Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1–53.0)/(22.6–32.9), Portugal (39.0–74.4)/(21.4–38.9), Netherlands (40.6–66.3)/(25.3–38.8) and UK (37.5–62.4)/(23.3–34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2–12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8–19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.
Drylands are one of the most diverse yet highly vulnerable social–ecological systems on Earth. Water scarcity has contributed to high levels of heterogeneity, variability and unpredictability, which together have shaped the long coadaptative process of coupling humans and nature. Land degradation and desertification in drylands are some of the largest and most far-reaching global environmental and social change problems, and thus are a daunting challenge for science and society. In this study, we merged the Drylands Development Paradigm, Holling's adaptive cycle metaphor and resilience theory to assess the challenges and opportunities for livelihood development in the Amapola dryland social–ecological system (DSES), a small isolated village in the semi-arid region of Mexico. After 450 years of local social–ecological evolution, external drivers (neoliberal policies, change in land reform legislation) have become the most dominant force in livelihood development, at the cost of loss of natural and cultural capital and an increasingly dysfunctional landscape. Local DSESs have become increasingly coupled to dynamic larger-scale drivers. Hence, cross-scale connectedness feeds back on and transforms local self-sustaining subsistence farming conditions, causing loss of livelihood resilience and diversification in a globally changing world. Effective efforts to combat desertification and improve livelihood security in DSESs need to consider their cyclical rhythms. Hence, we advocate novel dryland stewardship strategies, which foster adaptive capacity, and continuous evaluation and social learning at all levels. Finally, we call for an effective, flexible and viable policy framework that enhances local biotic and cultural diversity of drylands to transform global drylands into a resilient biome in the context of global environmental and social change.
complex adaptive systems; Drylands Development Paradigm; livelihood diversification; resilience thinking
Studies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology. Some forms of cancer appear to be associated to certain alternative mRNA splice variants, but their role in the cancer development and outcome is unclear.
We examined AS profiles by means of whole genome exon expression microarrays (Affymetrix GeneChip 1.0) in ovarian tumors and ovarian cancer-derived cell lines, compared to healthy ovarian tissue. Alternatively spliced genes expressed predominantly in ovarian tumors and cell lines were confirmed by RT-PCR.
Among several significantly overexpressed AS genes in malignant ovarian tumors and ovarian cancer cell lines, the most significant one was that of the zinc finger protein ZNF695, with two previously unknown mRNA splice variants identified in ovarian tumors and cell lines. The identity of ZNF695 AS variants was confirmed by cloning and sequencing of the amplicons obtained from ovarian cancer tissue and cell lines.
Alternative ZNF695 mRNA splicing could be a marker of ovarian cancer with possible implications on its pathogenesis.
Ovarian cancer; Alternative mRNA splicing; ZNF695
Data on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited.
Ours was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT) or standard triple therapy (LPV/r-ART) for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL). Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI) was determined and also a global deficit score (GDS) for study comparisons.
Seventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4%) patients on LPV/r-MT and 16 (94.1%) on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601). NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494). Mean (SD) GDS was 0.22 (0.20) in patients on LPV/r-MT and 0.47 (0.34) in those on LPV/r-ART (p = 0.012).
Suppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning.
It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT2A and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and behavioral function of these two receptors in mice. Prenatal stress increased 5-HT2A and decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition and mood. This pattern of expression of 5-HT2A and mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT2A agonist DOI, and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not due to effects of prenatal stress on maternal care. Additionally, a similar pattern of biochemical and behavioral changes were observed in mice born to mothers injected with poly-(I:C) during pregnancy as a model of prenatal immune activation. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for schizophrenia and other psychiatric disorders.
Although epidemiologic and socioeconomic criteria and biomedical risk factors indicate high-priority for tuberculosis (TB) control in Mexico, molecular epidemiology studies of the disease in the country are scarce.
Complete sociodemographic and clinical data were obtained from 248 of the 432 pulmonary TB (PTB) cases confirmed from 2006 to 2010 on the population under epidemiological surveillance in the state of San Luis Potosí, México. From most PTB cases with complete data Mycobacterium tuberculosis complex (MTC) isolates were recovered and their spoligotypes, lineages and families, geographic distribution and drug resistance determined.
Pulmonary tuberculosis incidence ranged from 2.4 to 33.4 (cases per 100,000 inhabitants) in the six state sanitary jurisdictions that were grouped in regions of low (jurisdictions I-II-III), intermediate (jurisdictions IV-V) and high incidence (jurisdiction VI) with 6.2, 17.3 and 33.4 rates, respectively. Most patients were poor, 50-years-median-age males and housewives. Among the 237 MTC spoligotyped isolates, 232 corresponded to M. tuberculosis (104 spoligotypes in 24 clusters) and five to M. bovis. The predominant Euro-American lineage was distributed all over the state, the East-Asian lineage (Beijing family) in the capital city, the Indo-Oceanic (Manila family) in eastern localities, and M. bovis in rural localities.
In San Luis Potosí TB affects mainly poor male adults and is caused by M. tuberculosis and to a minor extent by M. bovis. There is great genotypic diversity among M. tuberculosis strains, the Euro-American lineage being much more prevalent than the Indo-Oceanic and East-Asian lineages. The frequency of resistant strains is relatively low and not associated to any particular lineage.
Tuberculosis; Mycobacterium bovis; Spoligotypes; Molecular epidemiology; San Luis Potosí; Mexico; Social determinants of tuberculosis
Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown. Here we show that chronic atypical antipsychotics down-regulate the expression of mGlu2, an effect that is associated with decreased histone acetylation at its promoter in mouse and human frontal cortex. This epigenetic change occurs in concert with a 5-HT2A receptor-dependent up-regulation and increased binding of HDAC2 to the mGlu2 promoter. Viral-mediated over-expression of HDAC2 in frontal cortex decreases mGlu2 transcription and its electrophysiological properties, thereby increasing psychosis-like behavior. Conversely, HDAC inhibitors prevent the repressive histone modifications induced at the mGlu2 promoter by atypical antipsychotics, and augment their therapeutic-like effects. These observations support the view of HDAC2 as a promising new target to improve schizophrenia treatment.
In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity.
This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis.
Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed.
Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day).
Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects.
Schizophrenia; Hallucinogenic drugs; LSD; Mouse models; GPCR
G protein-coupled receptors form hetero-dimers and higher order hetero-oligomers, yet the significance of receptor heteromerization in cellular and behavioral responses is poorly understood. Atypical antipsychotic drugs, such as clozapine and risperidone all have in common a high affinity for the serotonin 5-HT2A receptor (2AR). However, closely related nonantipsychotic drugs, such as ritanserin and methysergide, while blocking 2AR function, lack comparable neuropsychological effects. Why some but not all drugs that inhibit 2AR-dependent signaling exhibit antipsychotic properties remains unresolved. We found that a heteromeric complex formed between the metabotropic glutamate 2 receptor (mGluR2) and the 2AR critically integrates the action of drugs affecting signaling and behavioral outcomes. Acting through the mGluR2/2AR heterocomplex, both glutamatergic and serotonergic drugs achieve a balance between Gi- and Gq-dependent signaling that predicts their psychoactive behavioral effects. These observations provide a novel mechanistic insight into antipsychotic action that may advance therapeutic strategies for schizophrenia.
Overexpression of type I interferon (IFN-I)-induced genes is a common feature of systemic lupus erythematosus (SLE) and its experimental models, but the participation of endogenous overproduction of IFN-I on it is not clear. To explore the possibility that abnormally increased IFN-I receptor (IFNAR) signaling could participate in IFN-I-induced gene overexpression of SLE, we examined the phosphorylation status of the IFNAR-associated signaling partners Jak1 and STAT2, and its relation with expression of its physiologic inhibitor SOCS1 and with plasma levels of IFNα and IFN-like activity.
Peripheral blood mononuclear cells (PBMC) from SLE patients with or without disease activity and healthy controls cultured in the presence or in the absence of IFNβ were examined by immunoprecipitation and/or western blotting for expression of the two IFNAR chains, Jak1, Tyk2, and STAT2 and their phosphorylated forms. In SLE but not in healthy control PBMC, Jak1 and STAT2 were constitutively phosphorylated, even in the absence of disease activity (basal pJak1: controls vs. active SLE p<0.0001 and controls vs. inactive SLE p = 0.0006; basal pSTAT2: controls vs. active and inactive SLE p<0.0001). Although SOCS1 protein was slightly but significantly decreased in SLE in the absence or in the presence of IFNβ (p = 0.0096 to p<0.0001), in SOCS1 mRNA levels were markedly decreased (p = 0.036 to p<0.0001). IFNβ induced higher levels of the IFN-I-dependent MxA protein mRNA in SLE than in healthy controls, whereas the opposite was observed for SOCS1. Although there was no relation to increased serum IFNα, active SLE plasma could induce expression of IFN-dependent genes by normal PBMC.
These findings suggest that in some SLE patients IFN-I dependent gene expression could be the result of a low IFNAR signaling threshold.
Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [3H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens.
Hallucinogenic drugs; LSD; Serotonin 5-HT2A receptor; Metabotropic glutamate mGlu2 receptor; G protein-coupled receptor (GPCR); Schizophrenia and psychosis
It has been hypothesized that exposure to heavy metals may impair male reproduction. To measure the effect produced by low doses of heavy metals on semen parameters, it is necessary to clarify in which body fluids those measurements must be performed. Sixty-one men attending infertility clinics participated in our study. Concentrations of lead, cadmium, and mercury were measured in whole blood, blood plasma, and seminal plasma using spectroanalytical and electrochemical methods. Semen analyses were performed according to World Health Organization criteria. For statistical analysis, Spearman's rank correlations, mean comparison tests, and discriminant analysis were calculated. Significant correlations between the measured concentrations of the three heavy metals in the same biological fluids were observed. However, no similar relationship was seen when comparing the concentrations in different body fluids of the same metal. According to our results and previous publications, seminal plasma might be the best body fluid for assessing impairment of human semen parameters.
Nowadays society is demanding more and more smart healthcare services that allow monitoring patient status in a non-invasive way, anywhere and anytime. Thus, healthcare applications are currently facing important challenges guided by the u-health (ubiquitous health) and p-health (pervasive health) paradigms. New emerging technologies can be combined with other widely deployed ones to develop such next-generation healthcare systems. The main objective of this paper is to review and provide more details on the work presented in “LOBIN: E-Textile and Wireless-Sensor-Network-Based Platform for Healthcare Monitoring in Future Hospital Environments”, published in the IEEE Transactions on Information Technology in Biomedicine, as well as to extend and update the comparison with other similar systems. As a result, the paper discusses the main advantages and disadvantages of using different architectures and communications technologies to develop wearable systems for pervasive healthcare applications.
Wearable Health Monitoring Systems (WHMS); Body Area Networks (BAN); Wireless Sensor Networks (WSN); ubiquitous health; pervasive health; e-Textile; indoor location
Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT2A receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu2/3 agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT2A and mGlu2 receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT2A receptor is up-regulated and the mGlu2 receptor is down-regulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT2A receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos, egr-1 and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia.
Schizophrenia; maternal influenza virus infection; G protein-coupled receptors (GPCR); serotonin 5-HT2A receptor; metabotropic glutamate receptors; hallucinogenic drugs (LSD)
Neurocognitive impairment constitutes a core feature of bipolar illness. The main domains affected are verbal memory, attention, and executive functions. Deficits in these areas as well as difficulties to get functional remission seem to be increased associated with illness progression. Several studies have found a strong relationship between neurocognitive impairment and low functioning in bipolar disorder, as previously reported in other illnesses such as schizophrenia. Cognitive remediation strategies, adapted from work conducted with traumatic brain injury patients and applied to patients with schizophrenia, also need to be adapted to individuals with bipolar disorders. Early intervention using functional remediation, involves neurocognitive techniques and training, but also psychoeducation on cognition-related issues and problem-solving within an ecological framework.
Neurocognition; functional remediation; bipolar disorder.
Because G protein-coupled receptors (GPCRs) are numerous, widely expressed and involved in major physiological responses, they represent a relevant therapeutic target for drug discovery, particularly regarding pharmacological treatments of neurological disorders. Among the biological phenomena regulating receptor function, GPCR heteromerization is an important emerging area of interest and investigation. There is increasing evidence showing that heteromerization contributes to the pharmacological heterogeneity of GPCRs by modulating receptor ontogeny, activation and recycling. Although in many cases the physiological relevance of receptor heteromerization has not been fully established, the unique pharmacological and functional properties of heteromers are likely to lead to new strategies in clinical medicine. This review describes the main GPCR heteromers and their implications for major neurological disorders such as Parkinson’s disease, schizophrenia and addiction. A better understanding of molecular mechanisms underlying drug interactions related to the targeting of receptor heteromers could provide more specific and efficient therapeutic agents for the treatment of brain diseases.
Heteromerization; heteromer; GPCR; neurological disorder; drug discovery
Animal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids.
The current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearman's rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day.
There were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium.
Our results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.
In this paper, we reported the butterflies and moths that are consumed in Mexico. We identified 67 species of Lepidoptera that are eaten principally in their larval stage in 17 states of Mexico. These species belong to 16 families: Arctiidae, Bombycidae, Castniidae, Cossidae, Geometridae, Hepialidae, Hesperiidae, Lasiocampidae, Noctuidae, Nymphalidae, Papilionidae, Pieridae, Pyralidae, Saturniidae, Sesiidae, and Sphingidae.
Saturniidae, Pieridae, Noctuidae and Nymphalidae were the more species consumed with 16, 11, 9, and 8 species, respectively.
The genera with the largest numbers of species were: Phassus, Phoebis, Hylesia and Spodoptera, with three species.
Their local distribution, corresponding to each state of Mexico, is also presented.
Little is known about raltegravir removal by hemodialysis in patients with end-stage renal disease (ESRD). We therefore measured raltegravir concentrations in plasma in pre- and postdialyzer blood samples from 2 ESRD HIV-infected patients. The hemodialysis extraction ratio and raltegravir hemodialysis clearance were 5.5% and 9.1 ml/min in patient 1 and 9.5% and 19.1 ml/min in patient 2, respectively. Our results suggest minimal raltegravir removal by hemodialysis with no specific raltegravir dosage adjustments required in HIV-infected patients undergoing hemodialysis.
ESA’s upcoming satellite Sentinel-2 will provide Earth images of high spatial, spectral and temporal resolution and aims to ensure continuity for Landsat and SPOT observations. In comparison to the latter sensors, Sentinel-2 incorporates three new spectral bands in the red-edge region, which are centered at 705, 740 and 783 nm. This study addresses the importance of these new bands for the retrieval and monitoring of two important biophysical parameters: green leaf area index (LAI) and chlorophyll content (Ch). With data from several ESA field campaigns over agricultural sites (SPARC, AgriSAR, CEFLES2) we have evaluated the efficacy of two empirical methods that specifically make use of the new Sentinel-2 bands. First, it was shown that LAI can be derived from a generic normalized difference index (NDI) using hyperspectral data, with 674 nm with 712 nm as best performing bands. These bands are positioned closely to the Sentinel-2 B4 (665 nm) and the new red-edge B5 (705 nm) band. The method has been applied to simulated Sentinel-2 data. The resulting green LAI map was validated against field data of various crop types, thereby spanning a LAI between 0 and 6, and yielded a RMSE of 0.6. Second, the recently developed “Normalized Area Over reflectance Curve” (NAOC), an index that derives Ch from hyperspectral data, was studied on its compatibility with simulated Sentinel-2 data. This index integrates the reflectance curve between 643 and 795 nm, thereby including the new Sentinel-2 bands in the red-edge region. We found that these new bands significantly improve the accuracy of Ch estimation. Both methods emphasize the importance of red-edge bands for operational estimation of biophysical parameters from Sentinel-2.
Sentinel-2; chlorophyll; LAI; NAOC; NDI; red-edge
Schizophrenia is one of the most common mental illnesses, with hereditary and environmental factors important for its etiology. All antipsychotics have in common a high affinity for monoaminergic receptors. Whereas hallucinations and delusions usually respond to typical (haloperidol-like) and atypical (clozapine-like) monoaminergic antipsychotics, their efficacy in improving negative symptoms and cognitive deficits remains inadequate. In addition, devastating side effects are a common characteristic of monoaminergic antipsychotics. Recent biochemical, preclinical and clinical findings support group II metabotropic glutamate receptors (mGluR2 and mGluR3) as a new approach to treat schizophrenia. This paper reviews the status of general knowledge of mGluR2 and mGluR3 in the psychopharmacology, genetics and neuropathology of schizophrenia
Schizophrenia; Antipsychotics; G protein-coupled receptors (GPCR); Serotonin receptors; 5-HT2A; Metabotropic glutamate receptors; mGluR2; mGluR3
To report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).
The present study was retrospective about non-randomized interventional case series. Fifty-one consecutive eyes with subfoveal (all types) CNV associated with AMD were treated by PDT and intravitreal (19.4±2.1)mg per 0.1mL TA at the Alicante Institute of Ophthalmology. The appearance of macular choriocapillaris and retinal pigment epithelium (RPE) atrophy was considered at two years follow-up. Thirty consecutive eyes treated by PDT alone, matched for age, sex, and type and size of CNV were considered as control group.
Twenty-one of 47 eyes in the study group (45%) and 7 of 30 eyes in the control group (23%) developed macular RPE and choriocapillaris atrophy in the treated area at month 24 (P=0.04, Chi-square test). The greatest diameter of the atrophic areas averaged (5044±1666)µm in the study group vs (4345±1550)µm in the control group. Mean final best corrected visual acuity (logarithm of minimal angle of resolution) was (0.87±0.33) in the cases with RPE atrophy vs (0.66±0.26) in the cases with no RPE atrophy in the study group (P=0.11, Mann-Whitney U test).
The association of high doses of intravitreal TA and PDT may increase the risk for RPE and choriocapillaris atrophy.
age related macular degeneration; choriocapillaris atrophy; intravitreous triamcinolone; photodynamic therapy; retinal pigment epithelium atrophy
Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs) on cognitive performance over time.
In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13) or novel antipsychotics (n = 26) at baseline and at two years after.
Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics.
Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.
Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation.
In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 ± 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 ± 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer' solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation and apoptosis were specifically determined in lung, bowel, and liver.
In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment.
Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage.
OBJECTIVES—The mechanisms behind the association between retinol-binding protein-4 (RBP4) and insulin resistance are not well understood. An interaction between iron and vitamin A status, of which RBP4 is a surrogate, has long been recognized. We hypothesized that iron-associated insulin resistance could be behind the impaired insulin action caused by RBP4.
RESEARCH DESIGN AND METHODS—Serum ferritin and RBP4 concentration and insulin resistance were evaluated in a sample of middle-aged men (n = 132) and in a replication independent study. Serum RBP4 was also studied before and after iron depletion in patients with type 2 diabetes. Finally, the effect of iron on RBP4 release was evaluated in vitro in adipose tissue.
RESULTS—A positive correlation between circulating RBP4 and log serum ferritin (r = 0.35 and r = 0.61, respectively; P < 0.0001) was observed in both independent studies. Serum RBP4 concentration was higher in men than women in parallel to increased ferritin levels. On multiple regression analyses to predict serum RBP4, log serum ferritin contributed significantly to RBP4 variance after controlling for BMI, age, and homeostasis model assessment value. Serum RBP4 concentration decreased after iron depletion in type 2 diabetic patients (percent mean difference −13.7 [95% CI −25.4 to −2.04]; P = 0.024). The iron donor lactoferrin led to increased dose-dependent adipose tissue release of RBP4 (2.4-fold, P = 0.005) and increased RBP4 expression, while apotransferrin and deferoxamine led to decreased RBP4 release.
CONCLUSIONS—The relationship between circulating RBP4 and iron stores, both cross-sectional and after iron depletion, and in vitro findings suggest that iron could play a role in the RBP4–insulin resistance relationship.