Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies.

Background/Objectives: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitor-associated intracranial hemorrhage (ICH). Our aim was to describe a compilation of the information available in the literature to date. Methods: PubMed, Embase, Web of Science (Clarivate Analytics) and the Cochrane Central Register of Controlled Trials were searched until December 2023. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review included studies that were retrospective in design and evaluated both drugs to control bleeding and complications (death and thromboembolic events). Two researchers re-examined the studies for relevance, extracted the data and assessed the risk of bias. No meta-analyses were performed for the results. Results: In this limited patient sample, we found no differences between published articles in terms of neuroimaging stability or thrombotic events. However, some studies show significant differences in mortality, suggesting that one of the AAs may be superior to 4F-PCC. Conclusions: Our qualitative analysis shows that AA has a better efficacy profile compared with 4F-PCC. However, further studies monitoring these patients and a multicenter collaborative network dedicated to this topic are needed.

Biochemical Changes in Cardiopulmonary Bypass in Cardiac Surgery: New Insights.

Patients undergoing coronary revascularization with extracorporeal circulation or cardiopulmonary bypass (CPB) may develop several biochemical changes in the microcirculation that lead to a systemic inflammatory response. Surgical incision, post-CPB reperfusion injury and blood contact with non-endothelial membranes can activate inflammatory signaling pathways that lead to the production and activation of inflammatory cells, with cytokine production and oxidative stress. This inflammatory storm can cause damage to vital organs, especially the heart, and thus lead to complications in the postoperative period. In addition to the organic pathophysiology during and after the period of exposure to extracorporeal circulation, this review addresses new perspectives for intraoperative treatment and management that may lead to a reduction in this inflammatory storm and thereby improve the prognosis and possibly reduce the mortality of these patients.

The GPER1 agonist G1 reduces brain injury and improves the qEEG and behavioral outcome of experimental ischemic stroke.

Stroke is one of the principal cerebrovascular diseases in human populations and contributes to a majority of the functional impairments in the elderly. Recent discoveries have led to the inclusion of electroencephalography (EEG) in the complementary prognostic evaluation of patients. The present study describes the EEG, behavioral, and histological changes that occur following cerebral ischemia associated with treatment by G1, a potent and selective G protein-coupled estrogen receptor 1 (GPER1) agonist in a rat model. Treatment with G1 attenuated the neurological deficits induced by ischemic stroke from the second day onward, and reduced areas of infarction. Treatment with G1 also improved the total brainwave power, as well as the theta and alpha wave activity, specifically, and restored the delta band power to levels similar to those observed in the controls. Treatment with G1 also attenuated the peaks of harmful activity observed in the EEG indices. These improvements in brainwave activity indicate that GPER1 plays a fundamental role in the mediation of cerebral injury and in the behavioral outcome of ischemic brain injuries, which points to treatment with G1 as a potential pharmacological strategy for the therapy of stroke.

Oral Treatment with the Extract of Euterpe oleracea Mart. Improves Motor Dysfunction and Reduces Brain Injury in Rats Subjected to Ischemic Stroke.

Ischemic stroke is one of the principal causes of morbidity and mortality around the world. The pathophysiological mechanisms that lead to the formation of the stroke lesions range from the bioenergetic failure of the cells and the intense production of reactive oxygen species to neuroinflammation. The fruit of the açaí palm, Euterpe oleracea Mart. (EO), is consumed by traditional populations in the Brazilian Amazon region, and it is known to have antioxidant and anti-inflammatory properties. We evaluated whether the clarified extract of EO was capable of reducing the area of lesion and promoting neuronal survival following ischemic stroke in rats. Animals submitted to ischemic stroke and treated with EO extract presented a significant improvement in their neurological deficit from the ninth day onward. We also observed a reduction in the extent of the cerebral injury and the preservation of the neurons of the cortical layers. Taken together, our findings indicate that treatment with EO extract in the acute phase following a stroke can trigger signaling pathways that culminate in neuronal survival and promote the partial recovery of neurological scores. However, further detailed studies of the intracellular signaling pathways are needed to better understand the mechanisms involved.

Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats.

Caffeine is a psychoactive substance used worldwide. The present study analyzes the seizure-related behavior and electrocorticographic (ECoG) patterns observed in rats following of a toxic dose of caffeine (150 mg/kg; intraperitoneal). Sixty-three rats were divided into three experiments: 1-Behavior's Description associated with caffeine-induced convulsion; 2- Comparison of the electrocorticographic patterns induced by caffeine and pentylenetetrazole, and 3- Assessment of the electrocorticographic response to antiepileptic drugs (diazepam, phenytoin, and phenobarbital). The behavioral analysis demonstrated tonic-clonic seizures with a loss of postural reflex and a latency of 365.8 s after the caffeine's administration. Caffeine-induced changes in the ECoG were consistent with the development of seizures with rapid evolution and burst potential consistent with the behavioral patterns observed during the caffeine-induced seizure. The ECoG of the brainwaves varied significantly between the seizures caused by caffeine and pentylenetetrazole. The predominant brain forces observed during the seizures were beta-band oscillations. The caffeine-induced seizures were resistant to attempted control with phenytoin and phenobarbital, but responded well to diazepam, which is consistent with a study of Pilocarpine, which showed that diazepam has anticonvulsant effects. These findings are important for the development of effective treatments for caffeine intoxication, in particular for individuals with a low seizure threshold.

A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration.

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa, diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.

100 YEARS OF VITAMIN D: Supraphysiological doses of vitamin D changes brainwave activity patterns in rats.

Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.

Increased Relative Delta Bandpower and Delta Indices Revealed by Continuous qEEG Monitoring in a Rat Model of Ischemia-Reperfusion.

The present study describes the electroencephalographic changes that occur during cerebral ischemia and reperfusion in animals submitted to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 30 min. For this, male Wistar rats were divided into two groups (n = 6 animals/group): (1) sham (control) group, and (2) ischemic/reperfusion group. The quantitative electroencephalography (qEEG) was recorded during the ischemic and immediate reperfusion (acute) phases, and then once a day for 7 days after the MCAO (subacute phase). The acute phase was characterized by a marked increase in the relative delta wave band power (p < 0.001), with a smaller, but significant increase in the relative alpha wave bandpower in the ischemic stroke phase, in comparison with the control group (p = 0.0054). In the immediate reperfusion phase, however, there was an increase in the theta, alpha, and beta waves bandpower (p < 0.001), but no alteration in the delta waves (p = 0.9984), in comparison with the control group. We also observed high values in the delta/theta ratio (DTR), the delta/alpha ratio (DAR), and the (delta+theta)/(alpha+beta) ratio (DTABR) indices during the ischemia (p < 0.05), with a major reduction in the reperfusion phase. In the subacute phase, the activity of all the waves was lower than that of the control group (p < 0.05), although the DTR, DAR, and DTABR indices remained relatively high. In conclusion, early and accurate identification of decreased delta wave bandpower, DTR, DAR, and DTABR indices, and an increase in the activity of other waves in the immediate reperfusion phase may represent an important advance for the recognition of the effectiveness of reperfusion therapy.

Electrocorticographic patterns dominated by low-frequency waves in camphor-induced seizures.

Camphor is an aromatic terpene compound found in the essential oils of many plants, which has been used for centuries as a herbal medicine, especially in children. However, many studies have shown that camphor may have major side effects, including neurological manifestation, such as seizures. In the present study, we investigated the electrocorticographic patterns of seizures induced by camphor in male adult Wistar rats. Each rat received 400 mg/kg (i.p.) of camphor prior to monitoring by electrocorticography. The application of camphor resulted a rapid evolution to seizure and marked changes in the electrocorticographic readings, which presented characteristics of epileptiform activity, with an increase in the total power wave. The decomposition of the cerebral waves revealed an increase in the delta and theta waves. The analysis of the camphor traces revealed severe ictal activity marked by an increase in the polyspike wave. Our data thus indicate that camphor may cause seizures, leading to tonic-clonic seizures. Clearly, further studies are necessary to better elucidate the mechanisms through which camphor acts on the brain, and to propose potential treatments with anticonvulsant drugs that are effective for the control of the seizures.

Alteration of Testosterone Levels Changes Brain Wave Activity Patterns and Induces Aggressive Behavior in Rats.

Testosterone is responsible for several changes in the brain, including behavioral and emotional responses, memory, and cognition. Given this, we investigated changes in the brain wave profile caused by supplementation with exogenous testosterone in both castrated and non-castrated rats. We also investigated the serum testosterone levels, renal and hepatic function, and the lipid and behavioral profiles. We found changes in the spectral wave power in both groups (castrated and non-castrated animals) supplemented with exogenous testosterone, consistent with an aggressive/hostile profile. These changes were observed in the electrocorticographic evaluation associated with increased power in low-frequency (delta and theta) and high-frequency (beta and gamma) activity in the supplemented animals. The castrated animals presented a significant decrease of wave power in the alpha frequency. This correlated with a decrease of the performance of the animals in the elevated plus-maze evaluation, given that the alpha wave is linked to the execution and visualization of motor processes. In the behavioral evaluation, the castrated animals presented a reduced permanence time in the elevated-plus maze, although this was prevented by the supplementation of testosterone. Testosterone supplementation induced aggressive behavior in non-castrated animals, but not in castrated ones. Supplemented animals had significantly elevated serum testosterone levels, while their urea levels were significantly lower, but without clinical significance. Our data indicate that testosterone supplementation in non-castrated rats, but not in castrated ones, causes electrocorticographic changes that could be associated with more aggressive and hostile behavior, in addition to indicating a potential for personality disorder. However, further studies are required to elucidate the cellular and molecular changes caused by acute testosterone supplementation.

APC gene is modulated by hsa-miR-135b-5p in both diffuse and intestinal gastric cancer subtypes.

BACKGROUND: Several genetic and epigenetic alterations are related to the development and progression of Gastric Cancer (GC), one of those being the deregulated microRNA (miRNA) expression profile. miRNAs are small noncoding RNAs that negatively regulate the expression of thousands of genes, including oncogenes and tumor suppressor genes. Our group identified, in previous studies, some miRNAs that are differentially expressed in GC when compared to the gastric mucosa without cancer, including hsa-miR-29c and hsa-miR-135b. The aim of the study was to modulate the expression of the miRNAs hsa-miR-29c-5p and hsa-miR-135b-5p and evaluate the expression of their target genes in 2D and 3D cell cultures. METHODS: hsa-miR-29c-5p and hsa-miR-135b-5p expression profiles were modulated by transfecting mimics and antimiRs, respectively, in 2D and 3D cell cultures. The expression of the proteins coded by the genes CDC42, DNMT3A (target genes of hsa-miR-29c-5p) and APC (target gene of hsa-miR-135b-5p) were measured by Western Blot. RESULTS: Results showed that mimics and antimiRs transfection significantly altered the expression of both miRNAs, increasing the expression of hsa-miR-29c-5p and reducing the expression of hsa-miR-135b-5p, especially in the 3D culture of the cell lines. When analyzing the proteins expression, we observed that AGP01 and AGP03 cell lines transfected with mimics had a reduction in the levels of CDC42 and DNMT3A and all three cell lines transfected with antimiRs had an increase in the expression of the protein APC. CONCLUSION: We concluded that three-dimensional culture can be a more representative in vitro model that resembles better the in vivo reality. Our results also showed that hsa-miR-29c-5p is an important regulator of CDC42 and DNMT3A genes in the intestinal subtype gastric cancer and hsa-miR-135b-5p regulates the APC gene in both intestinal and diffuse subtypes of GC. Dysregulation in their expression, and consequently in their respectively signaling pathways, shows how these miRNAs can influence the carcinogenesis of different histological subtypes of gastric cancer.

Perfil leucocitário de pacientes atendidos em um laboratório da rede pública de saúde / Leukocyte profile of patients taken care of a laboratory health public system

caracterizar o perfil leucocitário de uma população socialmente carente, de acordo com as alterações mais comumente observadas. Método: analisados os dados quantitativos de 1.141 leucogramas de pacientes do Laboratório de Análises Clínicas do Instituto de Ciências Biológicas da Universidade Federal do Pará, realizados no ano de 2006. Estes foram categorizados em quatro grupos: crianças, mulheres, homens e idosos. Notou-se que as alterações nos valores absolutos em cada tipo leucocitário dificilmente estavam associadas à leucocitose ou à leucopenia, ou com alterações nos valores percentuais de um mesmo grupo leucocitário. Foi possível observar maior prevalência de leucocitoses em mulheres e em idosas, e de leucopenias em crianças e em homens. Apreciadas no total de pacientes, as alterações de maior prevalência foram a eosinofilia e a linfopenia, com maior destaque em mulheres e em crianças do sexo feminino. A linfopenia é observada principalmente no diagnóstico de deficiências nutricionais. O aumento de eosinófilos é relacionado a alergias ou a parasitoses provocadas por helmintos, o que pode resultar em outras patologias como a anemia. Foram observados 44% de casos isolados de anemia, principalmente em mulheres, e a associação mais comum da anemia foi com eosinofilia (19,1%). Conclusões: tais resultados mostram que existe uma importante relação entre carência de saúde e baixas condições sócio-econômicas

The aim is to characterize of leukocyte profile of a socially devoid population, in according with the alterations observed usually, we evaluated quantitative data of 1,141 leucograms of patients of Laboratory of Clinics Analyses of The Biological Sciences Institute in Federal University of Para, collected in 2006. These had been categorized in four groups: children, women, men, and aged. We noted that alterations in absolutes values in each type of leukocyte hardly were associates to leukocytosis or leukopenia, or with alterations in percent values in the same leukocytes group. It was possible observe the most prevalence of leukocytosis in women and aged female, and leukopenia in children and men. Appreciated in the total patients, the alterations of most prevalence were eosinophilia and lymphopenia, with evidence in women and children female. The lymphopenia is rather than noted in diagnosis of nutritious deficiencies. Eosinophils increased are related to allergies or parasitism evoked to helminthes, which can result in others pathologies like anemia. We also observed 44% of isolated cases of anemia, mainly in women, and the association most common with anemia was eosinophilia (19.1%). Such findings allow concluding that there is an important relationship between lack of health and poor social-economic conditions.