La Reforma Psiquiátrica en Andalucía. Cuatro décadas de transformaciones en los servicios públicos de salud mental / The Psychiatric Reform in Andalusia (Spain) Four Decades of Transformations in Public Mental Health Services

El artículo pretende presentar de manera resumida las características más destacadas del proceso de transformación de las estructuras públicas de atención a problemas de salud mental, iniciada oficialmente en Andalucía en junio de 1984, con la aprobación por el Parlamento de una ley específica sobre el tema. A lo largo de estos ya casi 40 años, la arcaica estructura de servicios que caracterizaba la asistencia psiquiátrica se ha transformado en una red compleja de base y orientación comunitaria, superadora de los Hospitales Psiquiátricos y con un sector sanitario integrado en el Sistema Sanitario Público y otro intersectorial dependiente de la Fundación pública FAISEM. El texto presenta las características previas, las líneas de trabajo desarrolladas y los principales resultados obtenidos, con una valoración positiva en relación con la situación de partida, pero también con importantes aspectos no adecuadamente resueltos y que necesitan desarrollos posteriores que, sin embargo, no se están abordando hoy por hoy. (AU)

The article aims to present in a summarized way the most outstanding characteristics of the process of transformation of public structures of attention to mental health problems, officially initiated in Andalusia in June 1984, with the approval by Parliament of law on the subject. Throughout these almost 40 years the archaic structure of services that characterized psychiatric care has been transformed into a complex network of community orientation, surpassing the Psychiatric Hospitals and with a health sector integrated into the Public Health System and another intersectoral dependent on the FAISEM public Foundation. The text presents the previous characteristics, the lines of work developed, and the main results obtained, with a positive assessment in relation to the initial situation, but also with important aspects not adequately resolved and that need subsequent developments that, however, are not being addressed today. (AU)

La Reforma Psiquiátrica en Andalucía. Cuatro décadas de transformaciones en los servicios públicos de salud mental / The Psychiatric Reform in Andalusia (Spain) Four Decades of Transformations in Public Mental Health Services

El artículo pretende presentar de manera resumida las características más destacadas del proceso de transformación de las estructuras públicas de atención a problemas de salud mental, iniciada oficialmente en Andalucía en junio de 1984, con la aprobación por el Parlamento de una ley específica sobre el tema. A lo largo de estos ya casi 40 años, la arcaica estructura de servicios que caracterizaba la asistencia psiquiátrica se ha transformado en una red compleja de base y orientación comunitaria, superadora de los Hospitales Psiquiátricos y con un sector sanitario integrado en el Sistema Sanitario Público y otro intersectorial dependiente de la Fundación pública FAISEM. El texto presenta las características previas, las líneas de trabajo desarrolladas y los principales resultados obtenidos, con una valoración positiva en relación con la situación de partida, pero también con importantes aspectos no adecuadamente resueltos y que necesitan desarrollos posteriores que, sin embargo, no se están abordando hoy por hoy. (AU)

The article aims to present in a summarized way the most outstanding characteristics of the process of transformation of public structures of attention to mental health problems, officially initiated in Andalusia in June 1984, with the approval by Parliament of law on the subject. Throughout these almost 40 years the archaic structure of services that characterized psychiatric care has been transformed into a complex network of community orientation, surpassing the Psychiatric Hospitals and with a health sector integrated into the Public Health System and another intersectoral dependent on the FAISEM public Foundation. The text presents the previous characteristics, the lines of work developed, and the main results obtained, with a positive assessment in relation to the initial situation, but also with important aspects not adequately resolved and that need subsequent developments that, however, are not being addressed today. (AU)

Mirando atrás para seguir avanzando. Una reflexión crítica sobre el pasado y el presente de la atención en salud mental (II) / Looking back to keep moving forwar (d. A critical reflection on the past and present of mental health care (II)

Este es el segundo de una serie de dos artículos que tratan de hacer una valoración crítica de los principales aspectos teóricos y técnicos relacionados con la atención en salud mental que se han desarrollado en las 6 o 7 últimas décadas, como alternativa a dos tipos de posiciones consideradas inadecuadas, la del reduccionismo biomédico imperante y la de algunas tendencias nuevamente “antipsiquiátricas”. En este segundo artículo se valoran algunos movimientos interesantes de estos últimos años y se plantean algunas conclusiones y perspectivas de futuro, tratando de situarse en una perspectiva crítica razonable desde el marco de la atención comunitaria en salud mental. Considerada esta como el paradigma tecnológico desde el que cabe dar cuenta de la complejidad de los problemas de salud mental y ayudar a resolverlos en una interacción no menos compleja entre profesionales y usuarios y usuarias

This is the second of two papers that seek to make a critical assessment of the main theoretical and technical aspects related to mental health care developed in the last six or seven decades, as an alternative to two types of positions considered inadequate; namely, that of the dominant biomedical reductionism and those of some new "antipsy-chiatric" tendencies. In this second paper some interesting movements from recent years are valued and some conclusions and prospects for the future are raised, trying to take a reasonable critical stance from the community mental health care framework. This latter one considered as the technological paradigm from which it is possible to take into account the complexity of mental health problems and to solve them in a no less complex interaction between professionals and users

Melatonin modulates mitophagy, innate immunity and circadian clocks in a model of viral-induced fulminant hepatic failure.

The haemorrhagic disease virus (RHDV) is a non-cultivable virus that promotes in rabbits an acute disease which accomplishes many characteristics of an animal model of fulminant hepatic failure (FHF). Beneficial effects of melatonin have been reported in RHDV-infected rabbits. This study investigated whether protection against viral-derived liver injury by melatonin is associated with modulation of mitophagy, innate immunity and clock signalling. Rabbits were experimentally infected with 2 × 104 haemagglutination units of a RHDV isolate and killed at 18, 24 and 30 hours after infection (hpi). Melatonin (20 mg/kg body weight ip) was administered at 0, 12 and 24 hpi. RHDV infection induced mitophagy, with the presence of a high number of mitophagosomes in hepatocytes and increased expression of mitophagy genes. Greater expression of main innate immune intermediaries and inflammasome components was also found in livers with RHDV-induced FHF. Both mitophagy and innate immunity activation was significantly hindered by melatonin. FHF induction also elicited an early dysregulation in clock signalling, and melatonin was able to prevent such circadian disruption. Our study discloses novel molecular routes contributing to RHDV-induced damage progression and supports the potential of melatonin as a promising therapeutic option in human FHF.

Intraocular lens explantation in Spain: indications and outcomes at a tertiary referral center from 2010 to 2018.

PURPOSE: To evaluate the causes of IOL explantation, techniques for secondary IOL implantation, visual outcomes and complications. METHODS: Setting: Department of Ophthalmology Complexo Hospitalario Universitario A Coruña, Spain. DESIGN: Retrospective study. All explanted IOLs from January 2010 to June 2018 were included. Medical records were reviewed to determine the surgical indication for IOL explantation, type of IOL implanted, time between surgeries, visual outcomes and surgical complications. RESULTS: One hundred forty-one IOLs were explanted (134 patients). Mean time from original surgery to IOL explantation was 7.89 ± 5.81 years. Causes of IOL explantation were IOL dislocation (81.56%)-in-the-bag IOL dislocation (71.63%), out-of-the-bag IOL dislocation (9.9%)-corneal decompensation (12.05%), refractive surprise (3.5%), uveitis-glaucoma-hyphema syndrome (1.4%), IOL opacification (1.4%). Procedures for secondary IOL implantation were retropupillar iris-claw IOL (63.8%), flanged scleral fixated IOL (9.2%), three-piece IOL in ciliary sulcus (8.5%), angle-supported anterior chamber IOL (7.1%), in-the-bag IOL (3.5%), scleral fixated IOL with sutures (0.7%). Ten cases (7.1%) were left aphakic. Mean preoperative and postoperative logMAR CDVA were 1.34 ± 0.87 and 0.63 ± 0.69, respectively (p = 0.000). Mean preoperative IOP and postoperative IOP were 16.78 ± 4.49 and 15.53 ± 3.476 mmHg, respectively (p = 0.005). Complications include cystoid macular edema (7.8%), glaucoma (7.1%), IOL luxation (2.1%), retinal detachment (1.4%), trophic ulcer and leucoma (1.4%), corneal decompensation (1.4%). CONCLUSIONS: In-the-bag IOL dislocation was the most frequent indication for IOL explantation, followed by pseudophakic bullous keratopathy. Simultaneous IOL exchange for a retropupillar iris-claw IOL was the most frequent procedure for secondary IOL implantation. Mean CDVA improved significantly and IOP decreased significantly after IOL explantation. The most frequent postoperative complication was cystoid macular edema.

Mirando atrás para seguir avanzando. Una reflexión crítica sobre el pasado y el presente de la atención en salud mental (I) / Looking back to keep moving forward. A critical reflection on the past and present of mental health care (I)

Este es el primero de una serie de dos artículos que tratan de hacer una valoración crítica de los principales aspectos teóricos y técnicos relacionados con la atención en salud mental que se han desarrollado en las 6 o 7 últimas décadas. Se intenta con ello situar los problemas de la atención en salud mental, y, dentro de ellos, los de la psiquiatría, por contraposición a dos tipos de posiciones consideradas inadecuadas: las del reduccionismo biomédico dominante y las de algunas tendencias "antipsiquiátricas", formalmente opuestas pero que, a mi entender, simplifican excesivamente la visión alternativa, con el riesgo de dejar de lado aspectos básicos de nuestras disciplinas y prácticas profesionales. En este primer artículo se hace una presentación general del conjunto, se exponen algunas posiciones filosóficas previas y se analizan críticamente distintos aspectos de la integración de la salud mental en el campo sanitario

This is the first of two papers that seek to make a critical assessment of the main theoretical and technical aspects related to mental health care developed in the last six or seven decades. It attempts to situate the problems of mental health care, and, within them, those of psychiatry, as opposed to two types of positions considered inadequate: the dominant biomedical reductionism and those of some new "antipsychiatric" tendencies, both of which, although formally opposite, oversimplify, in my opinion, the alternative vision, with the risk of leaving aside basic aspects of our disciplines and professional practices. In this first paper, a general overview is provided, some previous philosophical positions are reviewed, and some of the main implications of integrating mental health in the health field are critically analyzed

Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine-induced hepatocellular carcinoma.

Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight ip) once a week for 8 weeks. Melatonin was given at 5 or 10 mg kg-1 d-1 ip beginning 4 weeks after the onset of DEN administration and ending at the sacrifice time (10, 20, 30, or 40 weeks). Liver expression of Bmal1, Clock, Npas2, Rorα, and Sirt1 increased, whereas Cry1, Per1, Per2, Per3, CK1ε, Rev-erbα, and Rev-erbß decreased following DEN administration. Melatonin treatment prevented changes in the expression of clock genes, and this effect was accompanied by an upregulation of the MT1 receptor and reduced levels of the hypoxia-inducible factors Hif-1α and Hif-2α. An increased expression of p21, p53, and PARP1/2, a higher Bax/Bcl-2 ratio, and a lower expression of Cyclin D1, CDK6, HSP70, HSP90, and GRP78 proteins were also observed in melatonin-treated mice. Melatonin significantly potentiated the suppression of proliferation and cell cycle arrest induced by the synthetic REV-ERB agonist SR9009 in human Hep3B cells, and BMAL1 knocking down attenuated the pro-apoptotic and antiproliferative effect of melatonin. Results support a contribution of changes in the circadian clock components to the beneficial effects of melatonin in HCC and highlight the usefulness of strategies modulating the circadian machinery in hepatocarcinogenesis.

Rehabilitación psicosocial y atención comunitaria: algunas consideraciones críticas y una propuesta de guion para el debate / Psychosocial rehabilitation and community care: some critical considerations and a proposal of an outline for discussion

El artículo pretende situar de manera ordenada y sintética distintos aspectos que son objeto de debate profesional en relación con eso que llamamos rehabilitación. Debate que afecta también a nuestra Asociación (y especialmente a su sección de Rehabilitación) y que versa sobre si las distintas «cosas» que incluimos habitualmente bajo esa denominación genérica y supuestamente unitaria constituyen algo separado, diferenciado o integrado en la atención comunitaria, si son de carácter general o especializado, si deben adscribirse al sistema sanitario o a los servicios sociales o si pueden desarrollarse incluso fuera del ámbito estrictamente profesional. Para ello se analizan primero algunos de los factores que parecen condicionar el debate y se enumeran posteriormente los principales aspectos sobre los que versa, tratando de situar los temas lo más objetivamente posible, pero sin renunciar a manifestar explícitamente nuestras opiniones (AU)

This article intends to present in an ordered and synthetic way different aspects that are object of professional debate in relation to what we call rehabilitation. It’s a debate that also concerns our Association (and most specially its Rehabilitation section) and deals with the question whether the different «things» which we use to include under that generic and supposedly unitary denomination constitute something separated, differentiated or integrated in community care, whether they are of a general or specialized character, whether they must be assigned to the health or to the social services systems or whether it can even be developed outside the strictly professional system. With this goal we analyze some of the main factors involved in this debate, trying to situate the topics in an objective manner but without resigning to express our own opinions (AU)

Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells.

The sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) system is involved in different pathological processes, including fibrogenesis. Melatonin abrogates activation of hepatic stellate cells (HSCs) and attenuates different profibrogenic pathways in animal models of fibrosis, but it is unknown if protection associates with its inhibitory effect on the SphK1/S1P axis. Mice in treatment groups received carbon tetrachloride (CCl4 ) 5 µL g-1 body wt i.p. twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg kg-1  day-1 i.p, beginning 2 weeks after the start of CCl4 administration. At both 4 and 6 weeks following CCl4 treatment, liver mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased significantly. S1P production, and expression of S1P receptor (S1PR)1, S1PR3 and acid sphingomyelinase (ASMase) were significantly elevated. However, there was a decreased expression of S1PR2 and S1P lyase (S1PL). Melatonin attenuated liver fibrosis, as shown by a significant inhibition of the expression of α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-ß and collagen (Col) Ι. Furthermore, melatonin inhibited S1P production, lowered expression of SphK1, S1PR1, SP1R3, and ASMase, and increased expression of S1PL. Melatonin induced a reversal of activated human HSCs cell line LX2, as evidenced by a reduction in α-SMA, TGF-ß, and Col I expression. Melatonin-treated cells also exhibited an inhibition of the SphK1/S1P axis. Antifibrogenic effect of SphK1 inhibition was confirmed by treatment of LX2 cells with PF543. Abrogation of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in liver fibrogenesis. © 2016 BioFactors, 43(2):272-282, 2017.

Melatonin inhibits the sphingosine kinase 1/sphingosine-1-phosphate signaling pathway in rabbits with fulminant hepatitis of viral origin.

The sphingosine kinase (SphK)1/sphingosine-1-phosphate (S1P) pathway is involved in multiple biological processes, including liver diseases. This study investigate whether modulation of the SphK1/S1P system associates to the beneficial effects of melatonin in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received 20 mg/kg of melatonin at 0, 12, and 24 hr postinfection. Liver mRNA levels, protein concentration, and immunohistochemical labeling for SphK1 increased in RHDV-infected rabbits. S1P production and protein expression of the S1PR1 receptor were significantly elevated following RHDV infection. These effects were significantly reduced by melatonin. Rabbits also exhibited increased expression of toll-like receptor (TLR)4, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, nuclear factor-kappa B (NF-κB) p50 and p65 subunits, and phosphorylated inhibitor of kappa B (IκB)α. Melatonin administration significantly inhibited those changes and induced a decreased immunoreactivity for RHDV viral VP60 antigen in the liver. Results obtained indicate that the SphK1/S1P system activates in parallel to viral replication and the inflammatory process induced by the virus. Inhibition of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in this animal model of ALF, and supports the potential of melatonin as an antiviral agent.

La coordinación sociosanitaria en la atención a personas con trastornos mentales graves / The coordination between health and social services in the care of people with severe mental disorders

La coordinación entre servicios sanitarios y sociales es una necesidad central en la atención a un número creciente de personas afectadas por distintos tipos de problemas de salud. La evolución de los patrones demográficos y epidemiológicos en nuestras sociedades hacen cada vez más patente esa necesidad, por lo general no adecuadamente cubierta por nuestros sistemas de atención. Un sector donde esa necesidad es clave es el de la atención a personas con discapacidades derivadas de padecer trastornos mentales graves. Se trata de un sector que ha permanecido demasiado tiempo al margen de los sistemas generales de la atención sanitaria y social como resultado del estigma social y de las tradicionales instituciones asilares, en un círculo vicioso que hay que romper para poder identificar y dar respuesta a las necesidades de dichas personas. De hecho, los procesos de cambio hacia una atención comunitaria, con objetivos de recuperación y no de meros cuidados paliativos o marginadores, incorporan necesariamente esa coordinación como un pilar básico de una atención orientada a la inclusión social y la ciudadanía. Aunque sigue habiendo importantes carencias al respecto, especialmente en nuestro país. Sin embargo, hay experiencias de cambio que, como en Andalucía, marcan líneas de desarrollo de una estrategia de atención integrada, cuyos fundamentos y principales elementos que se presentan de manera resumida en este artículo

Coordination between health and social services is a key point in caring for an increasing number of people affected by different types of health problems. The change in demographic and epidemiological patterns in our societies evidences the need of this coordination, usually not covered by our care systems. A sector in which the coordination is particularly important is the care of people with disabilities related to the suffering from severe mental disorders. This is a field that has been too long on the sidelines of the general health and social care systems as a result of the social stigma and traditional psychiatric institutions, setting in motion a vicious circle that must be broken in order to identify and to respond to the needs of such persons. In fact, the processes of change towards community care, with targets for recovery and not mere palliative or marginalizing care, necessarily incorporate this coordination as a cornerstone strategy for social inclusion and citizenship. Although there are still significant gaps in this regard, especially in Spain. However, there are experiences of change, such as that of Andalusia, which set the tone for the development of a strategy for integrated care, whose foundations and main elements we try to summarize in the present article

[The coordination betwen health and social services in the care of people with severe mental disorders]. / La coordinación sociosanitaria en la atención a personas con trastornos mentales graves.

Coordination between health and social services is a key point in caring for an increasing number of people affected by different types of health problems. The change in demographic and epidemiological patterns in our societies evidences the need of this coordination, usually not covered by our care systems. A sector in which the coordination is particularly important is the care of people with disabilities related to the suffering from severe mental disorders. This is a field that has been too long on the sidelines of the general health and social care systems as a result of the social stigma and traditional psychiatric institutions, setting in motion a vicious circle that must be broken in order to identify and to respond to the needs of such persons. In fact, the processes of change towards community care, with targets for recovery and not mere palliative or marginalizing care, necessarily incorporate this coordination as a cornerstone strategy for social inclusion and citizenship. Although there are still significant gaps in this regard, especially in Spain. However, there are experiences of change, such as that of Andalusia, which set the tone for the development of a strategy for integrated care, whose foundations and main elements we try to summarize in the present article.

Autophagic response in the Rabbit Hemorrhagic Disease, an animal model of virally-induced fulminant hepatic failure.

The Rabbit Hemorrhagic Disease Virus (RHDV) induces a severe disease that fulfils many requirements of an animal model of fulminant hepatic failure. However, a better knowledge of molecular mechanisms contributing to liver damage is required, and it is unknown whether the RHDV induces liver autophagy and how it relates to apoptosis. In this study, we attempted to explore which signalling pathways were involved in the autophagic response induced by the RHDV and to characterize their role in the context of RHDV pathogenesis. Rabbits were infected with 2 × 104 hemmaglutination units of a RHDV isolate. The autophagic response was measured as presence of autophagic vesicles, LC3 staining, conversion of LC3-I to autophagosome-associated LC3-II and changes in expression of beclin-1, UVRAG, Atg5, Atg12, Atg16L1 and p62/SQSTM1. RHDV-triggered autophagy reached a maximum at 24 hours post-infection (hpi) and declined at 30 and 36 hpi. Phosphorylation of mTOR also augmented in early periods of infection and there was an increase in the expression of the endoplasmic reticulum chaperones BiP/GRP78, CHOP and GRP94. Apoptosis, measured as caspase-3 activity and expression of PARP-1, increased significantly at 30 and 36 hpi in parallel to the maximal expression of the RHDV capsid protein VP60. These data indicate that RHDV infection initiates a rapid autophagic response, perhaps in an attempt to protect liver, which associates to ER stress development and is independent from downregulation of the major autophagy suppressor mTOR. As the infection continues and the autophagic response declines, cells begin to exhibit apoptosis.

Melatonin modulates the autophagic response in acute liver failure induced by the rabbit hemorrhagic disease virus.

Autophagy is an important survival pathway and participates in the host response to infection. Beneficial effects of melatonin have been previously reported in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). This study was aimed to investigate whether melatonin protection against liver injury induced by the RHDV associates to modulation of autophagy. Rabbits were infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received 20 mg/kg melatonin at 0, 12, and 24 hr postinfection. RHDV induced autophagy, with increased expression of beclin-1, ubiquitin-like autophagy-related (Atg)5, Atg12, Atg16L1 and sequestrosome 1 (p62/SQSTM1), protein 1 light chain 3 (LC3) staining, and conversion of LC3-I to autophagosome-associated LC3-II. These effects reached a maximum at 24 hr postinfection, in parallel to extensive colocalization of LC3 and lysosome-associated membrane protein (LAMP)-1. The autophagic response induced by RHDV infection was significantly inhibited by melatonin administration. Melatonin treatment also resulted in decreased immunoreactivity for RHDV viral VP60 antigen and a significantly reduction in RHDV VP60 mRNA levels, oxidized to reduced glutathione ratio (GSSG/GSH), caspase-3 activity, and immunoglobulin-heavy-chain-binding protein (BiP) and CCAAT/enhancer-binding protein homologous protein (CHOP) expression. Results indicate that, in addition to its antioxidant and antiapoptotic effects, and the suppression of ER stress, melatonin induces a decrease in autophagy associated with RHDV infection and inhibits RHDV RNA replication. Results obtained reveal novel molecular pathways accounting for the protective effect of melatonin in this animal model of ALF.

Association between traumatic experiences and psychosis among incarcerated men.

The possible influence of traumatic experiences on subsequent manifestations of psychosis has been the subject of intense scientific debate in the last decade. Whereas some authors have found a clear association between trauma and psychosis, others have pointed out methodological deficiencies in the research or have found only weak associations. Others found no association between trauma and psychosis in exclusive samples of men and recommend the use of studies stratified by sex. This article uses the data from an epidemiological study of a random sample of 500 male inmates in two prisons in Andalusia (Spain) to analyze the association between psychosis and trauma. The inmates were diagnosed using The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interviews by teams of experienced clinicians. The results show a clear association between traumatic events and some functional psychosis or some psychosis, including induced psychoses. These associations resist the possible effect of confusing variables such as the origin of the inmates, educational level, or having an addictive disorder. We discuss the need to pay special attention to traumatic experiences such as witnessing extreme violence against others or participating in acts of violence, particularly in men. Our results are compatible with different theories that defend the association between trauma and psychosis.

Melatonin treatment reduces endoplasmic reticulum stress and modulates the unfolded protein response in rabbits with lethal fulminant hepatitis of viral origin.

Hepatocyte apoptosis plays an important role in the development of fulminant hepatic failure (FHF). The objective of this study was to investigate whether endoplasmic reticulum (ER) stress and unfolded protein response (UPR) inhibition is an underlying mechanism of melatonin anti-apoptotic effects in an animal model of FHF of viral origin induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received melatonin at two concentrations of 10 mg/kg and 20 mg/kg at 0 hr, 12 hr and 24 hr postinfection. RHDV infection induced increased expression of CCAAT/enhancer-binding protein homologous protein (CHOP), immunoglobulin heavy chain binding protein (BiP/GRP78), glucose-regulated protein 94 (GRP94), phospho-c-Jun N-terminal kinase (JNK) and caspase-12. These effects were attenuated by melatonin. Double immunofluorescence staining showed colocalization of CHOP and cleaved caspase-3 in liver sections of RHDV-infected rabbits, while immunostaining decreased markedly with melatonin treatment. RHDV infection resulted in significant increases in the mRNA levels of activating transcription factor 6 (ATF6), ATF4, inositol-requiring enzyme 1 (IRE1), spliced X-box binding protein-1 (XBP1s) and tumor necrosis factor receptor-associated factor 2 (TRAF2). Melatonin attenuated the extent of the changes. Data obtained provide evidence that in rabbits with experimental infection by RHDV, reduction in apoptotic liver damage by melatonin is associated with attenuation of ER stress through a modulation of the three arms of UPR signaling and further support a potential hepatoprotective role of melatonin in FHF.

Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis.

Antitumor and antiviral properties of the antimalaria drug artemisinin from Artemisia annua have been reported. Novel artemisinin derivatives (AD1-AD8) have been synthesized and evaluated using in vitro models of liver/colon cancer and viral hepatitis B and C. Cell viability assays after treating human cell lines from hepatoblastoma (HepG2), hepatocarcinoma (SK-HEP-1), and colon adenocarcinoma (LS174T) with AD1-AD8 for a short (6h) and long (72h) period revealed that AD5 combined low acute toxicity together with high antiproliferative effect (IC50=1-5µM). Since iron-mediated activation of peroxide bond is involved in artemisinin antimalarial activity, the effect of iron(II)-glycine sulfate (ferrosanol) and iron(III)-containing protoporphyrin IX (hemin) was investigated. Ferrosanol, but not hemin, enhanced antiproliferative activity of AD5 if the cells were preloaded with AD5, but not if both compouds were added together. Five derivatives (AD1>AD2>AD7>AD3>AD8) were able to inhibit the cytopathic effect of bovine viral diarrhoea virus (BVDV), a surrogate in vitro model of hepatitis C virus (HCV), used here to evaluate the anti-Flaviviridae activity. Moreover, AD1 and AD2 inhibited the release of BVDV-RNA to the culture medium. Co-treatment with hemin or ferrosanol resulted in enhanced anti-Flaviviridae activity of AD1. In HepG2 cells permanently infected with hepatitis B virus (HBV), AD1 and AD4, at non-toxic concentrations for the host cells were able to reduce the release of HBV-DNA to the medium. In conclusion, high pharmacological interest deserving further evaluation in animal models has been identified for novel artemisinin-related drugs potentially useful for the treatment of liver cancer and viral hepatitis B and C.

Impacto de la "Ley de promoción de la autonomía personal y atención a las personas en situación de dependencia" en las personas con trastorno mental grave / Impact of the "Law on promotion of personal autonomy and care for people dependent" in population with severe mental disorder

La Ley 39/2006, conocida como Ley de Dependencia, ha generado, desde su aprobación, desconfianza por estar enfocada a la atención a la dependencia, siendo la promoción de la autonomía personal un elemento apenas desarrollado y secundario (AU)

Law 39/2006, known as Dependence Law, has generated skepticism since its approval, for being focused on dependancy and barely promoting personal autonomy, treating it as a secondary issue (AU)