger. Although it is assumed that this heat sensitivity is specific for MS, the evidence for disease specificity is limited. We studied the relationship between fatigue, heat sensitivity, and environmental temperature, and its specificity for MS. MATERIALS AND METHODS: We compared 88 MS patients with 76 patients with ulcerative colitis (UC), another chronic auto-immune disease. As most important outcome measures, heat sensitivity, physical fatigue, mental fatigue, environmental temperature, and ambient UV-light levels were determined. RESULTS: More patients with MS reported heat sensitivity for fatigue, compared to patients with UC (53.4% vs 35.5%, respectively, P = 0.016). However, heat-sensitive patients were equally fatigued as heat-insensitive patients. Climatological data, including day temperature and amount of ambient UV light, were not related to fatigue in both heat-sensitive and heat-insensitive patients with MS. CONCLUSIONS: Our findings support the assumption that heat sensitivity regarding fatigue has an MS-specific component. Although patients with MS experience a relationship between environmental temperature and fatigue, objective assessment by climatological data could not confirm this.

Diagnostic accuracy of rapid phIGFBP-I assay for predicting preterm labor in symptomatic patients.

OBJECTIVE: To estimate sensitivity, specificity, positive and negative predictive values (PPV, NPV) of insulin-like growth factor binding protein-1 (phIGFBP-1) test in predicting preterm delivery in women with symptoms of preterm labor. Secondary objectives were to compare test characteristics of the phIGFBP-1 and fetal fibronectin (fFN) tests. STUDY DESIGN: Labor and delivery units in two Calgary hospitals. Subjects were 349 women with suspected labor between 24 and 35 weeks gestational age (GA). Women had cervical phIGFBP-1 test +/- and fFN testing. Sensitivity, specificity, PPV and NPV were estimated. Primary outcome was birth <37 weeks GA. RESULT: Sensitivity of phIGFBP-1 test for delivery <37 weeks was 0.39; specificity, 0.76; PPV, 0.24; NPV, 0.86. NPV of phIGFBP-1 did not differ greatly from that of fFN testing (0.88). CONCLUSION: NPV did not differ between phIGFBP-1 and fFN for delivery <37 weeks. Neither test improves on pretest probability of delivery <37 weeks, so clinicians must decide whether the use of either test is justified.

[An endodontic ultrasonic system for apical endodontic surgery]. / Ultrasone wortelpuntpreparatie bij een chirurgische apicale endodontische behandeling.

Apical endodontic surgery is applied frequently following a failed conventional endodontic treatment. The apical preparation can be carried out conventionally using a round bur or using an endodontic ultrasonic system. The purpose of this study was to compare the outcome of the 2 treatment options by a randomized prospective clinical study. Patients (n=399) were at random allocated to treatment using a conventional round bur or using an ultrasonic system (P-max Newtron) according to a for the rest similar treatment protocol. One year post treatment, the treatment outcomes were determined by 2 oral and maxillofacial surgeons, blinded for the treatment option. Adequate follow-up data were obtained from 290 patients. The overall success rate was 71% in the patients treated conventionally and 81% in the patients treated using the ultrasonic system. In molar teeth, the difference in success rate was statistically significant.

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions.

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.

The gastrointestinal tract as target of steroid hormone action: quantification of steroid receptor mRNA expression (AR, ERalpha, ERbeta and PR) in 10 bovine gastrointestinal tract compartments by kinetic RT-PCR.

We have examined the tissue-specific mRNA expression pattern of androgen receptor (AR), both estrogen receptor (ER) subtypes ERalpha and ERbeta and progestin receptor (PR) in 10 bovine gastrointestinal compartments. Goal of this study was to evaluate the deviating tissue sensitivities and the influence of the estrogenic active preparation Ralgro on the compartment-specific expression regulation. Ralgro contains Zeranol which shows strong estrogenic and anabolic effects. Eight heifers were treated for 8 weeks with Ralgro at different dosages (0, 1, 3, and 10 times). To quantify the very low abundant steroid receptor mRNA transcripts sensitive and reliable real-time (kinetic) reverse transcription (RT)-PCR quantification methods were validated on the LightCycler. Expression results indicate the existence of AR and both ER subtypes in all 10 gastrointestinal compartments. PR receptor was expressed at very low abundancy. Gastrointestinal tissues exhibit a specific ERalpha and ERbeta expression pattern with high expression levels for both subtypes in rectum, colon and ileum. With increasing Zeranol concentrations a significant down-regulation for ERalpha and ERbeta was observed in jejunum (P<0.001 and <0.05, respectively). Significant up-regulations under estrogen treatment could be shown in abomasum for ERalpha (P<0.05) and in rectum for ERbeta (P<0.001). The authors conclude, that especially estrogens and the expression of their corresponding receptor subtypes may play an important role in the modulation and regulation in gastric as well as gut functions, cell proliferation and possibly in the pathophysiology of cell cancer. The different expression patterns of ERalpha and ERbeta can be regarded as support of the hypothesis that the subtype proteins may have different biological functions in the gastrointestinal tract. AR and PR seem to be not estrogen dependent.

Quantitative assessment of foetal exposure to trenbolone acetate, zeranol and melengestrol acetate, following maternal dosing in rabbits.

1. Residues of commonly used growth-promoting agents found in animal meat can be hormonally active and they have been implicated as possible endocrine disruptors in man. Although these compounds could be potentially detrimental to the developing foetus, it is not clear whether and to what extent they pass through placental barrier. 2. This issue was addressed using the rabbit as an animal model. Pregnant rabbits were treated with trenbolone acetate, zeranol or melengestrol acetate beginning at gestation day 14. Levels of active substances in plasma were screened by means of specific ELISA systems. The residues of parent compounds and their metabolites were quantified in maternal and foetal tissues on gestation day 27 using validated, sensitive HPLC/ELISA methods. 3. All three compounds crossed the placental barrier and were detectable in foetal tissues. The extent of tissue concentration varied depending on the compound and tissue analysed. Gender differences were observed in some instances.

Estradiol-17beta is produced in bovine corpus luteum.

The aim of this study was to investigate the expression of cytochrome P450 aromatase (aromatase) mRNA, its activity, and estradiol-17beta (estradiol) secretion in bovine corpus luteum (CL) during the estrous cycle. Expression of aromatase mRNA was examined in CL at the early, mid, late, and regressed luteal stages by using a reverse transcription-polymerase chain reaction. Aromatase mRNA was detected in all luteal stages examined, although aromatase expression was significantly lower during the early and regressed luteal phases compared to the mid and late luteal phases. Moreover, cultured midluteal cells clearly converted exogenous [(3)H]androstenedione into estradiol, and an aromatase inhibitor significantly inhibited this conversion. To characterize the local release of estradiol within the CL during the estrous cycle, an in vitro microdialysis system (MDS) of CL was conducted. Estradiol in MDS perfusate was confirmed by a reverse-phase high-performance liquid chromatography in combination with enzyme immunoassays. Basal release of estradiol from microdialyzed CL did not change during the estrous cycle. Additionally, when freshly prepared midluteal cells were exposed to estradiol (10(-14) to 10(-9) M), estradiol stimulated prostaglandin (PG) F(2alpha) secretion (P < 0.05), although it did not affect progesterone and oxytocin secretion. The overall results indicate that estradiol is produced locally in bovine CL throughout the estrous cycle, and they suggest that estradiol plays a role in regulating PGF(2alpha) production in CL as an autocrine/paracrine factor.

Studies on the antibody response of Lama glama--evaluation of the binding capacity of different IgG subtypes in ELISAs for clenbuterol and BSA.

Camelidae are known to produce three subtypes of immunoglobulin G (IgG), two of which are devoid of light chains. Two llamas (Lama glama) were immunised against clenbuterol-bovine serum albumin (BSA). Enzyme-linked immunosorbent assays (ELISAs) for clenbuterol and BSA on the basis of protein A-coated microtitration plates were established to investigate the titre development. Three subclasses of IgG (IgG(1): 29+66KDD, IgG(2): 52KDD, IgG(3): 56KDD) depending on their different binding properties to protein A and protein G could be separated chromatographically. Only IgG(1), which consists of conventional four-chain antibodies, bound to clenbuterol, whereas all forms of heavy-chain antibodies merely bound BSA.

Tissue-specific expression pattern of estrogen receptors (ER): quantification of ER alpha and ER beta mRNA with real-time RT-PCR.

We have examined the tissue-specific mRNA expression of ER alpha and ER beta in various bovine tissues using real-time RT-PCR. The goal of this study was to evaluate the deviating tissue sensitivities and the influence of the estrogenic active preparation RALGRO on the tissue-specific expression and regulation of both ER subtypes. RALGRO contains Zeranol (alpha-Zearalanol), a derivative of the mycotoxin Zearalenon, shows strong estrogenic and anabolic effects, and exhibits all symptoms of hyperestrogenism, in particular reproductive and developmental disorders. Eight heifers were treated over 8 weeks with multiple-dose implantations (0x, 1x, 3x, 10x) of Zeranol. Plasma Zeranol concentration, measured by enzyme immunoassay, of multiple treated heifers was elevated. To quantify ER alpha and ER beta transcripts also in low-abundant tissues, sensitive and reliable real-time RT-PCR quantification methods were developed and validated on the LightCycler. Expression results indicate the existence of both ER subtypes in all 15 investigated tissues. All tissues exhibited a specific ER alpha and ER beta expression pattern and regulation. With increasing Zeranol concentrations, a significant downregulation of ER alpha mRNA expression could be observed in jejunum (p<0.001) and kidney medulla (p<0.05). These data support the hypothesis that ER beta may have different biological functions than ER alpha, especially in kidney and jejunum.

International nursing faculty exchange model: a Chile-USA case.

International faculty-exchange programmes can be cost-effective methods for faculty development and enhanced student learning. Despite the increasing interest in international nursing exchanges, the literature on faculty exchanges is limited. This article examines a case study of a successful international nursing faculty-exchange programme between a university in Chile and one in the United States of America (USA), based on a model for international faculty exchange. The model includes the components of pre-exchange planning, academic activities, socio-cultural events and evaluation of outcomes. Communication is at the centre of the model and ideally should be continuous, bilateral, flexible and technological. Examples from the case study illustrate teaching strategies and ongoing education of faculty. The article concludes with suggestions for successful international nursing faculty exchanges.