Anatomical study of serotonergic innervation and 5-HT1A receptor in the human spinal cord

Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. Translation to either pharmacological and/or cellular therapies in humans requires the mapping of the spinal cord 5-HT innervation and its receptors to determine their involvement in specific functions. Here, we have performed a preliminary mapping of serotonergic processes and serotonin-lA (5-HT1A) receptors in thoracic and lumbar segments of the human spinal cord. As in rodents and non-human primates, 5-HT profiles in human spinal cord are present in the ventral horn, surrounding motoneurons, and also contact their presumptive dendrites at lumbar level. 5-HT1A receptors are present in the same area, but are more densely expressed at lumbar level. 5-HT profiles are also present in the intermediolateral region, where 5-HT1A receptors are absent. Finally, we observed numerous serotonergic profiles in the superficial part (equivalent of Rexed lamina II) of the dorsal horn, which also displayed high levels of 5-HT1A receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers

SEMI-COVID-19 Network.[Background] The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined.[Objective] We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. .[Design] A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and d-dimer values.[Patients] A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ).[Main Measures] The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission.[Key Results] A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high–risk category (31.9% vs. 23.9%, p=0.049).[Conclusions] The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.Peer reviewe

ICO-ICS Praxis para el tratamiento médico y con irradiación del linfoma B difuso de célula grande

Tractament mèdic; Tractament amb irradiació; Limfoma B difús de cèl·lula granMedical treatment; Irradiation treatment; Diffuse large cell B lymphomaTratamiento médico; Tratamiento con irradiación; Linfoma B difuso de célula grandeEls limfomes no hodgkinians (LNH) són neoplàsies originades en cèl·lules limfoides en diferents estats maduratius, la qual cosa explica la gran heterogeneïtat biològica i clínica d’aquests tumors. Hi ha diversos sistemes de classificació, però el més utilitzat és la Classificació euroamericana revisada de limfomes de l'Organització Mundial de la Salut. El limfoma B difús de cèl·lula gran suposa aproximadament entre el 30-40% dels limfomes dels adults. Habitualment afecta adults amb una edat mitjana superior a 60 anys i el 60% dels pacients presenten els anomenats símptomes B (febre de 38 ºC o més, pèrdua de pes de més del 10% i/o sudoració nocturna. La majoria de casos són formes de novo però també poden ser deguts a la progressió o transformació d’una malaltia limfoproliferativa prèvia. Els objectius d'aquest document són: Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi del limfoma B difús de cèl·lula gran. - Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. - Implementar els resultats de la terapèutica en els pacients amb limfoma B difús de cèl·lula gran tractats d’acord amb les recomanacions d’aquesta guia

Journal of Endocrinology and Diabetes Mellitus, 2013, 1, 37-48 37 Dietary Patterns, Anthropometry and Metabolic Cardiovascular

Abstract: Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Early detection of high-risk individuals is essential in order to adopt more effective preventive and therapeutic measures. One of the most controversial issues today is how to manage eating habits in order to establish the best diet: current data suggest that promotion of healthy eating habits—consumption of fruit and vegetables, limitation of fat intake to unsaturated fats— could help to significantly reduce the number of cardiovascular risk factors and the risk of suffering from metabolic syndrome, and that maintaining these measures over time could help maintain, and even reduce, body weight. Some recent studies, likes DORICA study analyzes the association between the predominant dietary patterns and the presence of cardiovascular risk factors. The hypothesis is that the most traditional consumption patterns (for example the Mediterranean diet) are associated with a healthier cardiovascular profile in the Spanish adult population. The results of DORICA revealed that energy intake was 2560 (797) kcal in men and 2230 (665) kcal in women, and that fats accounted for 39.3 % of energy intake in women and 37 % in men. In other words, 47 % of men and 64 % of women have fat intakes that are above the recommended levels. In addition, 87 % have cholesterol levels above 100 mg/1000 kcal, especially men younger than 45 years (89%). This study analyze 3 types of dietary patterns: I) high-protein pattern, with a high consumption of meat, cereals, potatoes, and alcoholic drinks; II) unbalanced pattern, with a high consumption of milk and its derivatives, and a lo

Analysis of the Impact of African Dust Storms on the Presence of Enteric Viruses in the Atmosphere in Tenerife, Spain

Airborne viruses and their relation to dust storms, as a possible route for dispersion, have not been widely investigated. There are, however, studies that have described the airborne dispersal of pathogenic viruses and their potential impact on public and agronomical health. Atmospheric samples were collected in an urban area of Tenerife during 2009, 2010, 2012 and 2013 and screened for the presence of enteric viruses using PCR and sequencing. The potential relationship of viral data with African dust storms and other climatic variables (viz., the seasonality, origin of the air mass and PM levels) was analyzed. Enteroviruses and Rotaviruses were detected in 15.4% (20/130) and 36.9% (48/130) of the samples, respectively. No significant statistical relationships were observed with African dust storms or the origin of the air masses, although higher percentages of positives were obtained for dust storm days. Enterovirus detection was significantly linked to warmer seasons, and PM2.5 levels showed an inverse correlation with a rotaviral presence. This is the first multi-year report to describe the presence of Enterovirus and Rotavirus genetic sequences in air samples collected in an outdoor urban environment. The data illustrates the need for source region sampling to determine links and the influence of the weather and climatic and regional wind patterns on long-range atmospheric dispersion of viruses in future research efforts

Development of NMDAR antagonists with reduced neurotoxic side effects: a study on GK11

The NMDAR glutamate receptor subtype mediates various vital physiological neuronal functions. However, its excessive activation contributes to neuronal damage in a large variety of acute and chronic neurological disorders. NMDAR antagonists thus represent promising therapeutic tools that can counteract NMDARs’ overactivation. Channel blockers are of special interest since they are use-dependent, thus being more potent at continuously activated NMDARs, as may be the case in pathological conditions. Nevertheless, it has been established that NMDAR antagonists, such as MK801, also have unacceptable neurotoxic effects. Presently only Memantine is considered a safe NMDAR antagonist and is used clinically. It has recently been speculated that antagonists that preferentially target extrasynaptic NMDARs would be less toxic. We previously demonstrated that the phencyclidine derivative GK11 preferentially inhibits extrasynaptic NMDARs. We thus anticipated that this compound would be safer than other known NMDAR antagonists. In this study we used whole-genome profiling of the rat cingulate cortex, a brain area that is particularly sensitive to NMDAR antagonists, to compare the potential adverse effects of GK11 and MK801. Our results showed that in contrast to GK11, the transcriptional profile of MK801 is characterized by a significant upregulation of inflammatory and stress-response genes, consistent with its high neurotoxicity. In addition, behavioural and immunohistochemical analyses confirmed marked inflammatory reactions (including astrogliosis and microglial activation) in MK801-treated, but not GK11-treated rats. Interestingly, we also showed that GK11 elicited less inflammation and neuronal damage, even when compared to Memantine, which like GK11, preferentially inhibits extrasynaptic NMDAR. As a whole, our study suggests that GK11 may be a more attractive therapeutic alternative in the treatment of CNS disorders characterized by the overactivation of glutamate receptors