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1.
Medicine (Baltimore) ; 103(36): e39255, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252288

RESUMEN

The real-world outcomes of lonoctocog alfa (rVIII-SingleChain), a long-acting factor VIII (FVIII) with a favorable safety and efficacy profile in trials, were assessed in patients with hemophilia A in Iberian (Spain and Portugal). This was a retrospective study involving patients switching to rVIII-SingleChain from other FVIIIs in 7 Spanish and Portuguese hospitals. The efficacy and safety of replacement therapies were compared between 12 months before switching and the period from switching to the end of the study. Twenty-nine patients (median age 25 years; severe hemophilia A, 37.9%) were recruited. Before switching, 12 were on prophylaxis and were followed-up for a median of 12 months. After switching, 17 received prophylaxis with rVIII-SingleChain and were followed-up for a median of 41 months. Those with ≤2 weekly infusions increased from 37.5% before switching to 60.7% after switching to rVIII-SingleChain. The median monthly consumption was 312 IU/kg with prior FVIIIs and 273 IU/kg with rVII-SingleChain. Six spontaneous bleeds were reported in each period in the prophylaxis patients. In the entire cohort, 50 bleeds were reported with prior FVIIIs and 33 were reported after switching to rVIII-SingleChain. Patients requiring ≤1 dose for hemostasis increased from 44.0% with prior FVIIIs to 60.6% with rVIII-SingleChain. Responses were rated good/excellent in 95.4% of cases. No safety concerns were reported. Patients who switched to rVIII-SingleChain prophylaxis had excellent bleeding control and reduced infusion frequency in regular clinical practice, with the subsequent increase in quality-of-life.


Asunto(s)
Factor VIII , Hemofilia A , Humanos , Hemofilia A/tratamiento farmacológico , Estudios Retrospectivos , Adulto , Masculino , España , Factor VIII/uso terapéutico , Factor VIII/administración & dosificación , Adulto Joven , Portugal , Adolescente , Persona de Mediana Edad , Hemorragia , Resultado del Tratamiento , Niño , Sustitución de Medicamentos , Femenino
2.
J Psychiatry Neurosci ; 49(2): E96-E108, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38490646

RESUMEN

BACKGROUND: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. METHODS: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-ß precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. RESULTS: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. LIMITATIONS: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. CONCLUSION: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.


Asunto(s)
Enfermedad de Alzheimer , MicroARNs , Ratas , Masculino , Animales , Ratas Wistar , Autoestimulación/fisiología , Estreptozocina/toxicidad , Aprendizaje Espacial , Enfermedad de Alzheimer/terapia , Sirtuina 1/farmacología , Hipocampo , MicroARNs/genética , Aprendizaje por Laberinto
3.
Int J Mol Sci ; 24(14)2023 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-37511561

RESUMEN

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.


Asunto(s)
Micropartículas Derivadas de Células , Endometriosis , Femenino , Humanos , Endometriosis/patología , Etinilestradiol , Norpregnenos/metabolismo , Coagulación Sanguínea , Tromboplastina/metabolismo , Inflamación/metabolismo , Micropartículas Derivadas de Células/metabolismo
4.
Molecules ; 28(12)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37375240

RESUMEN

Coffee is one of the most consumed beverages in the world; its production is based mainly on varieties of the Coffea arabica species. Mexico stands out for its specialty and organic coffee. In Guerrero, the production is done by small indigenous community cooperatives that market their product as raw material. Official Mexico Standards stipulate the requirements for its commercialization within the national territory. In this work, the physical, chemical, and biological characterizations of green, medium, and dark roasted beans from C. arabica varieties were carried out. Analysis by HPLC showed higher chlorogenic acid (55 mg/g) and caffeine (1.8 mg/g) contents in the green beans of the Bourbon and Oro Azteca varieties. The caffeine (3.88 mg/g) and melanoidin (97 and 29 mg/g) contents increased according to the level of roasting; a dissimilar effect was found in the chlorogenic acid content (14.5 mg/g). The adequate nutritional content and the sensory evaluation allowed the classification of dark-roasted coffee as premium coffee (84.25 points) and medium-roasted coffee as specialty coffee (86.25 points). The roasted coffees presented antioxidant activity without cytotoxic effects; the presence of CGA and caffeine supports the beneficial effects of drinking coffee. The results obtained will serve as a basis for making decisions on improvements to the coffees analyzed.


Asunto(s)
Cafeína , Coffea , Cafeína/farmacología , Cafeína/análisis , Ácido Clorogénico/farmacología , Ácido Clorogénico/análisis , Coffea/química , Semillas/química , Extractos Vegetales/química
5.
Pharmaceutics ; 15(3)2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36986828

RESUMEN

Neurodegeneration has been associated with chronic inflammation states in the brain. For this reason, attention has been directed to drugs indicated as anti-inflammatory as possible therapies for the treatment of said conditions. Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenyl scopoletin, scoparone, dimethylfraxetin, herniarin, and 7-O-prenylumbelliferone. Therefore, the relationship between the therapeutic effect and the concentration was evaluated through pharmacokinetic and pharmacodynamic studies, including vascular permeability evaluation by blue Evans and pro- and anti-inflammatory cytokines quantification, under a neuroinflammation model induced by lipopolysaccharide by the oral administration of three different doses (5, 10, and 20 mg/kg) of a bioactive fraction of T. lucida. In the present study, it was found that all doses showed a neuroprotective and immunomodulatory effect, although the doses of 10 and 20 mg/kg were able to exert their effect for a longer time and to a greater extent. The protective effects of the fraction may be mainly associated with the DR, HR, and SC coumarins due to their structural profile and plasmatic and brain tissue bioavailability.

6.
Plants (Basel) ; 12(5)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36903951

RESUMEN

The Sphaeralcea angustifolia plant is used as an anti-inflammatory and gastrointestinal protector in Mexican traditional medicine. The immunomodulatory and anti-inflammatory effects have been attributed to scopoletin (1), tomentin (2), and sphaeralcic acid (3) isolated from cells in suspension cultures and identified in the aerial tissues of the wild plant. The hairy roots from S. angustifolia established by infecting internodes with Agrobacterium rhizogenes were explored to produce active compounds based on biosynthetic stability and their capacity to produce new compounds. Chemical analysis was resumed after 3 years in these transformed roots, SaTRN12.2 (line 1) produced scopoletin (0.0022 mg g-1) and sphaeralcic acid (0.22 mg g-1); instead, the SaTRN7.1 (line 2) only produced sphaeralcic acid (3.07 mg g-1). The sphaeralcic acid content was 85-fold higher than that reported for the cells in the suspension cultivated into flakes, and it was similar when the cells in suspension were cultivated in a stirring tank under nitrate restriction. Moreover, both hairy root lines produced stigmasterol (4) and ß-sitosterol (5), as well as two new naphthoic derivates: iso-sphaeralcic acid (6) and 8-methyl-iso-sphaeralcic acid (7), which turned out to be isomers of sphaeralcic acid (3) and have not been reported. The dichloromethane-methanol extract from SaTRN7.1 hairy root line had a gastroprotective effect on an ulcer model in mice induced with ethanol.

7.
Rev. argent. neurocir ; 37(1): 10-20, mar. 2023. ilus
Artículo en Español | LILACS, BINACIS | ID: biblio-1570813

RESUMEN

Objetivos: identificar factores que intervienen en el grado de resección de los meningiomas de base de cráneo y proponer una escala para calcular la probabilidad de resección total. Materiales y métodos: estudio unicéntrico, observacional, retrospectivo, de pacientes operados en el período 06/2018 ­ 06/2022. Se utilizaron como variables: edad, clínica, localización, tamaño, embolización previa, edema perilesional, calcio intratumoral, características en T2 y T1 e invasión ósea. El grado de resección se midió con la clasificación de Simpson tradicional y también se dividió en resección total (Simpson I, II y III) y subtotal (Simpson IV y V). Con los resultados se propuso una escala teniendo en cuenta las variables con significación estadística (p < 0.05). Se realizó una revisión bibliográfica del tema. Resultados: Se operaron un total de 23 pacientes. Fueron estadísticamente significativas asociadas con el grado de Simpson, la localización (p 0,002) y el tamaño (p 0,001). Asociada con resección total y subtotal, la invasión ósea (p 0,013). Para la escala utilizamos: localización (anterior 1 punto, posterior 2 puntos, medial 2 puntos y medial que involucra seno cavernoso 3 puntos), tamaño (<5 cm 1 punto, >5 cm 2 puntos) e invasión ósea (no 1 punto y si 2 puntos). Realizamos un análisis inferencial y se observó asociación entre la escala realizada y el grado de resección (p 0,005). Conclusión: En nuestro estudio se observó una asociación entre el tamaño, la localización y la invasión ósea con el grado de resección conseguido. Propusimos una escala para medir la probabilidad de resección total(AU)


Objectives: identify factors that intervene in the degree of resection of skull base meningiomas and propose a scale to calculate the probability of total resection. Materials and methods: single-center, observational, retrospective study of patients operated in the period 06/2018 - 06/2022. The following variables were used: age, symptoms, location, size, previous embolization, perilesional edema, intratumoral calcium, characteristics in T2 and T1 and bone invasion. The degree of resection was measured using the traditional Simpson scale and was also divided into total (Simpson I, II, and III) and subtotal (Simpson IV and V) resection. With the results, a scale was proposed taking into account the variables with statistical significance (p < 0.05). A bibliographic review of the subject was carried out. Results: A total of 23 patients were operated. They were statistically significant associated with Simpson's grade the location (p 0.002) and size (p 0.001). Associated with total and subtotal resection, the bone invasion (p 0.013). For the scale we use: location (anterior 1 point, posterior 2 points, medial 2 points and medial involving the cavernous sinus 3 points), size (<5 cm 1 point, >5 cm 2 points) and bone invasion (no 1 point and yes 2 points). We performed an inferential analysis and an association was observed between the scale used and the degree of resection (p 0.005). Conclusion: In our study, an association was observed between the size, location and bone invasion with the degree of resection achieved. We proposed a scale to measure the probability of total resection(AU)


Asunto(s)
Meningioma , Cráneo , Seno Cavernoso , Base del Cráneo
8.
Sci Rep ; 13(1): 2066, 2023 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-36739298

RESUMEN

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 µg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.


Asunto(s)
Adenomiosis , Dispareunia , Endometriosis , Humanos , Femenino , Dismenorrea/diagnóstico por imagen , Dismenorrea/tratamiento farmacológico , Endometriosis/diagnóstico por imagen , Endometriosis/tratamiento farmacológico , Adenomiosis/diagnóstico por imagen , Adenomiosis/tratamiento farmacológico , Estudios Prospectivos , Disuria , Estudios de Seguimiento , Dolor Pélvico/diagnóstico por imagen , Dolor Pélvico/tratamiento farmacológico , Anticonceptivos Orales Combinados/uso terapéutico , Anticoncepción , Estreñimiento/tratamiento farmacológico
9.
Neuroscience ; 512: 16-31, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36646411

RESUMEN

No curative or fully effective treatments are currently available for Alzheimer's disease (AD), the most common form of dementia. Electrical stimulation of deep brain areas has been proposed as a novel neuromodulatory therapeutic approach. Previous research from our lab demonstrates that intracranial self-stimulation (ICSS) targeting medial forebrain bundle (MFB) facilitates explicit and implicit learning and memory in rats with age or lesion-related memory impairment. At a molecular level, MFB-ICSS modulates the expression of plasticity and neuroprotection-related genes in memory-related brain areas. On this basis, we suggest that MFB could be a promising stimulation target for AD treatment. In this study, we aimed to assess the effects of MFB-ICSS on both explicit memory as well as the levels of neuropathological markers ptau and drebrin (DBN) in memory-related areas, in an AD rat model obtained by Aß icv-injection. A total of 36 male rats were trained in the Morris water maze on days 26-30 after Aß injection and tested on day 33. Results demonstrate that this Aß model displayed spatial memory impairment in the retention test, accompanied by changes in the levels of DBN and ptau in lateral entorhinal cortex and hippocampus, resembling pathological alterations in early AD. Administration of MFB-ICSS treatment consisting of 5 post-training sessions to AD rats managed to reverse the memory deficits as well as the alteration in ptau and DBN levels. Thus, this paper reports both cognitive and molecular effects of a post-training reinforcing deep brain stimulation procedure in a sporadic AD model for the first time.


Asunto(s)
Enfermedad de Alzheimer , Terapia por Estimulación Eléctrica , Haz Prosencefálico Medial , Trastornos de la Memoria , Animales , Masculino , Ratas , Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides , Modelos Animales de Enfermedad , Haz Prosencefálico Medial/fisiología , Trastornos de la Memoria/terapia , Ratas Wistar , Memoria Espacial/fisiología , Terapia por Estimulación Eléctrica/métodos
10.
Plants (Basel) ; 12(2)2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36679034

RESUMEN

Using herbal medicine is an ancestral cultural practice among Mexicans. A broad sector of society turns to plants to treat priority health problems, a reality that leads scientists to explore the healing value attributed to them. Advances in the experimental research of Sphaeralcea angustifolia confirmed the anti-inflammatory activity of the species; therefore, an analysis of the scope of these studies is now warranted. As such, this paper is a compendium of the advances published in the scientific literature (from 2004 to 2021) on the anti-inflammatory properties of this plant. The promise offered by the species as a potential therapeutic agent is also considered, without dismissing aspects necessary for the preservation of this resource and its cultural and physical environment. The chemical-pharmacological aspects of the wild plant and its in vitro culture are highlighted. The plant's anti-inflammatory properties support its clinical application as an anti-inflammatory phytopharmaceutical to treat arthritic conditions. The sustained therapeutic potential of S. angustifolia is reinforced by the biotechnological processes designed to conserve the resource, thus contributing to the protection of biodiversity and cultural diversity, aspects distinctive of a megadiverse country such as Mexico.

11.
J Comput High Educ ; : 1-18, 2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36714820

RESUMEN

Digital competence is considered to be a crucial learning outcome in education in the 21st century. In this context, research highlights the fact that the perceptions that instructors manifest about different aspects of Information and Communication Technologies (ICTs) condition these professionals' behaviour towards these learning resources. In the same line, this study aims to analyse the effects that exist between a series of dimensions related to the perception of university teaching staff on the capacity of ICTs to respond to different needs of students, on perceived efficacy and attitudes towards these tools and, lastly, on active behaviour towards their use. To do so, 345 university instructors from the Spanish educational system filled in an online questionnaire. The application of a Structural Equation Model underscores the fact that the ability of ICTs to respond to the different needs of students in the university classroom and their perceived efficacy in the teaching-learning process both exert a positive effect on attitudes in favour of their incorporation into the classroom. In turn, these attitudes also have a significant effect on active behaviour with ICT resources. In addition, various mediating effects are seen to influence an active behaviour. All this gives rise to a discussion on the implications of these results to encourage the training of university teaching staff in the knowledge and management of ICTs. Increasing confidence in ICTs as effective tools to respond to different needs could significantly favour positive attitudes and behaviour so that these resources are actively integrated into the classroom.

12.
BMJ Support Palliat Care ; 13(e2): e318-e326, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33707299

RESUMEN

OBJECTIVES: Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. METHODS: This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). RESULTS: A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. CONCLUSION: The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.


Asunto(s)
Neoplasias , Estreñimiento Inducido por Opioides , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Calidad de Vida , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Estudios Prospectivos , Antagonistas de Narcóticos/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico
13.
Plants (Basel) ; 11(21)2022 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-36365258

RESUMEN

Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the chemical compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenylscopoletin (PE), scoparone (SC), dimethylfraxetin (DF), herniarin (HR), and 7-O-prenylumbelliferone (PU), considered potential anti-neuroinflammatory compounds. Therefore, the relationship between the therapeutic effect and the dose can be evaluated through pharmacokinetic-pharmacodynamic (PK-PD) studies under a model of neuroinflammation induced by lipopolysaccharide (LPS). Nonetheless, accomplishing those studies requires an accurate and robust analytical method for the detection of these compounds in different biological matrices of interest. Due to the above, in the present study, a bioanalytical method was established by HPLC-DAD-UV for the simultaneous quantification of the coumarins present in the hexane extract of T. lucida, which was able to determine the temporal concentration profiles of each of the coumarins in the plasma, brain, kidney, and spleen samples of healthy and damaged mice. Coumarins showed an increase in plasma concentrations of up to three times in the neuroinflammation model, compared to healthy mice, so it was possible to quantify the therapeutic agents in the main target organ, the brain. The ability of compounds to cross the blood-brain barrier is an advantage in the treatment of diseases associated with neuroinflammation processes that can be studied in future PK-PD evaluations.

14.
Psicothema ; 34(3): 446-453, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35861007

RESUMEN

BACKGROUND: Intracranial self-stimulation (ICSS) is a technique by which rats press a lever to stimulate their brains through an electrode chronically implanted in brain reward areas. Currently only two laboratories in the world, one in India and one in Spain, are intensively studying the effect of this kind of deep brain stimulation on learning and memory. This paper will present the main findings. METHODS: Different groups of young and old healthy and brain-damaged rats with electrodes implanted in the medial forebrain bundle received a treatment of ICSS after being trained in several paradigms of implicit and explicit learning. Memory was tested over short and long-term periods. Structural and molecular post-mortem analyses of their brains were examined in relation to memory results. RESULTS: ICSS enhances implicit and explicit memory, especially in animals showing poor performance in the learning tasks, such as brain-damaged subjects. At the structural and molecular level, ICSS enhances size and dendritic arborization and promotes neurogenesis in specific hippocampal areas. ICSS also regulates the expression of genes related to learning and memory. CONCLUSIONS: Through activating reward and neural plasticity mechanisms, ICSS in the medial forebrain bundle is a promising technique for memory-enhancing treatments.


Asunto(s)
Haz Prosencefálico Medial , Autoestimulación , Animales , Humanos , Haz Prosencefálico Medial/fisiología , Memoria/fisiología , Ratas , Ratas Wistar , Recompensa , Autoestimulación/fisiología
15.
Plants (Basel) ; 11(2)2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-35050038

RESUMEN

A histological analysis was performed with the aim of elucidating the spontaneous regeneration process of the hairy root lines LRT 2.3 and LRT 6.4, derived from Lopezia racemosa leaf explants and genetically transformed with the Agrobacterium rhizogenes strain ATCC15834/pTDT. The analysis showed both lines regenerate via indirect somatic embryogenesis; LRT 6.4 also regenerated by direct organogenesis. The morphogenic characteristics of the regenerated plantlets from both lines showed the typical characteristics, described previously, including a higher number of axillary shoot formation, short internodes, and plagiotropic roots compared with wild-type seedlings. The regeneration process occurred without the addition of plant growth regulators and was linked to the sucrose concentration in the culture medium. Reducing the sucrose concentration from 3% to 2%, 1%, and 0.5% increased the regeneration rate in LRT 6.4; the effect was less pronounced in LRT 2.3. The cytotoxic activity of different organic extracts obtained from roots and shoots were evaluated in the cancer cell lines HeLa (cervical carcinoma), HCT-15 (colon adenocarcinoma), and OVCAR (ovary carcinoma). The hexane and dichloromethane extracts from roots of both lines showed cytotoxic activity against the HeLa cell line. Only the dichloromethane extract from the roots of PLRT 2.3 showed cytotoxic activity against the OVCAR cell line. None of the methanol extracts showed cytotoxic activity, nor the shoot extracts from any solvent.

16.
Front Behav Neurosci ; 16: 1046259, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36590922

RESUMEN

Intracranial electrical self-stimulation (ICSS) is a useful procedure in animal research. This form of administration ensures that areas of the brain reward system (BRS) are being functionally activated, since the animals must perform an operant response to self-administer an electrical stimulus. Rewarding post-training ICSS of the medial forebrain bundle (MFB), an important system of the BRS, has been shown to consistently improve rats' acquisition and retention in several learning tasks. In the clinical setting, deep brain stimulation (DBS) of different targets is currently being used to palliate the memory impairment that occurs in some neurodegenerative diseases. However, the stimulation of the MFB has only been used to treat emotional alterations, not memory disorders. Since DBS stimulation treatments in humans are exclusively administered by external sources, studies comparing the efficacy of that form of application to a self-administered stimulation are key to the translationality of ICSS. This protocol compares self-administered (ICSS) and experimenter-administered (EAS) stimulation of the MFB on the spatial Morris Water Maze task (MWM). c-Fos immunohistochemistry procedure was carried out to evaluate neural activation after retention. Results show that the stimulation of the MFB improves the MWM task regardless of the form of administration, although some differences in c-Fos expression were found. Present results suggest that MFB-ICSS is a valid animal model to study the effects of MFB electrical stimulation on memory, which could guide clinical applications of DBS. The present protocol is a useful guide for establishing ICSS behavior in rats, which could be used as a learning and memory-modulating treatment.

17.
Psicothema (Oviedo) ; 34(3): 446-453, 2022.
Artículo en Inglés | IBECS | ID: ibc-207340

RESUMEN

Background: Intracranial self-stimulation (ICSS) is a technique by which rats press a lever to stimulate their brains through an electrode chronically implanted in brain reward areas. Currently only two laboratories in the world, one in India and one in Spain, are intensively studying the effect of this kind of deep brain stimulation on learning and memory. This paper will present the main findings. Methods: Different groups of young and old healthy and brain-damaged rats with electrodes implanted in the medial forebrain bundle received a treatment of ICSS after being trained in several paradigms of implicit and explicit learning. Memory was tested over short and long-term periods. Structural and molecular post-mortem analyses of their brains were examined in relation to memory results. Results: ICSS enhances implicit and explicit memory, especially in animals showing poor performance in the learning tasks, such as brain-damaged subjects. At the structural and molecular level, ICSS enhances size and dendritic arborization and promotes neurogenesis in specific hippocampal areas. ICSS also regulates the expression of genes related to learning and memory. Conclusions: Through activating reward and neural plasticity mechanisms, ICSS in the medial forebrain bundle is a promising technique for memory-enhancing treatments.(AU)


Antecedentes: La autoestimulación eléctrica intracraneal (AEIC) es un tipo de estimulación cerebral profunda autoadministrada a través de un electrodo implantado de forma crónica en áreas cerebrales de la recompensa. Actualmente, dos laboratorios en el mundo, uno en India y otro en España, están estudiando intensivamente el efecto de este tipo de estimulación cerebral reforzante sobre el aprendizaje y la memoria. Aquí se presentan los principales hallazgos. Métodos: Diferentes grupos de ratas sanas y con daño cerebral, jóvenes y viejas, con electrodos implantados en el haz prosencefálico medial recibieron un tratamiento de AEIC después de ser entrenados en diferentes paradigmas de aprendizaje. La memoria se evaluó a corto y largo plazo. Resultados: La AEIC mejora la memoria implícita y explícita, especialmente en animales con un bajo rendimiento o con daño cerebral. A nivel estructural y molecular, la AEIC estimula del desarrollo de la arborización dendrítica, promueve la neurogénesis en el hipocampo y regula la expresión de genes relacionados con plasticidad, aprendizaje y memoria. Conclusiones: La AEIC en el haz prosencefálico medial, al activar mecanismos de recompensa y de plasticidad neural, constituye un tratamiento prometedor para la mejora de la memoria.(AU)


Asunto(s)
Animales , Ratones , Autoestimulación , Estimulación Eléctrica , Aprendizaje , Haz Prosencefálico Medial/fisiología , Transmisión Sináptica , Estimulación Encefálica Profunda/psicología , Ratas , Recompensa , Pruebas de Memoria y Aprendizaje , Electrodos , Memoria a Largo Plazo/fisiología , Memoria a Corto Plazo/fisiología , Psicología , Memoria Implícita
18.
Pharmaceuticals (Basel) ; 14(7)2021 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-34202137

RESUMEN

Sphaeralcea angustifolia has been widely used in inflammatory conditions such as blows, bruises, fractures, and wounds. The compounds identified as active in plants and suspension cell culture of S. angustifolia were tomentin, scopoletin, and sphaeralcic acid. To consolidate the integral use of knowledge about the S. angunstifolia and strengthen its pharmacological use in patients with knee osteoarthritis, the pharmacokinetic behavior of the active compounds was characterized. The SaTSS (S. angustifoloia standardized in Tomentin, Scopoletin, and Sphaeralcic acid) anti-ostearthritic fraction was obtained from cell suspension. The analytical method of High-Performance Liquid Chromatography (HPLC) for tomentin, scopoletin, and sphaeralcic acid were validated determining the accuracy, precision linearity, sensibility, specificity, detection limits, and quantification time-range parameters, as well as extraction efficiency and stability of compounds. The pharmacokinetic assay was performed with ICR mice strain, in which the mice were administrated with a single oral or intravenous dose (400 mg/kg with 7.1 mg/kg of scopoletin and tomentin in mixture and 34.6 mg/kg of sphaeralcic acid) of the SaTSS standardized active fraction. The results of the validated analytical methods allowed establishing, in a validated manner, that a coumarin mixture and sphaeralcic acid present in the SaTES fraction were detected in plasma. According to the values of Akaike Information Criteria (AIC), Sum of Squares (SS), Schwarz Criteria (SC), and by the determination coefficient (R2), the compounds follow a two-compartment model.

19.
PLoS One ; 16(6): e0253331, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34161381

RESUMEN

This paper examines the perceptions of firms in April 2020, one month after the Spanish Government declared the state of alarm, about how the COVID-19 pandemic will affect their business activity in the following months, and what employment decisions they expect to make in response. The data for the study was collected by the Government of the region of Aragon (Spain) through a survey of a non-randomly selected sample of firms located in the region. In addition to prospects and intended actions, firms were asked whether or not they had applied for ERTE aid (the Spanish job retention scheme to contain the pandemic crisis). We find that firms participating (voluntarily and anonymously) in the survey anticipated rather well the severity of the effects of the pandemic in the following months. The ERTE aid helped firms to maintain the jobs of their inactive employees, while firms that did not ask for aid responded by laying off employees. Further, the ERTE aid helped to maintain the jobs of furloughed employees, but the firms receiving ERTE aid expected to lay off the same proportion of employees as firms without that aid, controlling for the different anticipated effects of the pandemic in the two groups of firms.


Asunto(s)
COVID-19 , Empleo/economía , Programas de Gobierno , Sector Privado , Desempleo , Gobierno , Humanos , Sector Privado/economía , España , Encuestas y Cuestionarios
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