Central nervous system activity of a Tabernaemontana arborea alkaloid extract involves serotonergic and opioidergic neurotransmission in murine models.

Tabernaemontana arborea (Apocynaceae) is a Mexican tree species known to contain ibogan type alkaloids. This study aimed at determining central nervous system-related activities of an alkaloid extract obtained from the root bark of T. arborea. A gas chromatography-mass spectrometry (GC-MS) analysis was performed to describe the alkaloid profile of the extract. A wide dosing range (0.1 to 56.2 mg/kg) of this extract was evaluated in different murine models. Electrical brain activity was examined by electroencephalography (EEG). The extract's effects on motor coordination, ambulatory activity, and memory were analyzed based on the rotarod, open field (OFT), and object recognition tests (ORT), respectively. Antidepressant and antinociceptive activities were determined using the forced swimming test (FST) and the formalin assay, respectively. In order to elucidate the underlying mechanisms of action, the 5-HT1A receptor antagonist WAY100635 (1 mg/kg) or the opioid receptor antagonist naloxone (1 mg/kg) was included in the latter experiments. GC-MS analysis (µg/mg extract) confirmed the presence of the monoterpenoid indole alkaloids (MIAs) voacangine (207.00), ibogaine (106.33), vobasine (72.81), coronaridine (30.72), and ibogamine (24.2) as principal constituents of the extract, which exhibited dose- and receptor-dependent antidepressant (0.1 to 1 mg/kg; 5-HT1A) and antinociceptive (30 and 56.2 mg/kg; opioid) effects, without altering motor coordination, ambulatory activity, and memory. EEG indicated CNS depressant activity at high doses (30 and 56.2 mg/kg). The root bark of T. arborea contains a mixture of alkaloids that may hold therapeutic value in pain relief and the treatment of psychiatric diseases without causing neurotoxic activity at effective doses.

A synchrotron computed tomography dataset for validation of longitudinal tensile failure models based on fibre break and cluster development.

We performed in-situ tensile tests on two carbon fibre/epoxy composites with continuous scanning using synchrotron computed tomography (CT). Both composites were cross-ply laminates, and two specimens were tested for each composite. The voxel size was sufficiently small to recognize individual fibres and fibre breaks. For each test, 16-19 volumes were reconstructed, cropped down to the 0° plies and analysed to track fibre break and cluster development. This dataset provides the last CT volume before failure for each of the four specimens as well as the individual fibre break locations in all reconstructed volumes. These data are then plotted against predictions from six state-of-the-art strength models. The target is that these data become a benchmark for the development of new models, inspiring researchers to set up refined experiments and develop improved models.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Diagnosis of Cognitive Impairment Compatible with Early Diagnosis of Alzheimer's Disease. A Bayesian Network Model based on the Analysis of Oral Definitions of Semantic Categories.

BACKGROUND: Early detection of Alzheimer's disease (AD) has become one of the principal focuses of research in medicine, particularly when the disease is incipient or even prodromic, because treatments are more effective in these stages. Lexical-semantic-conceptual deficit (LSCD) in the oral definitions of semantic categories for basic objects is an important early indicator in the evaluation of the cognitive state of patients. OBJECTIVES: The objective of this research is to define an economic procedure for cognitive impairment (CI) diagnosis, which may be associated with early stages of AD, by analysing cognitive alterations affecting declarative semantic memory. Because of its low cost, it could be used for routine clinical evaluations or screenings, leading to more expensive and selective tests that confirm or rule out the disease accurately. It should necessarily be an explanatory procedure, which would allow us to study the evolution of the disease in relation to CI, the irregularities in different semantic categories, and other neurodegenerative diseases. On the basis of these requirements, we hypothesise that Bayesian networks (BNs) are the most appropriate tool for this purpose. METHODS: We have developed a BN for CI diagnosis in mild and moderate AD patients by analysing the oral production of semantic features. The BN causal model represents LSCD in certain semantic categories, both of living things (dog, pine, and apple) and non-living things (chair, car, and trousers), as symptoms of CI. The model structure, the qualitative part of the model, uses domain knowledge obtained from psychology experts and epidemiological studies. Further, the model parameters, the quantitative part of the model, are learnt automatically from epidemiological studies and Peraita and Grasso's linguistic corpus of oral definitions. This corpus was prepared with an incidental sampling and included the analysis of the oral linguistic production of 81 participants (42 cognitively healthy elderly people and 39 mild and moderate AD patients) from Madrid region's hospitals. Experienced neurologists diagnosed these cases following the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)'s Alzheimer's criteria, performing, among other explorations and tests, a minimum neuropsychological exploration that included the Mini-Mental State Examination test. RESULTS: BN's classification performance is remarkable compared with other machine learning methods, achieving 91% accuracy and 94% precision in mild and moderate AD patients. Apart from this, the BN model facilitates the explanation of the reasoning process and the validation of the conclusions and allows the study of uncommon declarative semantic memory impairments. CONCLUSIONS: Our method is able to analyse LSCD in a wide set of semantic categories throughout the progression of CI, being a valuable first screening method in AD diagnosis in its early stages. Because of its low cost, it can be used for routine clinical evaluations or screenings to detect AD in its early stages. Besides, due to its knowledge-based structure, it can be easily extended to provide an explanation of the diagnosis and to the study of other neurodegenerative diseases. Further, this is a key advantage of BNs over other machine learning methods with similar performance: it is a recognisable and explanatory model that allows one to study irregularities in different semantic categories.

Melatonin in the thyroid gland: regulation by thyroid-stimulating hormone and role in thyroglobulin gene expression.

Melatonin is an indoleamine with multiple functions in both plant and animal species. In addition to data in literature describing many other important roles for melatonin, such as antioxidant, circadian rhythm controlling, anti-aging, antiproliferative or immunomodulatory activities, our group recently reported that thyroid C-cells synthesize melatonin and suggested a paracrine role for this molecule in the regulation of thyroid activity. To discern the role played by melatonin at thyroid level and its involvement in the hypothalamic-pituitary-thyroid axis, in the present study we have analyzed the effect of thyrotropin in the regulation of the enzymatic machinery for melatonin biosynthesis in C cells as well as the effect of melatonin in the regulation of thyroid hormone biosynthesis in thyrocytes. Our results show that the key enzymes for melatonin biosynthesis (AANAT and ASMT) are regulated by thyroid-stimulating hormone. Furthermore, exogenous melatonin increases thyroglobulin expression at mRNA and protein levels on cultured thyrocytes and this effect is not strictly mediated by the upregulation of TTF1 or, noteworthy, PAX8 transcription factors. The present data show that thyroid C-cells synthesize melatonin under thyroid-stimulating hormone control and, consistently with previous data, support the hypothesis of a paracrine role for C-cell-synthesised melatonin within the thyroid gland. Additionally, in the present study we show evidence for the involvement of melatonin in thyroid function by directly-regulating thyroglobulin gene expression in follicular cells.

Placenta percreta con invasión vesical: una causa infrecuente de hematuria en la embarazada / Placenta percreta with bladder invasion: an uncommon cause of hematuria during pregnancy

La placenta percreta con invasión de la vejiga es una entidad muy infrecuente que puede producir complicaciones muy graves para la embarazada. Aunque a menudo se diagnostica en el momento del parto, las técnicas de imagen son muy útiles para diagnosticarla precozmente, lo que resulta fundamental para la planificación quirúrgica y evitar complicaciones potencialmente mortales. Presentamos un caso de esta entidad, y realizamos un breve repaso bibliográfico, con énfasis en el papel de las técnicas de imagen. Se trata de una gestante con antecedente de cesárea previa, hematuria y dolor lumbar. Tras realizar una ecografía y una resonancia magnética, se sugirió el diagnóstico de placenta percreta con invasión vesical, que se confirmó quirúrgicamente (AU)

Placenta percreta with bladder invasion is a very uncommon condition that can lead to very severe complications in pregnant women. Although it is often diagnosed during delivery, imaging techniques are very useful for early diagnosis, which is fundamental for planning surgery and avoiding potentially lethal complications. We present the case of a woman with a history of cesarean section who presented with hematuria and low back pain. The diagnosis of placenta percreta with bladder invasion was suggested after ultrasonography and magnetic resonance imaging and was confirmed at surgery. We provide a brief review of the literature, emphasizing the role of imaging techniques (AU)

Melatonin and glucose metabolism: clinical relevance.

The role of melatonin in glucose homeostasis is an active area of investigation. There is a growing body of evidence suggesting a link between disturbances in melatonin production and impaired insulin, glucose, lipid metabolism, and antioxidant capacity. Furthermore, melatonin has been found to influence insulin secretion both in vivo and in vitro, and night-time melatonin levels are related to night-time insulin concentrations in patients with diabetes. In several recent studies, a single nucleotide polymorphism of the human melatonin receptor 1B has been described as being causally linked to an increased risk of developing type 2 diabetes. Taken together, these data suggest that endogenous as well as exogenous melatonin may play a role in diabetes and associated metabolic disturbances not only by regulating insulin secretion but also by providing protection against reactive oxygen species, considering pancreatic ß-cells are particularly susceptible to oxidative stress because they possess only low-antioxidative capacity.

[Placenta percreta with bladder invasion: an uncommon cause of hematuria during pregnancy]. / Placenta percreta con invasión vesical: una causa infrecuente de hematuria en la embarazada.

Placenta percreta with bladder invasion is a very uncommon condition that can lead to very severe complications in pregnant women. Although it is often diagnosed during delivery, imaging techniques are very useful for early diagnosis, which is fundamental for planning surgery and avoiding potentially lethal complications. We present the case of a woman with a history of cesarean section who presented with hematuria and low back pain. The diagnosis of placenta percreta with bladder invasion was suggested after ultrasonography and magnetic resonance imaging and was confirmed at surgery. We provide a brief review of the literature, emphasizing the role of imaging techniques.

Crop row detection in maize fields inspired on the human visual perception.

This paper proposes a new method, oriented to image real-time processing, for identifying crop rows in maize fields in the images. The vision system is designed to be installed onboard a mobile agricultural vehicle, that is, submitted to gyros, vibrations, and undesired movements. The images are captured under image perspective, being affected by the above undesired effects. The image processing consists of two main processes: image segmentation and crop row detection. The first one applies a threshold to separate green plants or pixels (crops and weeds) from the rest (soil, stones, and others). It is based on a fuzzy clustering process, which allows obtaining the threshold to be applied during the normal operation process. The crop row detection applies a method based on image perspective projection that searches for maximum accumulation of segmented green pixels along straight alignments. They determine the expected crop lines in the images. The method is robust enough to work under the above-mentioned undesired effects. It is favorably compared against the well-tested Hough transformation for line detection.

Melatonin, a natural programmed cell death inducer in cancer.

Melatonin, an indolamine derived from the amino-acid tryptophan, participates in diverse physiological functions and has great functional versatility related to the regulation of circadian rhythms and seasonal behaviour, sexual development, retinal physiology, tumour inhibition, as an antioxidant, immunomodulatory and anti-aging properties. In relation to its oncostatic properties, there is evidence that tumor initiation, promotion or progression may be restrained by the night-time physiological surge of melatonin in the blood or extracellular fluid. In addition, depressed nocturnal melatonin concentrations or nocturnal excretion of the main melatonin metabolite, 6-sulfatoxymelatonin, were found in individuals with various tumor types. In the majority of studies, melatonin was shown to inhibit development and/or growth of various experimental animal tumors and some human cell lines in vitro. Many tumors do not respond to drug treatment due to their resistance to undergo apoptosis thereby contributing to the development of cancer. Thus, given the importance of the apoptotic program in cancer treatment, the role of melatonin in influencing apoptosis in tumor cells attracted attention because it seems that it actually promotes apoptosis in most tumor cells, in contrast to the obvious inhibition of apoptotic processes in normal cells. Thus, this paper is also intended to provide to the reader an up-date of all the researches that have been carried out to date, which investigate the proapoptotic effects of melatonin in experimental preclinical models of cancer (in vitro and in vivo) and the underlying proposed action mechanism of this effects. If melatonin uniformly induces apoptosis in cancer cells, the findings could have important clinical implications to improve the quality of live while preventing the appearance of cancer.

CYFRA 21-1 as a tool for distant metastasis detection in lung cancer.

BACKGROUND: A study to analyse tumor markers (CEA, CA125, CA15.3, CA19.9, CYFRA 21-1, and NSE) for metastasis detection in lung cancer patients. METHODS: Serum tumor markers from 73 lung cancer patients were measured before they were diagnosed. After lung cancer diagnosis, tumor markers were analyzed for the detection of distant metastases. RESULTS: In NSCLC patients CYFRA 21-1 and NSE showed differences between stage IV and any of the other stages, p < 0.05. The accuracy for metastasis detection was AUC = 81.5 % for CYFRA 21-1 and AUC = 78.6 % for < 0.05) were independent predictors for metastasis presence. No tumor marker showed significant differences according to stages in SCLC patients. CONCLUSIONS: CYFRA 21-1 could be used as a screening tool for metastasis detection in lung cancer patients without symptoms of metastasis as well as CYFRA 21-1 and NSE in NSCLC patients.

Introduction of fibrinogen in the treatment of hemostatic disorders during orthotopic liver transplantation: implications in the use of allogenic blood.

BACKGROUND: Orthotopic liver transplantation (OLT) requires a large amount of blood-derived resources. The indications for their availability in the surgery area is based on empirical protocols. The implementation of point-of-care apparatuses gives rise to the detection of hemostatic alterations due to functional deficits of fibrinogen. METHODS: To monitor coagulation disorders and other biochemical parameters, we used thromboelastometry (ROTEM®) and a MovlLab® unit, respectively. We evaluated the stability and firmness of the clot based on fibrin (FibTem test). The measurements were performed during all of the liver transplant stages: baseline, anhepatic, and reperfusion. Fibrinogen (hemocompletan) was administered to achieve maximum clot firmness, based on patient weight and the existence of surgical bleeding. This pilot cohort of 20 transplant patients (group B) compared outcomes with the 59 patients from the previous year (group A). RESULTS: Haemocompletan was administered to 45% of the 20 patients. The ratio of red blood cell components per patient diminished from 8.4 to 3.9 (53% reduction) and, fresh frozen plasma from 5.6 to 1.9 (65% reduction). Transfusions of platelet concentrates decreased by 50% with a ratio of 1.5-0.7 per patient. Likewise, 20% of transplant patients received no transfusions of blood products compared with 3.5% in the previous period. CONCLUSION: The incorporation of fibrinogen into the treatment of hemostatic disorders in OLT leads to a reduced use of allogenic blood products. We observed reduced number of patients who received transfusions, while those who underwent transfusion did so to a lesser degree.

Influence of reduction in the elution times on HPLC glycohaemoglobin results.

OBJECTIVES: To compare HPLC methods with short and long elution times for HbA1c measurement in blood. METHODS: Comparison between G7-Tosoh (1.2 min); Bio-Rad-Variant-II-Turbo (1.3 min) and Arkray-HA-8160 (2.9 min). RESULTS: Passing-Bablok regression equations were: Y=0.17+0.96X; Y=-0.39+1.01X; Y=-0.40+1.0X and the means of the differences using Bland-Altman Plot were 0.02; -0.34; 0.32 for HA-8160/G7-Tosoh, HA-8160/Variant-II-Turbo and G7-Tosoh/Variant-II-Turbo, respectively. CONCLUSIONS: Faster elution methods had no problems on reproducibility of results obtained by slower elution methods.

Age-related changes in melatonin synthesis in rat extrapineal tissues.

In the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and anti-aging properties. The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3- and 12month-old rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age. Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging.

A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production.

Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE(2) in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay in PGE(2)-diminished IL-2 production. The decrease in IL-2 production after PGE(2) and/or luzindole administration correlated with downregulation in the nuclear receptor RORalpha. We also highlighted a role of cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE(2) in the RORalpha expression. Finally, a significant RORalpha downregulation was observed in T cells permanently transfected with inducible MT(1) antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORalpha expression, opening a new way to understand melatonin regulation in lymphocyte physiology.

Melatonin biosynthesis in the thymus of humans and rats.

Melatonin is an indoleamine widely distributed in the evolution that shows a great functional versatility, playing an important role as a transmitter of photoperiodic information and exhibiting antioxidant, oncostatic, anti-aging and immunomodulatory properties. In vertebrates, this molecule is produced by the pineal gland and other extrapineal sites. The present study was carried out to investigate the presence of melatonin in thymus and the possibility of an endogenous melatonin synthesis in this organ, in which T cells are matured. In this work, we demonstrate in humans and rats that thymus contains melatonin, expresses the mRNAs encoding N-acetyltransferase and hydroxyindol-O-methyltransferase, the two key enzymes of the melatonin synthesis, and has this biosynthetic machinery activated. In addition, rat thymocytes cultured for 24 h exhibited high levels of melatonin. The results presented here suggest that human and rat thymuses are able to synthesize melatonin, which could have intracrine, autocrine and paracrine functions.

Thyrotropin-releasing hormone receptor expression in thyroid follicular cells: a new paracrine role of C-cells?

Thyrotropin-releasing hormone (TRH) synthesized in the hypothalamus has the capability of inducing the release of thyroid-stimulating hormone (TSH) from the anterior pituitary, which in turn stimulates the production of thyroid hormones in the thyroid gland. Immunoreactivity for TRH and TRH-like peptides has been found in some tissues outside the nervous system, including thyroid. It has been demonstrated that thyroid C-cells express authentic TRH, affecting thyroid hormone secretion by follicular cells. Therefore, C-cells could have a paracrine role in thyroid homeostasis. If this hypothesis is true, follicular cells should express TRH receptors (TRH-Rs) for the paracrine modulation carried out by C-cells. In order to elucidate whether or not C-cell TRH production could act over follicular cells modulating thyroid function, we studied TRH-Rs expression in PC C13 follicular cells from rat thyroid, by means of immunofluorescence technique and RT-PCR analysis. We also investigated the possibility that C-cells present TRH-Rs for the autocrine control of its own TRH production. Our results showed consistent expression for both receptors, TRH-R1 and TRH-R2, in 6-23 C-cells, and only for TRH-R2 in PC C13 follicular cells. Our data provide new evidence for a novel intrathyroidal regulatory pathway of thyroid hormone secretion via paracrine/autocrine TRH signaling.