E3 Ubiquitin Ligase Smurf1 Regulates the Inflammatory Response in Macrophages and Attenuates Hepatic Damage during Betacoronavirus Infection.

The E3 ubiquitin ligase Smurf1 catalyzes the ubiquitination and proteasomal degradation of several protein substrates related to inflammatory responses and antiviral signaling. This study investigated the role of Smurf1 in modulating inflammation induced by Betacoronavirus infection. Bone marrow-derived macrophages (BMDMs) from C57BL/6 (wild-type) or Smurf1-deficient (Smurf1-/-) mice were infected with MHV-A59 to evaluate the inflammatory response in vitro. Smurf1 was found to be required to downregulate the macrophage production of pro-inflammatory mediators, including TNF, and CXCL1; to control viral release from infected cells; and to increase cell viability. To assess the impact of Smurf 1 in vivo, we evaluated the infection of mice with MHV-A59 through the intranasal route. Smurf1-/- mice infected with a lethal inoculum of MHV-A59 succumbed earlier to infection. Intranasal inoculation with a 10-fold lower dose of MHV-A59 resulted in hematological parameter alterations in Smurf1-/- mice suggestive of exacerbated systemic inflammation. In the lung parenchyma, Smurf1 expression was essential to promote viral clearance, downregulating IFN-ß mRNA and controlling the inflammatory profile of macrophages and neutrophils. Conversely, Smurf1 did not affect IFN-ß mRNA regulation in the liver, but it was required to increase TNF and iNOS expression in neutrophils and decrease TNF expression in macrophages. In addition, Smurf1-/- mice exhibited augmented liver injuries, accompanied by high serum levels of alanine aminotransferase (ALT). These findings suggest that Smurf1 plays a critical role in regulating the inflammatory response in macrophages and attenuating systemic inflammation during Betacoronavirus infection.

Protection of stromal cell-derived factor-1 SDF-1/CXCL12 against proteases yields improved skin wound healing.

SDF-1/CXCL12 is a unique chemotactic factor with multiple functions on various types of precursor cells, all carrying the cognate receptor CXCR4. Whereas individual biological functions of SDF-1/CXCL12 have been well documented, practical applications in medicine are insufficiently studied. This is explained by the complex multifunctional biology of SDF-1 with systemic and local effects, critical dependence of SDF-1 activity on aminoterminal proteolytic processing and limited knowledge of applicable modulators of its activity. We here present new insights into modulation of SDF-1 activity in vitro and in vivo by a macromolecular compound, chlorite-oxidized oxyamylose (COAM). COAM prevented the proteolytic inactivation of SDF-1 by two inflammation-associated proteases: matrix metalloproteinase-9/MMP-9 and dipeptidylpeptidase IV/DPPIV/CD26. The inhibition of proteolytic inactivation was functionally measured by receptor-mediated effects, including intracellular calcium mobilization, ERK1/2 phosphorylation, receptor internalization and chemotaxis of CXCR4-positive cells. Protection of SDF-1/CXCL12 against proteolysis was dependent on electrostatic COAM-SDF-1 interactions. By in vivo experiments in mice, we showed that the combination of COAM with SDF-1 delivered through physiological fibrin hydrogel had beneficial effect for the healing of skin wounds. Collectively, we show that COAM protects SDF-1 from proteolytic inactivation, maintaining SDF-1 biological activities. Thus, protection from proteolysis by COAM represents a therapeutic strategy to prolong SDF-1 bioavailability for wound healing applications.

Determinants of anuran assemblages in Amazonian White-sand Ecosystems.

Amazonian white-sand ecosystems have predominantly sandy soils and a high amount of endemism, and several species found within them are adapted to long periods of drought. However, little is known about the variation in the structure of anuran assemblages in these ecosystems. Considering that most species are not uniformly distributed in heterogeneous landscapes, we tested the hypothesis that anuran assemblage variation in white-sand ecosystems is related to changes in vegetation structure. Specifically, we focused on a heterogeneous patch of white-sand ecosystems of the central Amazon and evaluated whether vegetation structure and soil characteristics, including root depth, influence the richness, abundance, and composition of anuran assemblages. Our results showed that low amounts of clay in the soil play an important role in structuring vegetation in these ecosystems, and these are the main factors that organize anuran assemblages. The Campinaranas close to the water bodies have a high species richness, while Campina landscapes limit the occupation of most of species. Our findings indicate that anurans undergo environmental filtering in white-sand ecosystems and are organized into hierarchical subgroups, in which only species with specialized reproduction can successfully occupy the most water-restricted environments.

Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.

Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inhibitory efficacy towards a panel of proteases including trypsin, chymotrypsin, ACE2, elastase, and cathepsins B and L. The fractions did not interfere with SARS-CoV-2 infection of Vero E6 cells in vitro. Importantly, two of the fractions fully inhibited elastin-degrading activity of complete primary human neutrophil degranulate. These data warrant further development of potato PI fractions for biomedical purposes, including tissue damage crucial to SARS-CoV-2 pathogenesis. KEY MESSAGES: Protease inhibitor fractions from potato differentially inhibit a series of human proteases involved in viral replication and in tissue damage by overshoot inflammation. Protease inhibition of cell surface receptors such as ACE2 does not prevent virus infection of Vero cells in vitro. Protease inhibitors derived from potato can fully inhibit elastin-degrading primary human neutrophil proteases. Protease inhibitor fractions can be produced at high scale (hundreds of thousands of kilograms, i.e., tons) allowing economically feasible application in lower and higher income countries.

Aplicação de farinhas de coprodutos de frutas em bolos sem glúten / Application of fruit co-product flours in gluten-free cakes

O presente estudo teve como objetivo empregar farinhas de coprodutos de frutas em bolos sem glúten e analisar a qualidade sensorial e tecnológica das receitas. Foi desenvolvido um bolo padrão e seis com adição de 14% de cada farinha de coproduto. Foi realizada avaliação de volume, dureza instrumental e análise sensorial de aceitação. O bolo com farinha da casca de banana apresentou os melhores resultados de volume e dureza, enquanto o bolo com farinha da casca de abacaxi os piores resultados, menor volume e maior dureza. As diferenças de cor dos bolos foram refletidas pela característica de cada farinha adicionada. Todos os bolos atingiram mais de 70% de aceitabilidade sensorial, demonstrando a viabilidade das aplicações. Conclui-se que a utilização de farinhas produzidas com coprodutos de frutas em bolos é uma opção para uma alimentação saudável e sustentável, em especial, para indivíduos celíacos. (AU)

The present study aimed to use fruit co-product flours in gluten-free cakes and analyze the sensorial and technological quality of the recipes. One standard and six cakes were developed by the addition of 14% of each co-product flour. Volume, instrumental hardness and sensory acceptance analysis were performed. The cake with banana peel flour showed the best results for volume and hardness, while the cake with pineapple peel flour had the worst results, lower volume and higher hardness. The differences in cake colors were reflected by the characteristics of each flour added. All cakes reached more than 70% of sensorial acceptability, demonstrating the viability of the applications. The use of flours produced with fruit co-products in cakes is therefore an option for a healthy and sustainable diet, especially for individuals with celiac disease. (AU)

A 5-Lipoxygenase Inhibitor, Zileuton, Modulates Host Immune Responses and Improves Lung Function in a Model of Severe Acute Respiratory Syndrome (SARS) Induced by Betacoronavirus.

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs three days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV-2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host's capacity to deal with infection.

Physiological fibrin hydrogel modulates immune cells and molecules and accelerates mouse skin wound healing.

Introduction: Wound healing is a complex process to restore homeostasis after injury and insufficient skin wound healing is a considerable problem in medicine. Whereas many attempts of regenerative medicine have been made for wound healing with growth factors and cell therapies, simple pharmacological and immunological studies are lagging behind. We investigated how fibrin hydrogels modulate immune cells and molecules in skin wound healing in mice. Methods: Physiological fibrin hydrogels (3.5 mg/mL fibrinogen) were generated, biophysically analyzed for stiffness and protein contents and were structurally studied by scanning electron microscopy. Physiological fibrin hydrogels were applied to full thickness skin wounds and, after 3 days, cells and molecules in wound tissues were analyzed. Leukocytes, endothelial cells, fibroblasts and keratinocytes were explored with the use of Flow Cytometry, whereas cytokines and matrix metalloproteinases were analyzed with the use of qPCR, ELISAs and zymography. Skin wound healing was analyzed microscopically at day 3, macroscopically followed daily during repair in mice and compared with commercially available fibrin sealant Tisseel. Results: Exogenous fibrin at physiological concentrations decreased neutrophil and increased non-classical Ly6Clow monocyte and resolutive macrophage (CD206+ and CX3CR1+) populations, at day 3 after injury. Fibrin hydrogel reduced the expression of pro-inflammatory cytokines and increased IL-10 levels. In line with these findings, gelatinase B/MMP-9 was decreased, whereas gelatinase A/MMP-2 levels remained unaltered. Frequencies of dermal endothelial cells, fibroblasts and keratinocytes were increased and keratinocyte migration was enhanced by fibrin hydrogel. Importantly, physiological fibrin accelerated the healing of skin wounds in contrast to the highly concentrated fibrin sealant Tisseel, which delayed wound repair and possessed a higher fiber density. Conclusion: Collectively, we show that adding a tailored fibrin hydrogel scaffold to a wound bed positively influences the healing process, modulating leukocyte populations and inflammatory responses towards a faster wound repair.

Evaluation of general and sports nutritional knowledge of recreational athletes.

Background: Nutritional knowledge is one of the factors that can lead to adopting healthy eating habits and, consequently, favoring sports performance. Aim: The study aimed to assess the nutritional knowledge and its subsections general and sports nutritional knowledge of recreational athletes. Methods: A validated, translated, and adapted 35-item questionnaire was used to assess total (TNK), general-GNK (11 questions), and sports-SNK (24 questions) nutritional knowledge. The Abridged Nutrition for Sport Knowledge Questionnaire (ANSKQ) was provided online using Google Forms. Four hundred and nine recreational athletes (male: 173, female: 236, age = 32.4 ± 9.6 years) completed the questionnaire. Results: The mean TNK (50.7%) and GNK (62.7%) scores were classified as "average" and higher than SNK (45.2%), which was classified as "poor." Male participants had SNK and TNK scores higher than females, but not for GNK. The youngest participants (18-24 years) had TNK, SNK, and GNK scores higher than other age groups (p < 0.05). Participants who reported previous nutritional appointments with a nutritionist had higher TNK, SNK, and GNK scores than those without it (p < 0.05). Those with "advanced" formal nutrition education (university students, graduate, or postgraduate in Nutrition) scored higher than those of groups "none" and "intermediate," for TNK (advanced = 69.9%, intermediate = 52.9%, and none = 45.0%, p < 0.0001), GNK (advanced = 74.7%, intermediate = 63.8%, and none = 59.2%, p < 0.0001), and SNK, (advanced = 67.5%, intermediate = 48.0%, and none = 38.5%, p < 0.0001). Conclusion: Results suggest a lack of nutritional knowledge in recreational athletes, mainly those without an appointment with a registered nutritionist and formal nutritional education.

Matrix metalloproteinases in arthritis: towards precision medicine.

Proteolysis of structural molecules of the extracellular matrix (ECM) is an irreversible post-translational modification in all arthropathies. Common joint disorders, including osteoarthritis and rheumatoid arthritis, have been associated with increased levels of matrix remodelling enzymes, including matrix metalloproteinases (MMPs). MMPs, in concert with other host proteinases and glycanases, destroy proteoglycans, collagens and other ECM molecules. MMPs may also control joint remodelling indirectly by signalling through cell-surface receptors or by proteolysis of cytokines and receptor molecules. After synthesis as pro-forms, MMPs can be activated by various types of post-translational modifications, including proteolysis. Once activated, MMPs are controlled by general and specific tissue inhibitors of metalloproteinases (TIMPs). In rheumatoid arthritis, proteolysis of the ECM results in so-called remnant epitopes that enhance and perpetuate autoimmune processes in susceptible hosts. In osteoarthritis, the considerable production of MMP-13 by chondrocytes, often concurrent with mechanical overload, is a key event. Hence, information about the regulation, timing, localization and activities of MMPs in specific disease phases and arthritic entities will help to develop better diagnostics. Insights into beneficial and detrimental effects of MMPs on joint tissue inflammation are also necessary to plan and execute (pre)clinical studies for better therapy and precision medicine with MMP inhibitors. With the advances in proteomics and single-cell transcriptomics, two critical points need attention: neglected neutrophil MMP biology, and the analysis of net proteolytic activities as the result of balances between MMPs and their inhibitors.

Intrathoracic Kidney.

Intrathoracic kidney is a very rare finding, representing less than 5% of all renal ectopias. Because of the location of the liver, thoracic kidney on the right side is much less common than thoracic kidney on the left side. Although an increasing number of case reports are being published in the literature, few describe the impact of the ectopia on kidney function. We report the case of a woman with intrathoracic right kidney and chronic kidney disease that was initially misdiagnosed as pneumonia because of its presentation on chest x-ray. We highlight the need to including this condition in the differential diagnosis[2] as the literature rarely links it to changes in kidney function. LEARNING POINTS: Intrathoracic kidney is an extremely rare condition that should be considered in the differential diagnosis of intrathoracic masses.There is a lack of literature on this type of kidney ectopia and its consequences in asymptomatic individuals.

Dance of the Sugar: Two Case Reports of Chorea Associated With Nonketotic Hyperglycemia.

Hyperglycemia-induced chorea/ballism is a rare clinical entity that often occurs in the setting of nonketotic hyperglycemia due to poor glycemic control in elderly patients with a diagnosis of type 2 diabetes mellitus (DM). This condition is typically characterized by hemichorea/hemiballism and unique brain imaging findings in the contralateral basal ganglia. Treatment involves the correction of blood glucose, and most cases resolve without additional therapy. Here we report two cases of this condition in which patients with type 2 DM presented with nonketotic hyperglycemia and typical neuroimaging findings. Although rare, clinicians should be aware of this condition in patients with diabetes who present with sudden abnormal movements since its prompt diagnosis and treatment often lead to a favorable outcome.

AN 84-YEAR-OLD PATIENT WITH CAROLI SYNDROME: WHAT IS THE PROGNOSIS OF THIS CONDITION?

Caroli disease is a rare congenital pathology caused by mutation of the PKHD1 gene (polycystic kidney and hepatic disease 1), also responsible for autosomal recessive polycystic kidney disease. Characterized by segmental and multifocal dilatation of the large intrahepatic bile ducts, classic disease involves only malformation of the biliary tract. The association with congenital hepatic fibrosis is called Caroli syndrome. We describe the case of an 84-year-old man with Caroli syndrome diagnosed in 1997 by liver biopsy. The CT scan revealed massive hepatomegaly, extending to the pelvic region, and almost total replacement of the parenchyma by numerous cystic formations, no evidence of bile duct dilatation, and no ascites or splenomegaly suggestive of portal hypertension. The atypical clinical presentation, with no reported complications, resembles that of a space-occupying lesion with an indolent course, previously misdiagnosed as metastatic neoplasm. LEARNING POINTS: We describe a case of advanced and rare Caroli syndrome with an atypical clinical presentation of a space-occupying lesion with slow progression.The atypical presentation could be misdiagnosed as metastatic neoplasm.

Rectal Bezoar: A Rare Cause of Intestinal Obstruction.

Bezoars are conglomerates of undigested contents that accumulate in the gastrointestinal tract. They can have different compositions, such as fibers, seeds, vegetables (phytobezoars), hair (trichobezoars), and medication (pharmacobezoars). Bezoars are typically caused by an impaired grinding mechanism of the stomach or interdigestive migrating motor complex, but the composition of ingested material can also play a role in their formation. Gastric dysmotility, previous gastric surgery, and gastroparesis are some of the risk factors that can increase the likelihood of developing bezoars. While bezoars are usually asymptomatic and found in the stomach, they can sometimes migrate to the small intestine or colon and cause complications such as intestinal obstruction or perforation. Endoscopy is essential for diagnosis and etiology, and treatment depends on the composition, which can include chemical dissolution or surgical intervention. We present a case of an 86-year-old woman, who had a bezoar located in an unusual location (rectum), most likely due to migration. This condition led to symptoms of intermittent intestinal obstruction and rectal bleeding. However, due to anal stenosis, the patient was unable to expel the bezoar. Its removal was not possible through various endoscopic techniques. Therefore, it was removed via fragmentation, using an anoscope and forceps, due to its hard/stone-like consistency. This case highlights the importance of considering bezoars in the differential diagnosis of gastrointestinal bleeding and illustrates the importance of prompt diagnosis and appropriate techniques for the removal of bezoars.

Tumor Lysis Syndrome Rare Presentation As Uremic Pericarditis: A Case Report.

Tumor lysis syndrome (TLS) is an oncological emergency characterized by the massive destruction of malignant cells and the release of their contents into the extracellular space, which might occur spontaneously or post-chemotherapy. According to the Cairo&Bishop Classification, it can be defined by both laboratory criteria: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia (two or more); and clinical criteria: acute kidney injury (AKI), convulsions, arrhythmias, or death. We report the case of a 63-year-old man with a previous medical history of colorectal carcinoma and associated multiorgan metastasis. The patient was initially admitted to the Coronary Intensive Care Unit, five days after the chemotherapy session, on suspicion of Acute Myocardial Infarction. Upon admission, he presented without significant elevation of myocardial injury markers, but with laboratory abnormalities (hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia) and clinical symptoms (sudden sharp chest pain with pleuritic characteristics and electrocardiographic anomalies suggesting uremic pericarditis, and acute kidney injury), all consistent with TLS. The best approach to established TLS is aggressive fluid therapy and a decrease in uric acid levels. Rasburicase proved to be notoriously more effective, both in terms of prevention and treatment of established TLS, thus consisting of the first-line drug. However, in the present case, rasburicase was not available at the hospital level, so a decision was made to initiate treatment with allopurinol. The case evolved with slow but good clinical evolution. Its uniqueness resides in its initial presentation as uremic pericarditis, scarcely described in the literature. The constellation of metabolic alterations from this syndrome translates into a spectrum of clinical manifestations that can go unnoticed and ultimately may prove to be fatal. Its recognition and prevention are crucial for improving patient outcomes.

Junctional integrity and directional mobility of lymphatic endothelial cell monolayers are disrupted by saturated fatty acids.

The lymphatic circulation regulates transfer of tissue fluid and immune cells toward the venous circulation. While obesity impairs lymphatic vessel function, the contribution of lymphatic endothelial cells (LEC) to metabolic disease phenotypes is poorly understood. LEC of lymphatic microvessels are in direct contact with the interstitial fluid, whose composition changes during the development of obesity, markedly by increases in saturated fatty acids. Palmitate, the most prevalent saturated fatty acid in lymph and blood, is detrimental to metabolism and function of diverse tissues, but its impact on LEC function is relatively unknown. Here, palmitate (but not its unsaturated counterpart palmitoleate) destabilized adherens junctions in human microvascular LEC in culture, visualized as changes in VE-cadherin, α-catenin, and ß-catenin localization. Detachment of these proteins from cortical actin filaments was associated with abundant actomyosin stress fibers. The effects were Rho-associated protein kinase (ROCK)- and myosin-dependent, as inhibition with Y27632 or blebbistatin, respectively, prevented stress fiber accumulation and preserved junctions. Without functional junctions, palmitate-treated LEC failed to directionally migrate to close wounds in two dimensions and failed to form endothelial tubes in three dimensions. A reorganization of the lymphatic endothelial actin cytoskeleton may contribute to lymphatic dysfunction in obesity and could be considered as a therapeutic target.

A Rare Geriatric Diagnosis of Eosinophilic Granulomatosis With Polyangiitis: A Case Report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of systemic disease characterized by inflammation and necrotizing effects of the small and medium blood vessels. It is a vasculitis found in all age groups and both genders, although its etiology is unknown. The mean age at diagnosis is 40 years, consisting of an uncommon cause of vasculitis in people older than 65 years. It is the least common of the three antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis). The characteristic features of EGPA include extravascular eosinophilic granulomas, peripheral eosinophilia, and asthma, usually responsive to steroid treatment. In this article, we discuss a case of an 83-year-old male with a history of undetermined etiology of chronic kidney disease, chronic obstructive pulmonary disease (COPD), and severe chronic rhinosinusitis with nasal polyposis. First hospitalized with the suspicion of community-acquired pneumonia (CAP), based on worsening blood eosinophilia and unresolving respiratory symptoms, a suspicion for EGPA was raised. The development of an eosinophilic pleural effusion, later upon admission, was a predominant factor for its confirmation, as it constitutes a rare finding, only present in about 30% of patients. Laboratory tests showed elevated IgE, the presence of antineutrophil cytoplasmic antibodies directed against myeloperoxidase with a perinuclear staining pattern (ANCA-MPO), and the absence of antiproteinase 3 (anti-PR3) ANCA, which were consistent with the diagnosis. A pleural biopsy was then made, revealing fibrosis with the presence of eosinophils, although with no evidence of granulomas. According to the most recent and accepted classification criteria, the "2022 American College of Rheumatology and European Alliance of Associations for Rheumatology (ACR/EULAR) for EGPA," this patient presented with a score of 13 (a score greater than or equal to 6 is needed for the classification of EGPA). Hence, a diagnosis of EGPA was assumed, and the patient was initiated on corticosteroid therapy, with a favorable response. The aim of this article is to present a rare case of EGPA diagnosis made at the age of 83 years old, although there was evidence that could point to this disease years before the diagnosis was made. In the present case, it is important to point out the long diagnostic delay in a geriatric patient, much older than the median age of diagnosis for EGPA, culminating in a curious case of uncommon pleuroparenchymal involvement.

Quality of life of Brazilian families who have children with Williams syndrome.

This cross-sectional and descriptive study examined the family quality of life (FQoL) among 72 Brazilian families who have children with Williams syndrome, a rare genetic disorder in which most individuals have an intellectual disability, usually mild. Data were collected using sociodemographic and clinical data forms and the Beach Center FQoL Scale. The overall FQoL score was 3.90 ± 0.45, below the limit of four points considered satisfactory. Families felt more satisfied with the family interaction (4.11 ± 0.57), parenting (4.07 ± 0.42), and disability-related support (3.94 ± 0.62) domains, and less satisfied with the family's emotional (3.49 ± 0.73) and physical/material well-being (3.73 ± 0.74) domains. Paternal education, children's cardiopathy and autonomy in activities of daily living explained 24.5% of the variance in the overall FQoL. Measures are necessary to improve the emotional and physical/material well-being of families to reduce the family burden. Monitoring the child's cardiac condition and promoting independence in activities of daily living are also the main procedures.

N-(coumarin-3-yl)cinnamamide Promotes Immunomodulatory, Neuroprotective, and Lung Function-Preserving Effects during Severe Malaria.

Plasmodium berghei ANKA (PbA) infection in mice resembles several aspects of severe malaria in humans, such as cerebral malaria and acute respiratory distress syndrome. Herein, the effects of N-(coumarin-3-yl)cinnamamide (M220) against severe experimental malaria have been investigated. Treatment with M220 proved to protect cognitive abilities and lung function in PbA-infected mice, observed by an object recognition test and spirometry, respectively. In addition, treated mice demonstrated decreased levels of brain and lung inflammation. The production and accumulation of microglia, and immune cells that produce the inflammatory cytokines TNF and IFN-γ, decreased, while the production of the anti-inflammatory cytokine IL-10 by innate and adaptive immune cells was enhanced. Treatment with M220 promotes immunomodulatory, neuroprotective, and lung function-preserving effects during experimental severe malaria. Therefore, it may be an interesting therapeutic candidate to treat severe malaria effects.

Idiopathic pneumatosis cystoides coli: An uncommon cause of pneumoperitoneum.

Pneumatosis cystoides intestinalis (PCI) is a rare entity characterized by the presence of gaseous cystic within the intestinal wall. The primary or idiopathic type represents 15% of cases and is a self-limited or chronic benign entity. The secondary type represents 85% of cases and is associated with various factors, such as surgery, pharmacotherapy, chemotherapy, autoimmune diseases, inflammatory diseases, and pulmonary illness. Pneumatosis cystoides intestinalis affects the colon (pneumatosis cystoides coli) in about half of the cases. The differential diagnosis of PCI includes potentially life-threatening diseases that cause pneumatosis intestinalis. The misdiagnosis of PCI is common and can lead to unnecessary treatments and surgical procedures. We describe an asymptomatic pneumoperitoneum incidentally seen on chest radiograph. The cause was pneumatosis cystoides coli, which did not require treatment.

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.