Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats.

Impaired gas exchange close to labor causes perinatal asphyxia (PA), a neurodevelopmental impairment factor. Palmitoylethanolamide (PEA) proved neuroprotective in experimental brain injury and neurodegeneration models. This study aimed to evaluate PEA effects on the immature-brain, i.e., early neuroprotection by PEA in an experimental PA paradigm. Newborn rats were placed in a 37°C water bath for 19 min to induce PA. PEA 10 mg/kg, s.c., was administered within the first hour of life. Neurobehavioral responses were assessed from postnatal day 1 (P1) to postnatal day 21 (P21), recording the day of appearance of several reflexes and neurological signs. Hippocampal CA1 area ultrastructure was examined using electron microscopy. Microtubule-associated protein 2 (MAP-2), phosphorylated high and medium molecular weight neurofilaments (pNF H/M), and glial fibrillary acidic protein (GFAP) were assessed using immunohistochemistry and Western blot at P21. Over the first 3 weeks of life, PA rats showed late gait, negative geotaxis and eye-opening onset, and delayed appearance of air-righting, auditory startle, sensory eyelid, forelimb placing, and grasp reflexes. On P21, the hippocampal CA1 area showed signs of neuronal degeneration and MAP-2 deficit. PEA treatment reduced PA-induced hippocampal damage and normalized the time of appearance of gait, air-righting, placing, and grasp reflexes. The outcome of this study might prove useful in designing intervention strategies to reduce early neurodevelopmental delay following PA.

Multidimensional overview of neurofilament light chain contribution to comprehensively understanding multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by demyelination, progressive axonal loss, and varying clinical presentations. Axonal damage associated with the inflammatory process causes neurofilaments, the major neuron structural proteins, to be released into the extracellular space, reaching the cerebrospinal fluid (CSF) and the peripheral blood. Methodological advances in neurofilaments' serological detection and imaging technology, along with many clinical and therapeutic studies in the last years, have deepened our understanding of MS immunopathogenesis. This review examines the use of light chain neurofilaments (NFLs) as peripheral MS biomarkers in light of the current clinical and therapeutic evidence, MS immunopathology, and technological advances in diagnostic tools. It aims to highlight NFL multidimensional value as a reliable MS biomarker with a diagnostic-prognostic profile while improving our comprehension of inflammatory neurodegenerative processes, mainly RRMS, the most frequent clinical presentation of MS.

Corrigendum: Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats.

[This corrects the article DOI: 10.3389/fnbeh.2022.953157.].

Adipokines, Cardiovascular Risk, and Therapeutic Management in Obesity and Psoriatic Arthritis.

Psoriatic arthritis is a chronic inflammatory disease with skin and joint pathology as the dominant characteristics. Scientific evidence supports its systemic nature and relevant relationship with obesity, metabolic syndrome, and associated conditions. Metabolic syndrome and obesity share common signaling pathways with joint inflammation, reinforcing the idea that adipose tissue is a major contributor to disease development and severity. The adipose tissue is not a mere energy store but also an endocrine organ participating in the immune response. In the search for the best therapeutic strategy for a patient, we should appraise the adipose tissue as an endocrine and immune organ responsible for mild chronic inflammation. Today, our challenge is not only to achieve disease remission but to control the associated comorbidities as well. In light of the high prevalence of obesity in psoriatic arthritis patients and the importance of the adipose tissue in the development of chronic inflammation, we aimed to identify the most relevant articles in this regard published in English until June 2020 using the PubMed database. Search terms included psoriatic arthritis, in combination with metabolic syndrome, obesity, adipokines, cardiovascular disease, and treatment. This review summarizes the current evidence regarding the role of adipose tissue as an adipokine-secreting endocrine organ, discussing its influence on disease development and severity, and ultimately in meeting successful disease management.

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia.

Perinatal asphyxia (PA) is a clinical condition brought by a birth temporary oxygen deprivation associated with long-term damage in the corpus striatum, one of the most compromised brain areas. Palmitoylethanolamide (PEA) is a neuromodulator well known for its protective effects in brain injury models, including PA, albeit not deeply studied regarding its particular effects in the corpus striatum following PA. Using Bjelke et al. (1991) PA model, full-term pregnant rats were decapitated, and uterus horns were placed in a water bath at 37°C for 19 min. One hour later, the pups were injected with PEA 10 mg/kg s.c., and placed with surrogate mothers. After 30 days, the animals were perfused, and coronal striatal sections were collected to analyze protein-level expression by Western blot and the reactive area by immunohistochemistry for neuron markers: phosphorylated neurofilament-heavy/medium-chain (pNF-H/M) and microtubule-associated protein-2 (MAP-2), and the astrocyte marker, glial fibrillary acidic protein (GFAP). Results indicated that PA produced neuronal damage and morphological changes. Asphyctic rats showed a decrease in pNF-H/M and MAP-2 reactive areas, GFAP+ cells number, and MAP-2 as well as pNF-H/M protein expression in the striatum. Treatment with PEA largely restored the number of GFAP+ cells. Most important, it ameliorated the decrease in pNF-H/M and MAP-2 reactive areas in asphyctic rats. Noticeably, PEA treatment reversed the decrease in MAP-2 protein expression and largely prevented PA-induced decrease in pNF-H/M protein expression. PA did not affect the GFAP protein level. Treatment with PEA attenuated striatal damage induced by PA, suggesting its therapeutic potential for the prevention of neurodevelopmental disorders.

Immune-Mediated Inflammation Promotes Subclinical Atherosclerosis in Recent-Onset Psoriatic Arthritis Patients without Conventional Cardiovascular Risk Factors.

Studies on the inflammatory burden in recent-onset psoriatic arthritis (PsA) patients without conventional cardiovascular risk factors (CVRFs) are not available. This preliminary study focuses on cardiovascular risk in cutaneous psoriasis (CPs) and recent-onset PsA patients. Blood biochemistry (glucose, cholesterol, uric acid, lipid profile and apolipoprotein B) was analyzed using standard kits. Proatherogenic inflammation markers, C-reactive protein (CRP) and interleukin-6 (IL-6), and endothelial activators monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 (sICAM-1), were determined by enzyme-linked immunosorbent assay. Ultrasound images allowed measuring carotid intima-media thickness (cIMT). Our study first shows an increase in cIMT, and in serum levels of sICAM-1 and CRP in recent-onset PsA patients not presenting conventional CVRFs over the non-medicated time-period, from disease diagnosis to the beginning of pharmacological treatment, compared with healthy subjects. The outcome highlights the importance of monitoring serum level of sICAM1, CRP, and cIMT, and the value of primary prevention in psoriatic patients even with no history of cardiovascular events.

Chagas disease prevalence in pregnant women: migration and risk of congenital transmission.

INTRODUCTION: Argentina has been a preferential target for Bolivian immigrants for decades. The relatively recent migratory flux includes Germany, France, the United States, Australia, Japan, and some Latin American countries. The aim of this cross-sectional study was to describe the prevalence of Chagas disease in pregnant women, analyzing the Bolivian-specific Chagas prevalence as the main contributor of migratory populations from Chagas disease-endemic areas to Buenos Aires city, Argentina, and to evaluate the impact of these migrant influxes on the process of the "urbanization" of the disease in reference hospital José Maria Ramos Mejia (JMRM). METHODOLOGY: Overall, 21,332 pregnant women (100%) between 15 and 49 years of age derived from the public maternity service of JMRMH were studied. Serology data was obtained from registered serological diagnosis data, consisting of three different serological tests performed at the Public Parasitology Unit. RESULTS: Although general prevalence decreased during the analyzed period, the specific prevalence of pregnant women from Bolivian origin showed a sustained growth during 1983-2013. Solely 5% of the total pregnant women population from Bolivia contributed to one third of the total Chagas prevalence. CONCLUSIONS: This study showed that a cohort of pregnant women from Bolivia who attended JMRMH during the period 1983-2007 constituted a population at risk for congenital transmission. Increased migration from endemic areas of Bolivia might potentially increase the prevalence of Chagas disease among pregnant women. In addition, this study highlights the importance to analyze specific prevalence according to endemic areas to determine the profiles of potential hidden prevalence.

Antiproliferative effect of sera from chagasic patients on Trypanosoma cruzi epimastigotes. Involvement of xanthine oxidase.

Serum from asymptomatic or symptomatic (with cardiovascular manifestations) chagasic patients depleted of the complement system displayed an antiproliferative effect on Trypanosoma cruzi epimastigotes, RA strain, when added to the growth medium. This effect was also observed when patient's serum was depleted of specific antibodies. The antiproliferative effect was both time and concentration dependent. It was confined to the non-dialyzable, high molecular weight, fraction of the serum. This effect was abrogated by allopurinol and catalase, and enhanced by N-ethylmaleimide. Xanthine oxidoreductase and xanthine oxidase activities were increased in the chagasic sera, while catalase activity remained unchanged. Parasites exposed to chagasic sera showed a decrease in Fe/superoxide dismutase activity as well as an increase in membrane lipoperoxidation. Our data provides evidence to support the idea that the antiproliferative activity observed in sera from chagasic patients may be due, at least partially, to a direct effect of hydrogen peroxide on the epimastigotes of T. cruzi. The increase of hydrogen peroxide to antiproliferative levels might result from an increase in xanthine oxidase activity in the serum of patients infected with the parasite.

Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver.

In the present study, the effects of hexachlorobenzene (HCB) on epidermal growth factor receptor (EGFR) content of liver microsomes and plasma membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were investigated. In addition, we studied the parameters of the tyrosine kinase signalling pathway such as protein tyrosine kinase (PTK) activity and phosphotyrosine content in microsomal and cytosolic protein. To determine whether the observed alterations were correlated with a manifestation of overt toxicity, a single very low dose of HCB (1mg/kg body wt) and two much higher doses (100 and 1000 mg/kg body wt), the highest being toxicologically significant in that it reduced serum thyroxine (T(4)) and inhibited uroporphyrinogen decarboxylase (URO-D) (EC 4.1.1.37) activity, were tested. Our results demonstrated that liver microsomes of rats treated with HCB had higher levels of EGFR than untreated rats; treated rats also had less EGFR present in hepatocyte plasma membrane fractions than did untreated rats. HCB altered the phosphotyrosine content and protein phosphorylation of some microsomal and cytosolic proteins in a biphasic dose-response relationship. At the low dose, phosphorylation and phosphotyrosine content of several microsomal proteins were increased; however, these effects were diminished or reversed at the higher doses. Our results suggest that chronic HCB treatment produces a down-regulation of the EGFR and a dose-dependent increase in EGFR-tyrosine kinase activity in the microsomal fraction. This effect may contribute to the alteration of membrane and cytosolic protein tyrosine phosphorylation. The level of sensitivity encountered in our studies is extraordinary, occurring at 1/10 to 1/1000 the doses of HCB known to cause other toxicological lesions.

Variations of the cAMP levels in fish ovaries: effect of human chorionic gonadotropin in vitro and of haloperidol in vivo

Se ha desarrollado un ensayo para la determinación de la actividad gonodotrópica en peces hembra, basado en la medición de las variaciones de AMPc en ovario, por medio de un método de radiocompetición proteica. Con ovarios de Cichlasoma facetum, se establecieron las condiciones para la inducción in vitro con gonadotrofina coriónica humana (hCG): 1) preincubación en 1 ml de medio a 30MC durante 60 m; 2) incubación en 1 ml de medio con HCG a 30§C durante 60 m. Este esuqema fue usado en ovarios de Betta splendens de 3-4 meses de edad sexualmente maduras. En una serie de experimentos, se determinó que 50 UI o más de hCG por tubo de incubación, producen un aumento significativo de AMPc con respecto a los controles y que la respuesta es dosis dependiente. El efecto de una inyección intraperitoneal de haloperidol, un antagonista de la dopamina, se estudió en hembras Betta splendens de 3-4 meses de edad sexualmente maduras. Con bajas dosis se observó una tendencia al aumento de AMPc (1 microng/gm de peso corporal) y con mayores dosis (10 microng/gm de peso corporal) hubo un aumento significativo luego de 6 h de la administración. No se observó respuesta a las 24 h. Este trabajo muestra que, como en otros teleósteos, la dopamina actúa como un factor inhibidor de la liberación de gonadotrofina hipofisaria (GRIF) en B. splendens, dado que la admistración de haloperidos induce un aumento de la actividad gonadotrópica