Effects of tetrodotoxin and ion replacements on the short-circuit current induced by Escherichiacoli heat stable enterotoxin across small intestine of the gerbil (Gerbillus cheesmani)

The effects of mucosally added Escherichia coli heat stable enterotoxin (STa 30 ng ml-1) on the basal short-circuit current (Isc in µA cm-2) across stripped and unstripped sheets of jejuna and ilea taken from fed, starved (4 days, water ad lib) and undernourished (50% control food intake for 21 days) gerbil (Gerbillus cheesmani) were investigated. The effect of neurotoxin tetrodotoxin (TTX 10 µM) and the effects of replacing chloride by gluconate or the effects of removing bicarbonate from bathing buffers on the maximum increase in Isc induced by STa were also investigated. The maximum increase in Isc which resulted from the addition of STa were significantly higher in jejuna and ilea taken from starved and undernourished gerbils when compared with the fed control both using stripped and unstripped sheets. In the two regions of the small intestine taken from fed and starved animals TTX reduced the maximum increase in Isc induced by STa across unstripped sheets only. Moreover in jejuna and ilea taken from undernourished gerbils TTX reduced significantly the maximum increase in Isc induced by STa across stripped and unstripped sheets. Replacing chloride by gluconate decreased the maximum increase in Isc induced by STa across jejuna and ilea taken from undernourished gerbils only. Removing bicarbonates from bathing buffer decreased the maximum increase in Isc across the jejuna and ilea taken from starved and undernourished gerbils.

Current genetic data do not improve the prediction of type 2 diabetes mellitus: the CoLaus study.

CONTEXT: Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE: The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN: This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS: The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE: Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS: Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS: In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.

Epidemiology of leishmaniasis in Ecuador: current status of knowledge - A review

Although leishmaniasis is regarded as a significant health problem in Ecuador by the Ministry of Health, and the incidence has increased over the last years, an official map on the geographic distribution of disease and sand fly vectors or a control strategy do not exist yet. This article reviews the current situation based on published information to improve our knowledge and understand the epidemiological situation of leishmaniasis in Ecuador in order to help future research and to develop a national control strategy. The disease is endemic in most provinces throughout Pacific coastal region, Amazonian lowlands, and some inter-Andean valleys with a total 21,805 cases reported during 1990-2003. Whereas cutaneous leishmaniasis (CL) is found throughout Ecuador, mucocutaneous leishmaniasis (MCL) appears to be restricted to the Amazon region; one, parasitologically unconfirmed case of visceral form was reported in 1949. Most human infections are caused by Leishmania (Viannia) spp., which is distributed in the subtropical and tropical lowlands; infections due to L. (Leishmania) spp. are found in the Andean highlands and in the Pacific lowlands as well. The proven vectors are Lutzomyia trapidoi and Lu. ayacuchensis. Canis familiaris, Sciurus vulgaris, Potos flavus, and Tamandua tetradactyla have been found infected with Leishmania spp. It is estimated that around 3000-4500 people may be infected every year, and that 3.1 to 4.5 millions people are estimated to be at risk of contracting leishmaniasis.

The Quorum-Sensing Molecules Farnesol/Homoserine Lactone and Dodecanol Operate via Distinct Modes of Action in Candida albicans.

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C(12)-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C(12)-homoserine lactone, may be used by other quorum-sensing molecules.

Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury.

The H(+)-gated acid-sensing ion channels (ASICs) are expressed in dorsal root ganglion (DRG) neurones. Studies with ASIC knockout mice indicated either a pro-nociceptive or a modulatory role of ASICs in pain sensation. We have investigated in freshly isolated rat DRG neurones whether neurones with different ASIC current properties exist, which may explain distinct cellular roles, and we have investigated ASIC regulation in an experimental model of neuropathic pain. Small-diameter DRG neurones expressed three different ASIC current types which were all preferentially expressed in putative nociceptors. Type 1 currents were mediated by ASIC1a homomultimers and characterized by steep pH dependence of current activation in the pH range 6.8-6.0. Type 3 currents were activated in a similar pH range as type 1, while type 2 currents were activated at pH < 6. When activated by acidification to pH 6.8 or 6.5, the probability of inducing action potentials correlated with the ASIC current density. Nerve injury induced differential regulation of ASIC subunit expression and selective changes in ASIC function in DRG neurones, suggesting a complex reorganization of ASICs during the development of neuropathic pain. In summary, we describe a basis for distinct cellular functions of different ASIC types in small-diameter DRG neurones.

Plasma membrane cyclic nucleotide gated calcium channels control land plant thermal sensing and acquired thermotolerance.

Typically at dawn on a hot summer day, land plants need precise molecular thermometers to sense harmless increments in the ambient temperature to induce a timely heat shock response (HSR) and accumulate protective heat shock proteins in anticipation of harmful temperatures at mid-day. Here, we found that the cyclic nucleotide gated calcium channel (CNGC) CNGCb gene from Physcomitrella patens and its Arabidopsis thaliana ortholog CNGC2, encode a component of cyclic nucleotide gated Ca(2+) channels that act as the primary thermosensors of land plant cells. Disruption of CNGCb or CNGC2 produced a hyper-thermosensitive phenotype, giving rise to an HSR and acquired thermotolerance at significantly milder heat-priming treatments than in wild-type plants. In an aequorin-expressing moss, CNGCb loss-of-function caused a hyper-thermoresponsive Ca(2+) influx and altered Ca(2+) signaling. Patch clamp recordings on moss protoplasts showed the presence of three distinct thermoresponsive Ca(2+) channels in wild-type cells. Deletion of CNGCb led to a total absence of one and increased the open probability of the remaining two thermoresponsive Ca(2+) channels. Thus, CNGC2 and CNGCb are expected to form heteromeric Ca(2+) channels with other related CNGCs. These channels in the plasma membrane respond to increments in the ambient temperature by triggering an optimal HSR, leading to the onset of plant acquired thermotolerance.

Pacemakers and magnetic resonance imaging: Current status and survey in Switzerland.

Electromagnetic fields arising from magnetic resonance imaging (MRI) can cause various clinically relevant functional disturbances in patients with cardiac pacemakers. Consequently, an implanted pacemaker is generally considered a contraindication for an MRI scan. With approximately 60 million MRI scans performed worldwide per year, MRI may be indicated for an estimated majority of pacemaker patients during the lifetime of their pacemakers. The availability of MR conditional pacemakers with CE labelling is of particular advantage since they allow the safe use of pacemakers in MRI. In this article the current state of knowledge on pacemakers and MR imaging is discussed. We present the results of a survey conducted among Swiss radiologists to assess current practice in patients with pacemakers.

Reliability of current estimates of schistosomiasis prevalence in the Rainforest Zone of the state of Pernambuco, Northeastern Brazil

The Program for Schistosomiasis Control within the Unified Health System (PCE-SUS) was implemented by 1999 in the Rainforest Zone or "Zona da Mata" of Pernambuco (ZMP) aiming to carry out biennial stool surveys of whole populations through municipal health organs followed by treatment of the positives through the local units of the Family Health Program (PSF). Yearly reports from the Health Department of Pernambuco State (SES/PE) from 2002 to 2004 on the PCE-SUS surveys were assessed to evaluate whether the current estimates of prevalence in the municipalities of the ZMP are based on reliable samples so as to allow considerations on the real situation of schistosomiasis in that area. The surveys carried out in that period did not follow the major principles underlying sampling design, thus posing problems in both precision and validity of the estimates. Only 12 out of 43 municipalities had minimally reliable estimates: five with moderate prevalence (10-50%) and seven with low prevalence (< 10%). Surveys with appropriate sampling procedures aimed either at representative target groups (school-aged children) or communities are recommended for the ZMP and other endemic areas not only to provide reliable information on the current situation of schistosomiasis but also to plan adequate control strategies.

Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts.

Prostacyclin and its mimetics are used therapeutically for the treatment of pulmonary hypertension. These drugs act via cell surface prostacyclin receptors (IP receptors); however, some of them can also activate the nuclear receptor peroxisome proliferator-activated receptor beta (PPARbeta). We examined the possibility that PPARbeta is a therapeutic target for the treatment of pulmonary hypertension. Using the newly approved (for pulmonary hypertension) prostacyclin mimetic treprostinil sodium, reporter gene assays for PPARbeta activation and measurement of lung fibroblast proliferation were analyzed. Treprostinil sodium was found to activate PPARbeta in reporter gene assays and to inhibit proliferation of human lung fibroblasts at concentrations consistent with an effect on PPARs but not on IP receptors. The effects of treprostinil sodium on human lung cell proliferation are mimicked by those of the highly selective PPARbeta ligand GW0742. There are no receptor antagonists for PPARbeta or for IP receptors, but by using lung fibroblasts cultured from mice lacking PPARbeta (PPARbeta-/-) or IP (IP-/-), we demonstrate that the antiproliferative effects of treprostinil sodium are mediated by PPARbeta and not IP in lung fibroblasts. These observations suggest that some of the local, longer-term benefits of treprostinil sodium on reducing the remodeling associated with pulmonary hypertension may be mediated by PPARbeta. This study is the first to identify PPARbeta as a potential therapeutic target for the treatment of pulmonary hypertension, which is important because orally active PPARbeta ligands have been developed for the treatment of dyslipidemia.

Current situation of Chagas disease in Central America

Chagas disease in Central America is known since 1913 when the first human case was reported in El Salvador. The other Central American countries reported their first cases between 1933 and 1967. On October 1997 was launched the Central American Initiative for Chagas Disease Control (IPCA). The objectives of this sub-regional Initiative are: (1) the elimination of Rhodnius prolixus in Central America; (2) the reduction of the domiciliary infestation of Triatoma dimidiata; and (3) the elimination of the transfusion transmission of Trypanosoma cruzi. Significant advancements being close to the elimination of R. prolixus in Central America and the control of the transfusion transmission has been a transcendent achievement for the sub-region. The main challenges that the IPCA will have in the close future are: developing effective strategies for control and surveillance of T. dimidiata; and surveillance of other emerging triatominae species like R. pallescens, T. nitida, and T. ryckmani.

The ghost of social environments past: dominance relationships include current interactions and experience carried over from previous groups.

Dominance hierarchies pervade animal societies. Within a static social environment, in which group size and composition are unchanged, an individual's hierarchy rank results from intrinsic (e.g. body size) and extrinsic (e.g. previous experiences) factors. Little is known, however, about how dominance relationships are formed and maintained when group size and composition are dynamic. Using a fusion-fission protocol, we fused groups of previously isolated shore crabs (Carcinus maenas) into larger groups, and then restored groups to their original size and composition. Pre-fusion hierarchies formed independently of individuals' sizes, and were maintained within a static group via winner/loser effects. Post-fusion hierarchies differed from pre-fusion ones; losing fights during fusion led to a decline in an individual's rank between pre- and post-fusion conditions, while spending time being aggressive during fusion led to an improvement in rank. In post-fusion tanks, larger individuals achieved better ranks than smaller individuals. In conclusion, dominance hierarchies in crabs represent a complex combination of intrinsic and extrinsic factors, in which experiences from previous groups can carry over to affect current competitive interactions.

Aedes aegypti, Aedes albopictus, and dengue in Argentina: current knowledge and future directions

Since the reinfestation of South American countries by Ae. aegypti, dengue fever (DF) and dengue hemorrhagic fever (DHF) have become a major public health concern. The aim of this paper was to review the information related with Aedes vectors and dengue in Argentina since the reintroduction of Ae. aegypti in 1986. The geographic distribution of Ae. albopictus is restricted to the Northeast, and that of Ae. aegypti has expanded towards the South and the West in comparison with the records during the eradication campaign in the 1960s. Since 1998, 4,718 DF cases have been reported concentrated in the provinces of Salta, Formosa, Misiones, Jujuy and Corrientes. Despite the circulation of three dengue virus serotypes (DENV-1, -2 and -3) in the North of the country, DHF has not occurred until the present. The information published over the last two decades regarding mosquito abundance, temporal variations, habitat characteristics, competition, and chemical and biological control, was reviewed. Considering the available information, issues pending in Argentina are discussed. The presence of three DENV, the potential spread of Ae. albopictus, and the predicted climate change suggest that dengue situation will get worse in the region. Research efforts should be increased in the Northern provinces, where DHF is currently an actual risk.

Current profile of Mansonella ozzardi (Nematoda: Onchocercidae) in communities along the Ituxi river, Lábrea municipality, Amazonas, Brazil

The objective of this paper was to describe the current status of Mansonella ozzardi prevalence among the inhabitants of 12 communities along the Ituxi river, in Lábrea municipality, state of Amazonas. The prevalence of M. ozzardi was determined using thick blood smears obtained by digital punctures. M. ozzardi was found in 30.23% of the samples collected (39/129), with similar prevalence between genders (males: 30.30%; females: 30.16%); the highest prevalence was found in homemakers (45.45%) followed by farmers (38.77%). Among age groups, males and females older than 48 exhibited the highest rates. These results show a significative increase in the prevalence when compared to a epidemiological study made 26 years ago in the same area as well as a different epidemiological profile (gender and occupation) in relation to other areas in Amazonas.

Treating ocular toxoplasmosis: current evidence

The current treatment of ocular toxoplasmosis is controversial. The mainstay of treatment has been pyrimethamine and sulphonamides with or without systemic corticosteroids, but the actual evidence that antibiotics have a beneficial effect in recurrent toxoplasmic retinochoroiditis is unsupported by randomised placebo controlled trials. Thus far there have only been three studies looking at the efficacy of antibiotic treatment, all of which were methodologically weak and two of which were perfomed more than 30 years ago. All studies reported adverse effects from treatment. There is an urgent need for further randomised, double blind, placebo controlled studies for lesions in all parts of the retina and to test the efficacy of adjunctive corticosteroid treatment.

Current status of pediatric home enteral nutrition in Spain: the importance of the NEPAD register.

Home enteral nutrition (HEN) is a type of enteral nutrition (EN) which is becoming progressively more widespread in pediatrics due to the benefits it affords to patients, their families and to reducing hospital costs. However, the true extent of its use is unknown in Spain as the data-base set up for this purpose is still underused (Registro de Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria -NEPAD-). More thorough registration of patients in the NEPAD online register will provide information about the characteristics of HEN in Spain: prevalence, diagnosis, the population sector being administered HEN, complications and developments. Likewise, forecast and planning of the necessary resources could be made while those in use could be analysed.