Neuroendocrinología y conducta (II)

En este artículo se proporciona una revisión exhaustiva (en dos partes) de la investigación realizada en los 70 sobre andrógenos y conducta agresiva, tanto en animales como en humanos (1ª parte). Se propone que se adopte el modelo de la "Psicopatología de la Desinhibición" de Gorestein y Newman (1980) para el estudio de la personalidad agresiva y desinhibida caracterizada por la impulsividad y búsqueda de sensaciones novedosas entre la que es prototípica la psicopatía. Este modelo permite incluir la hipótesis aminérgica del rasgo de personalidad denominado "Búsqueda de sensaciones" que postula que los individuos desinhibidos tienen niveles bajos en la actividad MAO plaquetar, enzima que es inhibido por los estrogenos y andrógenos (2ªparte).

El rasgo de personalidad "Búsqueda de sensaciones": una teoría psicobiológica

En este trabajo se expone y se sintetiza la teoría del rasgo de personalidad denominado "búsqueda de sensaciones", se proporciona información cronológica de la investigación empírica realizada desde los años 60 hasta nuestros días. Se incide en los correlatos biológicos de este rasgo en particular Potenciales Evocados (PE), Monoaminoxidades Plaquetear (MAO), Reflejo Orienativo (RO) y hormonas sexuales como la Testosterona (T) y Estradiol (E2). Se sugiere que se avance en la investigación psicobiológica del rasgo en cuestión, esfuerzo que por otro lado está generando un importante soporte empírico a la teoría.

Psicopatología de la desinhibición: un modelo para el estudio de la psicopatía

En este artículo se hace referencia a un modelo analógico para el estudio de los síndromes de la conducta desinhibida en humanos, denominado "Psicopatología de la Desinhibición". Este modelo propone una similitud entre las manifestaciones de conducta de humanos desinhibidos y los animales con lesión septal, sugiriendo de forma hipotética qué irregularidades en el sistema límbico podrían ser el sustrato biológico de estos síndromes entre los que es prototípico la psicopatología.

Comment on reversal of hypogonadotropic hypogonadism in a Chinese cohort.

The reversal of congenital hypogonadotropic hypogonadism (CHH) is a relatively recent phenomenon that has gained increasing attention over the past 10 years. Yet to date, only one prospective study has been conducted estimating that 10% (95% confidence interval [CI]: 2%-18%) of cases undergo reversal. [1] Other retrospective studies have reported rates in the range of 5%-8% [2],[3] and a recent study showed 44/308 (14%, 95% CI: 11%-19%) CHH patients underwent reversal. [4] Moreover, a time-to-event analysis in this large cohort revealed a lifetime reversal incidence of 22%. The article by Mao and colleagues presented in this issue is a meaningful contribution to our understanding of reversal as it examines the largest retrospective cohort to date. [5] Interestingly, they report the rate of reversal as 5% (95% CI: 3%-8%) in this Chinese cohort. It is difficult to reconcile the discrepancies in rates of reversibility and direct comparisons are hampered by the variable definitions employed. Using a novel definition for reversal (i.e, either endogenous testosterone (T) >270 ng dl−1 , serum T gradually increasing above 150 ng dl−1 with increased testicular volume, or normal spontaneous sperm production/normal erectile function/ejaculation), Mao and colleagues posit that testicular size and triptorelin-stimulated LH levels are reliable predictive factors for reversal. However, these cannot be considered as hard and fast rules for predicting reversal as the groups intersect - akin to the overlap observed between CHH patients and those with delayed puberty. Indeed, the fact that approximately half (44%, 95% CI: 25%-66%) of the reversal patients in the study by Mao et al.[5] were diagnosed between 17 and 19 years of age, underscores the challenge in differentiating CHH from extreme normal variants of puberty. This study further lends credence the recently reported observations that reversals may relapse. [4],[6] The notion that reversal may not be lasting highlights the vulnerability of the reproductive axis among CHH patients. While the mechanism(s) for relapse are unclear, it seems plausible that environmental, metabolic or psychiatric stressors could contribute. The factors that Mao and colleagues identify as significantly different in cases of reversal, were not informative for identifying those cases that relapsed back to a hypogonadal state. Notably, reversal has been reported in probands harboring mutations in genes underlying CHH. [1],[3],[4],[6] Unfortunately, comprehensive genetic screening on the Chinese cohort is not available. The reversal phenomenon is fascinating for its glimpse into the plasticity of the neuroendocrine control of reproduction. Future directions will almost certainly include investigation of specific genetic signatures and novel biomarkers for predicting reversal (and relapse). Yet CHH is a rare condition and to fully elucidate the biology of reversible CHH, it will be important to harmonize definitions of what constitutes a reversal, carefully phenotype patients and chart the natural history of their CHH. In this way, this unique human disease model may offer further insights into the control of human reproduction and provide opportunities to translate discoveries into enhanced approaches to improve the care and quality of life for these patients.

Emprego de catalisadores à base de níquel para homo- e copolimerização de estireno

This review deals with the homo- and copolymerization of styrene with nickel catalysts. The catalytic activity, polymer stereoregularity, polymer molecular weight and polydispersity are dependent upon nickel ligands and reaction parameters. Catalysts supported on silica, treated with methylaluminoxane (MAO), have shown higher stereospecificity and activity compared to homogeneous ones. The influence of these parameters is discussed focusing on the elucidation of some aspects of the polymerization mechanism.

Catalisadores metalocênicos suportados para a produção de poliolefinas: revisão das estratégias de imobilização

The inadequacy of strategies used for the heterogeneization of metallocene catalysts is pointed out as one of the main causes of the lack of industrial employability of such polymerization catalysts. The main problems are the necessity of large quantity of MAO (cocatalyst) and the inability to control molecular mass distribution of the polymers. Based on this background, the main strategies for the heterogeneization of metallocenes are here reviewed. The advantages and disadvantages of each strategy are presented and discussed on theoretical and practical perspective. Considering the results reported on the different researches, outcomes of heterogeneization strategies are pointed out.

In situ synthesis of nanoclay filled polyethylene using polymer supported metallocene catalyst system

In situ ethylene polymerizations were performed using bis(cyclopentadiene)titanium dichloride supported on polyethersulfone as catalyst. The bis(cyclopentadiene)titanium dichloride supported on polyethersulfone catalyst activity estimated by ethylene polymerization was 360 kgPE/molTi/h. During polymerization the fillers used were montmorillionite nanoclays having surface modifications with 35-45 wt% dimethyl dialkyl(14-18)amine (FA) and 25-30 wt% trimethyl stearyl ammonium (FB). These fillers were pretreated with methylaluminoxine (MAO; cocatalyst) for better dispersion onto the polymer matrix. The formation of polyethylene within the whole matrix was confirmed by FTIR studies. It was found that the nature of nanofiller did not have any remarkable effect on the melting characteristics of the polymer. TGA study indicates that nanoclay FB filled polyethylene has higher thermal stability than nanoclay FA filled polyethylene. The melting temperature of the obtained polyethylenes was 142 ºC, which corresponds to that synthesized by the polyether sulfone supported catalyst.

Membrane emulsification in preparation of single site catalyst

In the theory part the membrane emulsification was studied. Emulsions are used in many industrial areas. Traditionally emulsions are prepared by using high shear in rotor-stator systems or in high pressure homogenizer systems. In membrane emulsification two immiscible liquids are mixed by pressuring one liquid through the membrane into the other liquid. With this technique energy could be saved, more homogeneous droplets could be formed and the amount of surfactant could be decreased. Ziegler-Natta and single-site catalysts are used in olefin polymerization processes. Nowadays, these catalysts are prepared according to traditional mixing emulsification. More homogeneous catalyst particles that have narrower particle size distribution might be prepared with membrane emulsification. The aim of the experimental part was to examine the possibility to prepare single site polypropylene catalyst using membrane emulsification technique. Different membrane materials and solidification techniques of the emulsion were examined. Also the toluene-PFC phase diagram was successfully measured during this thesis work. This phase diagram was used for process optimization. The polytetrafluoroethylene membranes had the largest contact angles with toluene and also the biggest difference between the contact angles measured with PFC and toluene. Despite of the contact angle measurement results no significant difference was noticed between particles prepared using PTFE membrane or metal sinter. The particle size distributions of catalyst prepared in these tests were quite wide. This would probably be fixed by using a membrane with a more homogeneous pore size distribution. It is also possible that the solidification rate has an effect on the particle sizes and particle morphology. When polymeric membranes are compared PTFE is probably still the best material for the process as it had the best chemical durability.

Uusia tulkintoja maailmanhistorian pahimmasta nälänhädästä

Kirjallisuusarvostelu

Iso-Britannia vastakumouksellisessa sodassa : turvallisuusjoukkojen käyttöperiaatteet Malaijalla (1948-1960) ja Keniassa (1952-1960)

Toisen maailmansodan jälkeisenä ajanjaksona Iso-Britannia joutui useisiin vastakumouksellisen sodankäynnin konflikteihin siirtomaarakenteiden purkautumisen ja maailmanpoliittisen tilanteen johdosta. Tutkielma käsittelee Ison-Britannian turvallisuusjoukkojen käyttöperiaatteita vastakumouksellisen sodankäynnin konflikteissa Malaijalla vuosina 1948–1960 ja Keniassa vuosina 1952–1960. Tutkimus on luonteeltaan kvalitatiivinen tutkimus. Tutkimusmenetelmänä on käytetty lähdeaineistoon perustuvaa sisällönanalyysia. Lähdeaineisto koostuu pääsääntöisesti ulkomaalaisissa sotakouluissa tehdyistä opinnäytetöistä sekä tutkimus- ja aikalaiskirjallisuudesta. Lisäksi lähteenä on käytetty Britannian asevoimien ohjesääntöjä vastakumouksellisesta sodankäynnistä. Britannian vastakumouksellisen sodankäynnin taisteluoppi korosti sodan poliittista ratkaisua. Toisen maailmansodan jälkeisessä taisteluopissa uhkamalli muodostui Mao Tse-Tungin oppien mukaisesti taistelevasta kumouksellisesta liikkeestä. Malaijalla ja Keniassa kumouksellisen toiminnan raamit olivat monin osin yhtenäiset. Kapinalliset pystyttiin määrittämään selväksi vähemmistöryhmittymäksi koko kansakunnan osalta. Kapinallisten toiminta- aluetta olivat pääsääntöisesti maiden rajojen sisäpuolelle rajoittuvat harvaan asutut viidakko- ja metsäalueet. Britannian turvallisuusjoukkojen toiminnan perustana ollut ohjesääntö määritteli turvallisuusjoukkojen tärkeimmäksi tehtäväksi kumouksellisten eristämisen väestöstä, minkä avulla kumouksellisilta riistettiin toimintansa kannalta elintärkeät resurssit. Poliisivoimilla sekä paikallisesta väestöstä perustetuilla kodinturvajoukoilla kontrolloitiin ja valvottiin asuttuja alueita sotilasvoimien suorittaessa operaatioita viidakko- ja metsäalueiden laitamilla ja syvyydessä. Samanaikaisesti toteutetut uudelleenasuttamisen ohjelmat ja elintarvikkeiden säätelyt vaikeuttivat kapinallisten tukeutumista väestöön ja pakottivat heidät vetäytymään syrjäseuduille. Tutkielman tärkeimpänä havaintona voidaan pitää turvallisuusjoukkojen käyttöperiaatteiden yhtäläisyyttä Malaijalla ja Keniassa. Turvallisuusjoukkojen rakenne ja periaatteellinen käyttö noudattivat molemmissa konflikteissa samaa kaavaa perustuen Malaijan alkuvuosien havaintojen pohjalta laadittuun käsikirjaan. Turvallisuusjoukkojen käyttöön vaikuttaneet asteittaiset toimenpiteet kapinallisten eristämiseksi väestöstä, johtaen aina heidän voimiensa lopulliseen tuhoamiseen, olivat käyttöperiaatteiden kannalta ohjaava tekijä. Konflikteista saatujen havaintojen perusteella pystyttiin määrittelemään turvallisuusjoukkojen toimijoille selkeät roolit ja tehtäväkentät kriisien eri vaiheissa.

Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression

Curcumin, a major yellow pigment and active component of turmeric, has multiple anti-cancer properties. However, its molecular targets and mechanisms of action on human colon adenocarcinoma cells are unknown. In the present study, we examined the effects of curcumin on the proliferation of human colon adenocarcinoma HT-29 cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method and confirmed the curcumin-induced apoptosis by morphology and DNA ladder formation. At the same time, p53, phospho-p53 (Ser15), and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, pro-caspase-3, and pro-caspase-9 were determined by Western blot analysis. The colon adenocarcinoma cells were treated with curcumin (0-75 µM) for 0-24 h. We observed that p53 was highly expressed in HT-29 cells and curcumin could up-regulate the serine phosphorylation of p53 in a time- and concentration-dependent manner. An increase in expression of the pro-apoptotic factor Bax and a decrease in expression of the anti-apoptotic factor Bcl-2 were also observed in a time-dependent manner after exposure of 50 µM curcumin, while the expression of the anti-apoptotic factor Bcl-xL was unchanged. Curcumin could also down-regulate the expression of pro-caspase-3 and pro-caspase-9 in a time-dependent manner. These data suggest a possible underlying molecular mechanism whereby curcumin could induce the apoptosis signaling pathway in human HT-29 colon adenocarcinoma cells by p53 activation and by the regulation of apoptosis-related proteins. This property of curcumin suggests that it could have a possible therapeutic potential in colon adenocarcinoma patients.

TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

The tissue inhibitor of metalloproteinases (TIMP)-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs) but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line), L-02 (a normal liver cell line) and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma) using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13- and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60% and reduced the migration to about 30%. Meanwhile, our data showed that interleukin-6 (IL-6) (100 ng/mL) could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclin-dependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.

Development of fetal nicotine and muscarinic receptors in utero

The role of acetylcholine in the central and peripheral nervous systems is well established in adults. Cholinergic modulation of vascular functions and body fluid balance has been extensively studied. In the embryo-fetus, cholinergic receptors are widespread in the peripheral and central systems, including smooth muscle and the epithelial lining of the cardiovascular, digestive, and urinary systems, as well as in the brain. Fetal nicotine and muscarinic receptors develop in a pattern (e.g., amount and distribution) related to gestational periods. Cholinergic mechanisms have been found to be relatively intact and functional in the control of vascular homeostasis during fetal life in utero at least during the last third of gestation. This review focuses on the development of fetal nicotine and muscarinic receptors, and provides information indicating that central cholinergic systems are well developed in the control of fetal blood pressure and body fluid balance before birth. Therefore, the development of cholinergic systems in utero plays an important role in fetal vascular regulation, gastrointestinal motility, and urinary control.

Fetal development of regulatory mechanisms for body fluid homeostasis

The balance of body fluids is critical to health and the development of diseases. Although quite a few review papers have shown that several mechanisms, including hormonal and behavioral regulation, play an important role in body fluid homeostasis in adults, there is limited information on the development of regulatory mechanisms for fetal body fluid balance. Hormonal, renal, and behavioral control of body fluids function to some extent in utero. Hormonal mechanisms including the renin-angiotensin system, aldosterone, and vasopressin are involved in modifying fetal renal excretion, reabsorption of sodium and water, and regulation of vascular volume. In utero behavioral changes, such as fetal swallowing, have been suggested to be early functional development in response to dipsogens. Since diseases, such as hypertension, can be traced to fetal origin, it is important to understand the development of fetal regulatory mechanisms for body fluid homeostasis in this early stage of life. This review focuses on fetal hormonal, behavioral, and renal development related to regulation of body fluids in utero.