Mechanism of high-mannose N-glycan breakdown and metabolism by Bifidobacterium longum.

Bifidobacteria are early colonizers of the human gut and play central roles in human health and metabolism. To thrive in this competitive niche, these bacteria evolved the capacity to use complex carbohydrates, including mammalian N-glycans. Herein, we elucidated pivotal biochemical steps involved in high-mannose N-glycan utilization by Bifidobacterium longum. After N-glycan release by an endo-ß-N-acetylglucosaminidase, the mannosyl arms are trimmed by the cooperative action of three functionally distinct glycoside hydrolase 38 (GH38) α-mannosidases and a specific GH125 α-1,6-mannosidase. High-resolution cryo-electron microscopy structures revealed that bifidobacterial GH38 α-mannosidases form homotetramers, with the N-terminal jelly roll domain contributing to substrate selectivity. Additionally, an α-glucosidase enables the processing of monoglucosylated N-glycans. Notably, the main degradation product, mannose, is isomerized into fructose before phosphorylation, an unconventional metabolic route connecting it to the bifid shunt pathway. These findings shed light on key molecular mechanisms used by bifidobacteria to use high-mannose N-glycans, a perennial carbon and energy source in the intestinal lumen.

Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding.

The nucleocapsid (N) protein of the SARS-CoV-2 virus, the causal agent of COVID-19, is a multifunction phosphoprotein that plays critical roles in the virus life cycle, including transcription and packaging of the viral RNA. To play such diverse roles, the N protein has two globular RNA-binding modules, the N- (NTD) and C-terminal (CTD) domains, which are connected by an intrinsically disordered region. Despite the wealth of structural data available for the isolated NTD and CTD, how these domains are arranged in the full-length protein and how the oligomerization of N influences its RNA-binding activity remains largely unclear. Herein, using experimental data from electron microscopy and biochemical/biophysical techniques combined with molecular modeling and molecular dynamics simulations, we show that, in the absence of RNA, the N protein formed structurally dynamic dimers, with the NTD and CTD arranged in extended conformations. However, in the presence of RNA, the N protein assumed a more compact conformation where the NTD and CTD are packed together. We also provided an octameric model for the full-length N bound to RNA that is consistent with electron microscopy images of the N protein in the presence of RNA. Together, our results shed new light on the dynamics and higher-order oligomeric structure of this versatile protein.

Carvacrol reduces blood pressure, arterial responsiveness and increases expression of MAS receptors in spontaneously hypertensive rats.

AIM: To analyze the effect of the use of carvacrol in the cardiovascular system of spontaneously hypertensive rats (SHR). METHODS: Methods: Twenty animals were allocated in four groups, one group control Wistar receiving only sorbitol, used as vehicle of administration of the carvacrol (Wistar-Vehicle), one control group SHR, also receive only sorbitol (SHR-Vehicle), a third, treated with losartan (SHR-Losartan/50 mg/kg), and the fourth, treated with carvacrol (SHR - Carvacrol/20 mg/kg). Sorbitol, losartan and carvacrol were administered by oral gavage daily for 30-day. Hemodynamic variables, vascular reactivity, biochemical parameters, and expression of Mas and AT1 receptors in kidney tissues were analyzed. RESULTS: SHR- Carvacrol group showed a maximal effect of inhibition of 56% in the curve of norepinephrine. The Emax of the curves with Ca2+ were smaller in the groups SHR-losartan (40.17%) and SHR-carvacrol (35.71%) when compared to the SHR-Vehicle. The carvacrol increased the expression of the MAS receptors in kidney tissue. CONCLUSION: Thirty days of treatment with carvacrol showed an antihypertensive effect associated with less peripheral vascular resistance. Also, treatment with carvacrol increased the expression of MAS receptors in kidney tissue.

Effect of treatment with carvacrol and aerobic training on cardiovascular function in spontaneously hypertensive rats.

NEW FINDINGS: What is the central question of this study? Can two non-drug therapies, carvacrol and aerobic physical training, together have additive effects on the reduction of cardiovascular risks and control of arterial hypertension? What is the main finding and its importance? The oral use of carvacrol (20 mg/kg/day) can control sustained hypertension in spontaneously hypertensive rats, and when this use is associated with aerobic physical training, there is a more pronounced effect on the reduction of blood pressure values, making these therapies an adjunct option in the drug treatment of hypertension. ABSTRACT: Systemic arterial hypertension is considered the foremost cardiovascular risk factor, and it is important to examine different therapies that help prevent and treat it, especially when associated with other cardiovascular risk factors. In this context, it is known that both carvacrol and aerobic physical training benefit the cardiovascular system. This study investigated the effects of treatment with carvacrol combined with aerobic exercise on hypertensive rats with cardiovascular risk parameters. We used an experimental design with six groups: normotensive control (Wistar rats); hypertensive control (spontaneously hypertensive rats, SHR); positive control rats treated with amlodipine (Aml-20 mg); rats treated with carvacrol (Carv-20 mg); rats trained with exercise (Exer); and rats treated with carvacrol and exercise (ExerCarv). The treatment lasted for 4 weeks, monitoring heart rate and systolic blood pressure (SBP). At the end of the treatment, vascular reactivity tests were performed in addition to biochemical measurements of urea, creatinine, aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, atherogenic indexes, relative heart weight and histopathological analysis of cardiac perivascular tissue. Significant reductions in SBP were observed after the training period, with the ExerCarv group showing a greater magnitude of reduction (∆SBP = 88 ± 10.0 mmHg, 42%). This group also experienced reductions in atherogenic indices and improvement in all analysed lipid parameters, with no differences observed in the Exer group. The findings indicated that the interaction between aerobic exercise and carvacrol offers a greater BP reduction. Exercise is particularly effective for controlling biochemical parameters of cardiovascular risk, regardless of carvacrol use.

Tailoring strength of nanocellulose foams by electrostatic complexation.

Supramolecular assembly of biobased components in water is a promising strategy to construct advanced materials. Herein, electrostatic complexation was used to prepare wet-resilient foams with improved mechanical property. Small-angle X-ray scattering and cryo-transmission electron microscopy experiments showed that suspensions with oppositely charged cellulose nanofibers are a mixture of clusters and networks of entangled fibers. The balance between these structures governs the colloidal stability and the rheological behavior of CNFs in water. Foams prepared from suspensions exhibited maximum compressive modulus at the mass composition of 1:1 (ca 0.12 MPa), suggesting that meaningful attractive interactions happen at this point and act as stiffening structure in the material. Besides the electrostatic attraction, hydrogen bonds and hydrophobic contacts may also occur within the clustering, improving the water stability of cationic foams. These results may provide a basis for the development of robust all- cellulose materials prepared in water, with nontoxic chemicals.

Visualization of supramolecular structure of Pluronic F127 micellar hydrogels using cryo-TEM.

Pluronic® F127 micellar hydrogels are of growing interest to the biomedical field due to their versatility as drug delivery systems. Pluronic® F127 is a symmetric and amphiphilic triblock copolymer which in aqueous medium self-assembles into micelles that pack togetherwith increasing temperature or concentration, leading to non-flowable hydrogels. The microstructure of these hydrogels is usually investigated by small-angle X-ray scattering, which is not a readily available technique. Conversely, cryo-TEM is a widespread technique used for investigating the morphology of aqueous systems. In the case of Pluronic® F127 micellar systems, the elevated viscosity poses a significant challenge for specimen preparation and, consequently, for cryo-TEM observation. Herein, we show a trustworthy, inexpensive and readily available methodology for preparing specimens of highly viscous micellar solutions and non-flowable hydrogels using an automated vitrification system. With this methodology we were able to visualize not only the morphology of individual Pluronic® F127 micelles -but also the supramolecular structure evolution as a function of concentration. This methodology opens up a wide range of opportunities for hydrogel characterization, although additional systematic studies might be required in order to optimize and replicate it for similar systems.

Clinical and Radiographic Evaluation of Patients Operated by the Bristow-Latarjet Technique with a Minimum Follow-Up of 20 Years.

Objective To verify the results of 27 patients submitted to surgery from 1990 to 1997 by the Bristow-Latarjet technique for the treatment of anterior traumatic instability of the shoulder. The analysis included the possible complications, especially the appearance of arthropathy. Methods The subjective clinical evaluation was performed through a questionnaire answered by the patients, and the objective evaluation was performed using the Rowe et al score. The radiographic evaluation was performed using the anteroposterior (true) incidence to detect signs of shoulder arthrosis, according to the classification of Samilson and Prieto, as well as the apical oblique and the Bernageau and Patte incidences to verify the consolidation of the bone graft, the position of the screw and of the graft, and signs of the release of the synthesis material. These evaluations were performed by two examiners at different times without interference between them. Results In the subjective assessment of the patients, 93% were fully recovered, and, in the objective evaluation, the average was 95 points on the Rowe et al score. Complications related to coracoid placement were not found. The degree of arthropathy of the shoulders, according to the Samilson and Prieto classification, presented an average of seven mild cases, two moderate cases and one severe case. In total, 17 patients did not present arthropathy. Conclusion Between the first and second evaluations, there was no change in the efficacy of the Bristow-Latarjet technique. The careful observation of the criteria of the technique was fundamental to avoid complications. The occurrence of arthropathy in the long term was not relevant in our evaluation. Based on the evidences of the present study, the surgical procedure alone is not the cause of the onset of the arthropathy, but the failure in its execution.

Clinical and Radiographic Evaluation of Patients Operated by the Bristow-Latarjet Technique with a Minimum Follow-Up of 20 Years / Avaliação clínica e radiográfica de pacientes operados pela técnica de Bristow-Latarjet com seguimento mínimo de 20 anos

Abstract Objective To verify the results of 27 patients submitted to surgery from 1990 to 1997 by the Bristow-Latarjet technique for the treatment of anterior traumatic instability of the shoulder. The analysis included the possible complications, especially the appearance of arthropathy. Methods The subjective clinical evaluation was performed through a questionnaire answered by the patients, and the objective evaluation was performed using the Rowe et al score. The radiographic evaluation was performed using the anteroposterior (true) incidence to detect signs of shoulder arthrosis, according to the classification of Samilson and Prieto, as well as the apical oblique and the Bernageau and Patte incidences to verify the consolidation of the bone graft, the position of the screw and of the graft, and signs of the release of the synthesis material. These evaluations were performed by two examiners at different times without interference between them. Results In the subjective assessment of the patients, 93% were fully recovered, and, in the objective evaluation, the average was 95 points on the Rowe et al score. Complications related to coracoid placement were not found. The degree of arthropathy of the shoulders, according to the Samilson and Prieto classification, presented an average of seven mild cases, two moderate cases and one severe case. In total, 17 patients did not present arthropathy. Conclusion Between the first and second evaluations, there was no change in the efficacy of the Bristow-Latarjet technique. The careful observation of the criteria of the technique was fundamental to avoid complications. The occurrence of arthropathy in the long term was not relevant in our evaluation. Based on the evidences of the present study, the surgical procedure alone is not the cause of the onset of the arthropathy, but the failure in its execution.

Resumo Objetivo Verificar os resultados do procedimento cirúrgico de 27 pacientes operados, durante o período de 1990 a 1997, pela técnica de Bristow-Latarjet para tratamento da instabilidade traumática anterior do ombro, considerando as possíveis complicações, e, principalmente, o aparecimento de artropatia. Métodos A avaliação clínica subjetiva foi realizada por meio de um questionário respondido pelos pacientes, e a avaliação objetiva foi feita mediante o escore de Rowe et al. A avaliação radiográfica foi realizada usando as incidências anterioposterior (verdadeira), para visualizar a presença de sinais de artrose do ombro, segundo a classificação de Samilson e Prieto, e oblíqua apical e de Bernageau e Patte, para verificar a consolidação do enxerto ósseo, o posicionamento do parafuso, do enxerto, e os sinais de soltura do material de síntese. Estas avaliações foram realizadas por dois examinadores em tempos diferentes, sem interferência entre eles. Resultados Na avaliação subjetiva dos pacientes, 93% estavam totalmente recuperados, e, na avaliação objetiva, a média foi de 95 pontos na escala de Rowe et al. Não foram encontradas as complicações relativas à colocação do enxerto de coracoide. O grau de artropatia dos ombros, de acordo com a classificação de Samilson e Prieto, apresentou uma média de sete casos suaves, dois casos moderados, e um caso grave. No total, 17 pacientes não apresentaram artropatia. Conclusão Entre a primeira e a segunda avaliações, não houve alteração quanto à eficácia da técnica de Bristow-Latarjet. A observação cuidadosa dos critérios da técnica foi fundamental para evitar complicações. A ocorrência de artropatia em longo prazo não foi relevante em nossa avaliação. Pelas evidências do presente estudo, somente o procedimento cirúrgico não é a causa do surgimento da artropatia, mas a falha na sua execução.

Essential oils as molluscicidal agents against schistosomiasis transmitting snails - a review.

This review aims to describe essential oils with bioactivity on adult snails of the genera Bulinus and Biomphalaria, which are intermediate hosts of schistosomes, and brings together information relating to the importance of molluscicides and the chemical composition and toxicity of such oils for other aquatic species. Analysis of the data of original articles revealed that 50 essential oils obtained from 46 plant species were evaluated for molluscicidal activity against the genera cited. More than 80% of the volatile oils studied were active, according to the criteria of the World Health Organization (LC90 or LC100 ≤100 µg/mL or LC50 <40 µg/mL), and most of the oils came from plants belonging to the Rutaceae, Lamiaceae and Pinaceae. Around 37% of the surveyed plant species were obtained in Brazil and 88% of these plants were collected in the northeast of the country, a region with a high prevalence of schistosomiasis mansoni. The essential oils with the highest toxicity against host snails had high levels of hydrocarbon monoterpenes and oxygenated monoterpenes, which may be responsible for the molluscicidal activity. Some volatile components were subjected to molluscicidal evaluation, and the monoterpene compounds exhibited a significant molluscicide effect. This review confirmed the importance of essential oils as a promising alternative for the development of natural molluscicide products. However, in order to be safe for use at sites where schistosome intermediate hosts are found, information on ecotoxicity is required and, to date, few oils have been tested against non-target aquatic species.

Chemical Characterization and Wound Healing Property of Jacaranda decurrens Cham. (Bignoniaceae): An Experimental Study Based on Molecular Mechanisms.

BACKGROUND: Jacaranda decurrens Cham., known as carobinha, is prevalent in the Cerrado biome and presents popular use in treatment of dermatological diseases. The present study aimed to investigate the healing action of topical formulation of Jacaranda decurrens Cham. (FtEHJ) in mice cutaneous lesions. METHODS: Phytochemical analysis of J. decurrens hydroalcoholic extract was carried out by using HPLC-PDA-ESI-MS and FIA-ESI-IT-MSn. Swiss mice were treated topically with formulation base (FtB) or Fibrinase® or ointment FtEHJ (15 mg/g; 50 mg/Kg). At the end of treatment periods, the inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the lesions were measured by using ELISA and gene expression of TGF-ß, Collagen I, and Collagen III was demonstrated by RTqPCR method and histological evaluation. RESULTS: Ten compounds were identified in the extract, distributed among the classes of flavonoids and triterpenes. Treatment with FtEHJ increased the wound contraction in 24 hours, such as reduction of TNF-α, IL-1ß, and IL-6 (pg/mL) cytokines in the lesion. The TGF-ß and collagen gene expression was increased and the wound closure accelerated to nine days, with discrete inflammation, collagenization, and accented reepithelialization. Conclusions. The results obtained suggest chemical compounds present in the FtEHJ accelerates wound healing by being a gene expression modulator, and protein content of different molecules are involved in tissue repair.

Hydroalcoholic extract of leaves of Arrabidaea brachypoda (DC. ) Bureau present antispasmodic activity mediated through calcium influx blockage

Aim: Since other species of the Bignoniaceae Family presented of antispasmodic activity, it was decided, by chemotaxonomic criterion, to determine the antispasmodic activity of the leaves of Arrabidaea brachypoda. Methodology: the segments of the rat jejunum were suspended in glass vats containing specific saline solution, at an appropriate temperature, and after stabilization period, were stimulated by a contractile agent to observe the inhibitory or relaxing effect of EH-FAB. Results: EH-FAB showed the presence of 10 compounds, mainly rutin and it has an antispasmodic activity as it inhibits the phasic component and relaxes the tonic component of the contraction in isolated rat jejunum. To assess the mechanism of antispasmodic action, cumulative curves to the CCh were performed in which a non-competitive antagonism was observed, due to a displacement of the control curve to the right and reduction of the maximum contraction effect (Emax). Afterward, the participation of the calcium and/or potassium channels was evaluated by increasing the extracellular potassium, and it was observed that the EH-FAB relaxed the rat jejunum, suggesting the participation of the Ca2+ channels. To corroborate that hypothesis, the EH-FAB was tested against cumulative curves to Ca2+ in a free depolarizing solution of Ca2+, and it was observed that there was a shift of the curve to the right with a reduction in Emax. Conclusions: EH-FAB presents antispasmodic activity in isolated rat jejunum and it is suggested to block the influx of Ca2+ through voltage-gated calcium channels, signaling the therapeutic potential for the treatment of colic and/or diarrhea.(AU)

From Inflammation to Current and Alternative Therapies Involved in Wound Healing.

Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.

Molecular studies with Aedes (Stegomyia) aegypti (Linnaeus, 1762), mosquito transmitting the dengue virus.

Dengue is an infectious viral disease, which can present a wide clinical picture, ranging from oligo or asymptomatic forms, to bleeding and shock, and can progress to death. The disease problem has increased in recent years, especially in urban and suburban areas of tropical and subtropical regions. There are five dengue viruses, called serotypes (DEN-1, DEN-2, DEN-3, DEN-4, and DEN-5), which belong to the Flaviviridae family and are transmitted to humans through infected mosquito bites, with the main vector the Aedes aegypti mosquito (Linnaeus, 1762). Studies performed with Ae. aegypti, aimed at their identification and analysis of their population structure, are fundamental to improve understanding of the epidemiology of dengue, as well for the definition of strategic actions that reduce the transmission of this disease. Therefore, considering the importance of such research to the development of programs to combat dengue, the present review considers the techniques used for the molecular identification, and evaluation of the genetic variability of Ae. aegypti.

Phytochemical Characterization of Terminalia catappa Linn. Extracts and Their antifungal Activities against Candida spp.

Terminalia catappa Linn bark is used to treat dysentery by various populations in Southeast Asian countries, and its leaves have also been used in traditional medicine to treat hepatitis in India and the Philippines. Here, the antifungal actions of crude hydro-alcoholic extract (TcHE) and fractions from T. catappa leaves were assessed via the agar diffusion and microdilution tests on Candida reference strains and clinical isolates from patients with acquired immunodeficiency syndrome (AIDS). Additionally, the potential cytotoxic effects of TcHE were assessed on cultured human peripheral blood mononuclear cells (PBMC). T. catappa fractions and sub-fractions were analyzed by gas chromatography coupled to mass spectrometry with electron impact (GC/MS/EI), high-performance liquid chromatography coupled to mass spectrometry "electrospray" ionization in positive mode (HPLC/MS/MS/ESI+) and hydrogen nuclear magnetic resonance (1HNMR). TcHE and its fractions were able to inhibit the growth of all tested Candida strains with the n-butanol (FBuOH) fraction presenting the best antifungal activity. Testing of different FBuOH sub-fractions (SF) showed that SF10 was the most active against Candida spp. Fractioning of SF10 demonstrated that 5 out of its 15 sub-fractions were active against Candida spp., with SF10.5 presenting the highest activity. Chemical analysis of SF10 detected hydrolysable tannins (punicalin, punicalagin), gallic acid and flavonoid C-glycosides. Overall, the results showed that T. catappa L. leaf extract, fractions and sub-fractions were antifungal against Candida spp. and may be useful to treat diseases caused by this fungus.

Antinociceptive and Anti-inflammatory Effects of Triterpenes from Pluchea quitoc DC. Aerial Parts.

BACKGROUND: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as "quitoco," "caculucage," "tabacarana" and "madre-cravo," is indicated for inflammatory conditions such as bronchitis, arthritis, and inflammation in the uterus and digestive system. OBJECTIVE: This study evaluated the analgesic and anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc aerial parts. MATERIALS AND METHODS: The triterpenes compounds ß-amyrin, taraxasterol and pseudo-taraxasterol in a mixture (T); ß-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture (Ta); ß-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with ß-amyrin, taraxasterol and pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception and inflammation. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing and tail-flick tests while leukocyte migration to the peritoneal cavity was used for anti-inflammatory profile. RESULTS: The oral administration of T or Tafe (40 mg/kg and 70 mg/kg) and Ta (70 mg/kg) to mice reduced acetic acid-induced writhing. The tail-flick response of mice was not affected by T or Tafe (40 mg/kg). T or Tafe (40 mg/kg) and Ta (70 mg/kg) also inhibited peritoneal leukocyte infiltration following the injection of carrageenan. CONCLUSION: The results demonstrate the anti-inflammatory and peripheral antinociceptive activity of the triterpenes ß-amyrin, taraxasterol, and pseudo-taraxasterol that were decreased when these were acetylated; while the acetylated triterpenes in mixture with myristyloxy triterpenes improved this activity. These compounds seem, at least in part, to be related to the plant's reported activity. SUMMARY: The mixtures of hydroxylated, acetylated, and myristate triterpenes isolated from hexanic extracts of Pluchea quitoc DC. were analyzed in the models of nociception and inflammation in mice. The results demonstrate the anti-inflammatory and peripheral antinociceptive activity of the triterpenes ß-amyrin, taraxasterol, and pseudo-taraxasterol. This study showed too that the activity of triterpenes may be decreased by their being acetylated, while the acetylated triterpenes in mixture with myristate triterpenes improved this activity.Abbreviations Used: T: Triterpenes compounds ß-amyrin, taraxasterol, and pseudo-taraxasterol in a mixture, Ta: Triterpenes compounds ß-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture, Tafe: Triterpenes compounds ß-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with ß-amyrin, taraxasterol and pseudo-taraxasterol myristates, Ctrl: Control, Indo: Indomethacin, Dexa: Dexamethasone, EtOAc: Ethyl acetate, MeOH: Methanol.

Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach.

Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC·HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS). Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease.

Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors.

Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: case report.

INTRODUCTION: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. CASE REPORT: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. DISCUSSION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. CONCLUSION: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report / Malformações fetais associadas ao uso de antagonista dos receptores de angiotensina II: Relato de Caso

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .

Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...