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ABSTRACT Objective: The objectives of this study were to describe the first pediatric case of cold agglutinin syndrome (CAS) triggered by human adenovirus and review the literature. Case description: This case report involves a previously healthy, 2½-year-old female child with human adenovirus isolated in a nasal swab. At 72 h after admission, the patient progressed to a severe episode of anemia (hemoglobin level: 2.6 g/dL). The laboratory findings were consistent with CAS. The patient received blood transfusion, vitamin supplementation, adequate hydration, and thermal protection. At her last follow-up, 1 year after her initial presentation, she remains clinically well without signs of hemolysis. Comments: While severe CAS is extremely uncommon in the pediatric emergency department, human adenovirus infection is a common illness in pediatrics. Recently, the adenovirus has been associated with new complications (acute hepatitis and fulminant liver failure). Pediatric physicians and hematologists should be aware of unusual evolution, signs, and symptoms of this infection that warrant more urgent medical attention. In this case, the hematologic complication suspicion was the key to early diagnosis and adequate management.
RESUMO Objetivo: Descrever o primeiro caso pediátrico de síndrome da crioaglutinina desencadeado por adenovírus humano e revisar a literatura. Descrição do caso: Paciente do sexo feminino, dois anos e seis meses, previamente hígida e diagnosticada com adenovírus humano isolado em swab nasal. Após 72 horas da admissão, a paciente evoluiu com quadro de anemia grave (hemoglobina de 2,6 g/dL). Os achados laboratoriais foram compatíveis com síndrome da crioaglutinina. A paciente recebeu transfusão de concentrado de hemácias, suplementação vitamínica, hidratação adequada e proteção térmica. Em seu último retorno ambulatorial, um ano após a apresentação inicial, permanecia clinicamente bem, sem sinais de hemólise. Comentários: Enquanto a síndrome da crioaglutinina grave é extremamente incomum na emergência pediátrica, a infecção por adenovírus humano é um quadro comum na infância. Recentemente, o adenovírus tem sido associado a novas complicações, e pediatras e hematologistas devem ficar atentos à possibilidade de uma evolução incomum dessa infecção e dos sinais e sintomas que possam necessitar de atenção urgente. No caso apresentado, a suspeita da complicação hematológica foi a chave para o diagnóstico precoce e seu manejo adequado.
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces a spectrum of clinical manifestations that depend on the immune response of the patient, i.e., from an asymptomatic form to an inflammatory response with multiorgan deterioration. In some cases, severe cases of SARS-CoV-2 are characterized by an excessive, persistent release of inflammatory mediators known as a cytokine storm. This phenomenon arises from an ineffective T helper (Th)-1 response, which is unable to control the infection and leads to a reinforcement of innate immunity, causing tissue damage. The evolution of the disease produced by SARS-CoV2, known as COVID-19, has been of interest in several research fields. Asthma patients have been reported to present highly variable outcomes due to the heterogeneity of the disease. For example, the Th2 response in patients with allergic asthma is capable of decreasing Th1 activation in COVID-19, preventing the onset of a cytokine storm; additionally, IL-33 released by damaged epithelium in the context of COVID-19 potentiates either Th1 or T2-high responses, a process that contributes to poor outcomes. IL-13, a T2-high inflammatory cytokine, decreases the expression of angiotensin converting enzyme-2 (ACE2) receptor, hindering SARS-CoV-2 entry; finally, poor outcomes have been observed in COVID-19 patients with severe neutrophilic asthma. In other contexts, the COVID-19 lockdown has had interesting effects on asthma epidemiology. The incidence of asthma in the most populated states in Mexico, including Tamaulipas, which has the highest asthma incidence in the country, showed similar tendencies independent of how strict the lockdown measures were in each state. As described worldwide for various diseases, a decrease in asthma cases was observed during the COVID-19 lockdown. This decrease was associated with a drop in acute respiratory infection cases. The drop in cases of various diseases, such as diabetes, hypertension or depression, observed in 2020 was restored in 2022, but not for asthma and acute respiratory infections. There were slight increases in asthma cases when in-person classes resumed. In conclusion, although many factors were involved in asthma outcomes during the pandemic, it seems that acute respiratory infection is intimately linked to asthma cases. Social distancing during remote learning, particularly school lockdown, appears to be an important cause of the decrease in cases.
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Asma , COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Síndrome de Liberación de Citoquinas/epidemiología , ARN Viral , Control de Enfermedades Transmisibles , Asma/epidemiologíaRESUMEN
OBJECTIVE: The objectives of this study were to describe the first pediatric case of cold agglutinin syndrome (CAS) triggered by human adenovirus and review the literature. CASE DESCRIPTION: This case report involves a previously healthy, 2½-year-old female child with human adenovirus isolated in a nasal swab. At 72 h after admission, the patient progressed to a severe episode of anemia (hemoglobin level: 2.6 g/dL). The laboratory findings were consistent with CAS. The patient received blood transfusion, vitamin supplementation, adequate hydration, and thermal protection. At her last follow-up, 1 year after her initial presentation, she remains clinically well without signs of hemolysis. COMMENTS: While severe CAS is extremely uncommon in the pediatric emergency department, human adenovirus infection is a common illness in pediatrics. Recently, the adenovirus has been associated with new complications (acute hepatitis and fulminant liver failure). Pediatric physicians and hematologists should be aware of unusual evolution, signs, and symptoms of this infection that warrant more urgent medical attention. In this case, the hematologic complication suspicion was the key to early diagnosis and adequate management.
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Adenovirus Humanos , Anemia , Femenino , Humanos , Niño , Adulto Joven , Adulto , Transfusión Sanguínea , Anemia/etiologíaRESUMEN
Asthma is a condition in which a person's airways become inflamed, narrowed, and produce greater amounts of mucus than normal. It can cause shortness of breath, chest pain, coughing, or wheezing. In some cases, symptoms may be exacerbated. Thus, the current study was designed to determine the mechanism of action of 6-aminoflavone (6-NH2F) in ex vivo experiments, as well as to determine its toxicity in acute and sub-chronic murine models. Tissues were pre-incubated with 6-NH2F, and concentration-response curves to carbachol-induced contraction were constructed. Therefore, tracheal rings pre-treated with glibenclamide, 2-aminopyridine, or isoproterenol were contracted with carbachol (1 µM), then 6-NH2F relaxation curves were obtained. In other sets of experiments, to explore the calcium channel role in the 6-NH2F relaxant action, tissues were contracted with KCl (80 mM), and 6-NH2F was cumulatively added to induce relaxation. On the other hand, tissues were pre-incubated with the test sample, and after that, CaCl2 concentration-response curves were developed. In this context, 6-NH2F induced significant relaxation in ex vivo assays, and the effect showed a non-competitive antagonism pattern. In addition, 6-NH2F significantly relaxed the contraction induced by KCl and CaCl2, suggesting a potential calcium channel blockade, which was corroborated by in silico molecular docking that was used to approximate the mode of interaction with the L-type Ca2+ channel, where 6-NH2F showed lower affinity energy when compared with nifedipine. Finally, toxicological studies revealed that 6-NH2F possesses pharmacological safety, since it did not produce any toxic effect in both acute and sub-acute murine models. In conclusion, 6-aminoflavone exerted significant relaxation through calcium channel blockade, and the compound seems to be safe.
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The susceptibility of meat and meat products (MP) to oxidation and microbial deterioration poses a risk to the nutritional quality, safety, and shelf life of the product. This analysis provides a brief overview of how bioactive compounds (BC) impact meat and MP preservation, and how they can be utilized for preservation purposes. The use of BC, particularly plant-based antioxidants, can reduce the rate of auto-oxidation and microbial growth, thereby extending the shelf life of MP. These BC include polyphenols, flavonoids, tannins, terpenes, alkaloids, saponins, and coumarins, which have antioxidant and antimicrobial properties. Bioactive compounds can act as preservatives and improve the sensory and physicochemical properties of MP when added under appropriate conditions and concentrations. However, the inappropriate extraction, concentration, or addition of BC can also lead to undesired effects. Nonetheless, BC have not been associated with chronic-degenerative diseases and are considered safe for human consumption. MP auto-oxidation leads to the generation of reactive oxygen species, biogenic amines, malonaldehyde (MDA), and metmyoglobin oxidation products, which are detrimental to human health. The addition of BC at a concentration ranging from 0.025 to 2.5% (w/w in powdered or v/w in oil or liquid extracts) can act as a preservative, improving color, texture, and shelf life. The combination of BC with other techniques, such as encapsulation and the use of intelligent films, can further extend the shelf life of MP. In the future, it will be necessary to examine the phytochemical profile of plants that have been used in traditional medicine and cooking for generations to determine their feasibility in MP preservation.
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Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAEPa) of P. australis was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAEPa significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAEPa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD50 of HAEPa was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAEPa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.
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BACKGROUND: Traditional production of dry salted shrimp enhances cholesterol oxidation and astaxanthin degradation in the product. The aim of this study was to evaluate the effect of addition of the antioxidants butylhydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ) to cooked shrimp on the formation of cholesterol oxidation products (COPs) and astaxanthin degradation during solar drying of shrimp. RESULTS: The added antioxidants significantly inhibited COPs formation after the product was boiled in brine. Smaller amounts of COPs were formed in antioxidant-treated shrimps (~-23%) as compared to untreated samples. The antioxidants continued to significantly inhibit COPs formation (~-39%) during sun drying. Similarly, TBHQ and BHT reduced by 51.3% and 37.2%, respectively, the degradation rate of astaxanthin, favoring a higher retention of this carotenoid in the final product. CONCLUSION: The use of the antioxidants BHT and TBHQ in the preparation of dry salted shrimp significantly inhibited the formation of COPs after cooking raw shrimp and during direct solar drying. They also protected astaxanthin contained in the cooked shrimp from photodegradation. These results are technologically relevant because it is possible to prepare a product with a higher content of astaxanthin and lower the presence of hazardous COPs. © 2022 Society of Chemical Industry.
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Antioxidantes , Hidroquinonas , Antioxidantes/farmacología , Antioxidantes/química , ColesterolRESUMEN
ABSTRACT Objective: The objectives of this study were to describe the first pediatric case of cold agglutinin syndrome (CAS) triggered by human adenovirus and review the literature. Case description: This case report involves a previously healthy, 2½-year-old female child with human adenovirus isolated in a nasal swab. At 72 h after admission, the patient progressed to a severe episode of anemia (hemoglobin level: 2.6 g/dL). The laboratory findings were consistent with CAS. The patient received blood transfusion, vitamin supplementation, adequate hydration, and thermal protection. At her last follow-up, 1 year after her initial presentation, she remains clinically well without signs of hemolysis. Comments: While severe CAS is extremely uncommon in the pediatric emergency department, human adenovirus infection is a common illness in pediatrics. Recently, the adenovirus has been associated with new complications (acute hepatitis and fulminant liver failure). Pediatric physicians and hematologists should be aware of unusual evolution, signs, and symptoms of this infection that warrant more urgent medical attention. In this case, the hematologic complication suspicion was the key to early diagnosis and adequate management.
RESUMO Objetivo: Descrever o primeiro caso pediátrico de síndrome da crioaglutinina desencadeado por adenovírus humano e revisar a literatura. Descrição do caso: Paciente do sexo feminino, dois anos e seis meses, previamente hígida e diagnosticada com adenovírus humano isolado em swab nasal. Após 72 horas da admissão, a paciente evoluiu com quadro de anemia grave (hemoglobina de 2,6 g/dL). Os achados laboratoriais foram compatíveis com síndrome da crioaglutinina. A paciente recebeu transfusão de concentrado de hemácias, suplementação vitamínica, hidratação adequada e proteção térmica. Em seu último retorno ambulatorial, um ano após a apresentação inicial, permanecia clinicamente bem, sem sinais de hemólise. Comentários: Enquanto a síndrome da crioaglutinina grave é extremamente incomum na emergência pediátrica, a infecção por adenovírus humano é um quadro comum na infância. Recentemente, o adenovírus tem sido associado a novas complicações, e pediatras e hematologistas devem ficar atentos à possibilidade de uma evolução incomum dessa infecção e dos sinais e sintomas que possam necessitar de atenção urgente. No caso apresentado, a suspeita da complicação hematológica foi a chave para o diagnóstico precoce e seu manejo adequado.
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This study determined the effect of feeding Moringa oleifera (MO) leaf extracts to lactating ewes on the physicochemical composition of their milk and yogurt during storage (4 °C for 14 days) and the sensory acceptance of the yogurt. Over 45 days, 24 multiparous lactating Pelibuey and Katahdin ewes (two days in lactation) were randomly assigned to four groups: MO-0, basal diet (BD) + 0 mL MO; MO-20, BD + 20 mL MO; MO-40, BD + 40 mL MO; and MO-60, BD + 60 mL MO. In the milk, an increase of 6% in protein, 26% in leucine, 14% in ash, and 1% in the pH (6.71) was observed with MO-60. The density values decreased by 0.3% at a higher dose of MO compared to MO-0, while the nonfat solids (NFS) in the milk were similar between the treatments. In the yogurt, an increase of 5% in protein, 113% in leucine (MO-20), 9% in NFS, and a reduction of 2% in moisture with MO-60 was observed. The acidity reflected an inverse relationship to the pH, as did the moisture and NFS with MO-60. In conclusion, dietary supplementation with MO in lactating ewes did not have negative effects on the chemical composition of their yogurt during storage (14 days). Overall, feeding sheep with 20 mL of MO positively influenced the physicochemical composition of their milk and yogurt during storage.
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Difficult-to-treat asthma refers to asthma that is not controlled despite high or medium doses of inhaled steroids or in which high doses of treatment are required to maintain an adequate control of the symptoms and to reduce the risk of exacerbations. An inadequate technique to use the inhaler, poor adherence to treatment, smoking, comorbidities, or an incorrect diagnosis should be considered. In severe asthma, despite adherence to treatment with optimized maximum doses and the management of factors that could contribute, multiple medications in maximum doses are required to have an adequate therapeutic control or this is not achieved. The approach to these patients involves a meticulous process due to the multiple factors that can influence poor asthma control and that can lead to a misclassification of the disease when, in reality, the patient can be presenting different comorbidities whose treatment could decrease the severity of asthma symptoms and modify the prognosis. The objective of this document is to make the approach to patients with difficult-to-treat asthma and severe asthma known, as well as the most frequent comorbidities. A search was made in PubMed with the purpose of identifying the main pathologies that may be present in patients and, based on what is described in the literature, to propose a diagnostic approach. 100 studies were comprised in this review, including clinical guidelines such as GINA, GEMA, and ERS/ATS.
El asma difícil de tratar es la que no se controla a pesar de las dosis altas o medias de esteroides inhalados o la que requiere altas porciones para mantener un control adecuado de los síntomas y reducir el riesgo de exacerbaciones. Se deben tener en cuenta las fallas en la técnica del uso del inhalador, la pobre adherencia al tratamiento, el tabaquismo, las comorbilidades o el diagnóstico incorrecto. En el asma grave, a pesar de la adherencia al tratamiento con dosis optimizadas y el manejo de los factores contribuyentes, se requieren múltiples medicamentos en dosis máximas para tener un adecuado control, si no es así este no se logra. La dirección de estos pacientes implica un proceso minucioso, dados los múltiples factores que pueden influir en el mal control del asma y que pueden llevar a una inadecuada clasificación de la enfermedad, cuando en realidad puedan estar cursando con diferentes comorbilidades cuyo tratamiento puede disminuir la severidad de los síntomas del asma y modificar el pronóstico. El objetivo de esta investigación es dar a conocer el manejo de los pacientes con asma difícil de tratar y asma grave, así como las comorbilidades más frecuentes. Se realizó una búsqueda en Pubmed con el propósito de identificar las principales patologías que puedan estar presentes y, con base en la literatura, proponer un abordaje diagnóstico. Se incluyeron 100 estudios, incluidas las guías clínicas GINA, GEMA y ERS/ATS.
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Antiasmáticos , Asma , Administración por Inhalación , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/epidemiología , Comorbilidad , HumanosRESUMEN
PDZ (postsynaptic density (PSD95), discs large (Dlg), and zonula occludens (ZO-1)-dependent interactions are widely distributed within different cell types and regulate a variety of cellular processes. To date, some of these interactions have been identified as targets of small molecules or peptides, mainly related to central nervous system disorders and cancer. Recently, the knowledge of PDZ proteins and their interactions has been extended to various cell types of the immune system, suggesting that their targeting by viral pathogens may constitute an immune evasion mechanism that favors viral replication and dissemination. Thus, the pharmacological modulation of these interactions, either with small molecules or peptides, could help in the control of some immune-related diseases. Deeper structural and functional knowledge of this kind of protein-protein interactions, especially in immune cells, will uncover novel pharmacological targets for a diversity of clinical conditions.
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Dominios PDZ/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Animales , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Enfermedades del Sistema Inmune/tratamiento farmacológico , Enfermedades del Sistema Inmune/etiología , Enfermedades del Sistema Inmune/metabolismo , Modelos Moleculares , Terapia Molecular Dirigida , Péptidos/uso terapéutico , Unión Proteica/efectos de los fármacos , Conformación Proteica , Relación Estructura-ActividadRESUMEN
The influence of nano-emulsified curcumin (NEC) added to the hair sheep milk, prior to cheese-making, on the chemical composition, lipolysis, and proteolysis of manchego-style cheeses were evaluated throughout 80 days of ripening. The addition of NEC to the milk resulted in cheeses with the same moisture content (42.23%), total protein (23.16%), and water activity (0.969) (p > 0.05). However, it increased the fat and ash levels from 26.82% and 3.64% in B 10 ppm to 30.08% and 3.85% in C 10 ppm, respectively, at the end of the ripening (p < 0.05). The total phenolic content and antioxidant activity of experimental cheeses increased during ripening, and the fatty acid groups showed significant changes occurred to a greater extent in the first days of ripening (p < 0.05). The lipolysis increased consistently in all cheeses until day 40 of ripening, to decrease at the end, while proteolysis increased during all ripening time in all samples (p < 0.05); the addition of NEC did not alter the primary proteolysis of manchego-style cheeses, but it modified secondary proteolysis and lipolysis (p < 0.05). Principal component analysis was useful for discriminating cheeses according to their chemical composition and classified into four groups according to their ripening time. This research highlights the potential of CNE to fortify dairy foods to enhance their functionality.
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The content of gonadotropin-releasing hormone (GnRH), its mRNA, and estrogen receptor alpha (ERα) and beta (ERß) in the hypothalamus varies throughout the estrous cycle. Furthermore, the abundance of these molecules displays asymmetry between the right and left side. In the present study, we investigated the changes in the content of ERα, ERß, kisspeptin, and GnRH by western blot in the left and right anteromedial hypothalamus, at four different times during each stage of the rat estrous cycle. The serum levels of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also measured. ERα and ERß levels changed depending on the stage of the estrous cycle, meanwhile that of kisspeptin was modified according to both the hour of the day and the stage of the cycle. Except in estrus day, ERß was higher in the right hypothalamus, while ERα was similar in both sides. During both proestrus and estrus, the content of kisspeptin and GnRH was higher in the right hypothalamus. The highest levels of FSH and LH occurred at 17:00 h of proestrus. But at estrus, the highest FSH levels were observed at 08:00 h and the lowest at 17:00 h. Thus, the current results show that the content of ERα, ERß, kisspeptin, and GnRH in the anteromedial hypothalamus are regulated as a function of the stage of the estrous cycle and the hour of the day. Furthermore, the content of these proteins is regularly higher in the right anteromedial hypothalamus, regardless of the stage of the cycle or time of the day.
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Ciclo Estral/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Kisspeptinas/metabolismo , Receptores de Estrógenos/metabolismo , Animales , Femenino , RatasRESUMEN
We examined the role of the estrogen receptors alpha (ERα) and beta (ERß) in of the preoptic-anterior hypothalamic area (POA-AHA) in the regulation of ovulation in rats. The number of ERα- and ERß-immunoreactive (-ir) cells was determined at 09:00, 13:00, and 17:00 h of each stage of the estrous cycle in intact rats. Additionally, the effects of blocking ERα and ERß on ovulation rate at 09:00 h on diestrus-2 or proestrus day through the microinjection of methyl-piperidino-pyrazole (MPP) or cyclofenil in either side of POA-AHA were evaluated. The number of ERα-ir and ERß-ir cells in POA-AHA varied in each phase of estrous cycle. Either MPP or cyclofenil in the right side of POA-AHA on diestrus-2 day reduced the ovulation rate, while at proestrus day it was decreased in rats treated in either side with MPP, and in those treated with cyclofenil in the left side. MPP or cyclofenil produced a decrease in the surge of luteinizing hormone levels (LH) and an increase in progesterone and follicle stimulating hormone (FSH). Replacement with synthetic luteinizing hormone-releasing hormone in non-ovulating rats treated with MPP or cyclofenil restored ovulation. These results suggest that activation of estrogen receptors on the morning of diestrus-2 and proestrus day asymmetrically regulates ovulation and appropriately regulates the secretion of FSH and progesterone in the morning and afternoon of proestrus day. This ensures that both, the preovulatory secretion of LH and ovulation, occur at the right time.
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Núcleo Hipotalámico Anterior/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Ovulación , Área Preóptica/metabolismo , Animales , Núcleo Hipotalámico Anterior/efectos de los fármacos , Estradiol/sangre , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor beta de Estrógeno/antagonistas & inhibidores , Ciclo Estral/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ovulación/efectos de los fármacos , Óvulo/efectos de los fármacos , Óvulo/metabolismo , Área Preóptica/efectos de los fármacos , Progesterona/sangre , RatasRESUMEN
Previously, we described tracheal rat rings relaxation by several flavonoids, being 6-hydroxyflavone (6-HOF) the most active derivative of the series. Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti-asthmatic effect was assayed in in vivo OVAlbumin (OVA)-sensitized guinea pigs. Finally, the toxicological profile of 6-HOF was studied based on Organization of Economic Cooperation and Development guidelines with modifications. 6-HOF-induced relaxation appears to be related with receptor-operated calcium channel and voltage-operated calcium channel blockade as the main mechanism of action, and also through the production of relaxant second messengers NO and cGMP. Molecular docking supports that 6-HOF acts as calcium channel blocker and by activation of nitric oxide synthase. In addition, the in vivo anti-asthmatic experiments demonstrate the dose-dependent significant anti-allergic effect of 6-HOF induced by OVA, with best activity at 50 /kg. Finally, toxicological studies determined a LD50 > 2,000 mg/kg and, after 28 day of treatment with 6-HOF (50 mg/kg) by intragastric route, mice did not exhibit evidence of any significant toxicity. In conclusion, experiments showed that 6-HOF exerts significant relaxant activity through calcium channel blockade, and possibly, by NO/cGMP-system stimulation on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways. In addition, the flavonoid shows potential anti-asthmatic properties in an anti-allergic pathway. Furthermore, because the pharmacological and safety evidence, we propose this flavonoid as lead for the development of a novel therapeutic agent for the treatment of asthma and related respiratory diseases.
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Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Tráquea/efectos de los fármacos , Alérgenos/inmunología , Animales , Asma/fisiopatología , Canales de Calcio Tipo L/metabolismo , Cobayas , Técnicas In Vitro , Masculino , Ratones Endogámicos ICR , Simulación del Acoplamiento Molecular , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ovalbúmina/inmunología , Ratas Wistar , Pruebas de Toxicidad , Tráquea/fisiologíaRESUMEN
Curcumin is the main and most abundant bioactive component in Curcuma longa L. with documented properties in the prevention and treatment of chronic degenerative and infectious diseases. However, curcumin has low solubility in aqueous media, hence low bioavailability when administered orally. The use of nanoemulsions as carriers can provide a partial solution to bioavailability restrictions. In our study, O/W nanoemulsions of curcumin were prepared using lysophosphatidylcholine, a phospholipid with proven emulsification capacity; nevertheless, such qualities have not been previously reported in the preparation of nanoemulsions. Lysophosphatidylcholine was obtained by enzymatic removal of one fatty acid residue from phosphatidylcholine. The objective of our work was to formulate stable curcumin nanoemulsions and evaluate their bioavailability in BALB/c mice plasma after oral administration. Formulated nanoemulsions had a droplet size mean of 154.32 ± 3.10 nm, a polydispersity index of 0.34 ± 0.07 and zeta potential of -10.43 ± 1.10 mV; stability was monitored for 12 weeks. Lastly, in vivo pharmacokinetic parameters, using BALB/c mice, were obtained; namely, Cmax of 610 ± 65.0 µg mL-1 and Tmax of 2 h. Pharmacokinetic data revealed a higher bioavailability of emulsified as opposed to free curcumin. Research regarding other potential emulsifiers that may provide better health benefits and carry nano-encapsulated bioactive compounds more effectively, is necessary. This study provides important data on the preparation and design of nanoencapsulated Curcumin using lysophosphatidylcholine as an emulsifier.
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Curcumina/química , Composición de Medicamentos/métodos , Emulsionantes/química , Lisofosfatidilcolinas/química , Animales , Disponibilidad Biológica , Composición de Medicamentos/instrumentación , Emulsiones/química , Ratones , Nanopartículas/química , Tamaño de la Partícula , SolubilidadRESUMEN
Abstract Introduction: In teenagers with perennial allergic rhinitis, exposure to tobacco cigarette smoke increases the count of eosinophils in the nasal mucosa; the recruitment of eosinophils arises from the combined action of a number of cellular and molecular signals, including eotaxin. Objective: To assess the effect of exposure to tobacco cigarette smoke on the count of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa of children and teenagers with perennial allergic rhinitis. Methods: In a cross-sectional study, forty-four patients were evaluated (aged 7-19 years old): 22 with and 22 with no exposure to tobacco cigarette smoke. After replying to 2 validated questionnaires, on Asthma and Allergies in Childhood and on the severity of nasal symptoms, nasal mucosal samples were obtained by scraping the middle one-third of the inferior turbinates. Then counts of immunoreactive cells to eotaxin-1 and eosinophils were assessed by immunohistochemistry. Results: Patients with exposure to tobacco cigarette smoke showed higher cell counts of both eotaxin-1 and eosinophils than patients with no exposure to the smoke, with no correlation between the two variables. However, both counts, of eotaxin-1 and eosinophils, were related to the cotinine/creatinine ratio. Conclusions: Exposure to tobacco cigarette smoke can increase eotaxin-1 and the count of eosinophils in the nasal mucosa of young patients with perennial allergic rhinitis.
Resumo Introdução: Em adolescentes com rinite alérgica perene, a exposição à fumaça do cigarro de tabaco aumenta a contagem de eosinófilos na mucosa nasal. O recrutamento de eosinófilos surge da ação combinada de alguns sinais celulares e moleculares, inclusive a eotaxina. Objetivo: Avaliar o efeito da exposição à fumaça do cigarro de tabaco na contagem de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal de crianças e adolescentes com rinite alérgica perene. Método: Em um estudo transversal, 44 pacientes foram avaliados (entre sete e 19 anos): 22 com e 22 sem exposição à fumaça do cigarro de tabaco. Depois de responder a dois questionários validados, sobre asma e alergias na infância e sobre a gravidade dos sintomas nasais, as amostras de mucosa nasal foram obtidas por meio de raspagem do terço médio das conchas inferiores. Em seguida, as contagens de células imunorreativas para eotaxina-1 e eosinófilos foram avaliadas por imuno-histoquímica. Resultados: Os pacientes com exposição à fumaça do cigarro de tabaco apresentaram contagens de células mais elevadas tanto para eotaxina-1 como para eosinófilos em comparação com os pacientes sem exposição à fumaça, sem correlação entre as duas variáveis. No entanto, ambas as contagens, de eotaxina-1 e eosinófilos foram relacionadas com a razão cotinina/creatinina. Conclusões: A exposição à fumaça do cigarro de tabaco pode aumentar a eotaxina-1 e a contagem de eosinófilos na mucosa nasal de pacientes jovens com rinite alérgica perene.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Adulto Joven , Contaminación por Humo de Tabaco/efectos adversos , Rinitis Alérgica Estacional/inmunología , Eosinófilos/inmunología , Quimiocina CCL11/inmunología , Mucosa Nasal/inmunología , Índice de Severidad de la Enfermedad , Inmunohistoquímica , Recuento de Células , Rinitis Alérgica Estacional/patología , Estudios Transversales , Eosinófilos/citología , Quimiocina CCL11/análisis , Mucosa Nasal/citología , Mucosa Nasal/químicaRESUMEN
Muscarinic receptors types 1 (m1AChR) and 2 (m2AChR) in the preoptic and anterior hypothalamus areas (POA-AHA) were counted, and the effects of blocking these receptors on spontaneous ovulation were analysed throughout the rat oestrous cycle. Rats in each phase of the oestrous cycle were assigned to the following experiments: (1) an immunohistochemical study of the number of cells expressing m1AChR or m2AChR in the POA-AHA and (2) analysis of the effects of the unilateral blockade of the m1AChR (pirenzepine, PZP) or m2AChR (methoctramine, MTC) on either side of the POA-AHA on the ovulation rate. The number of m2AChR-immunoreactive cells was significantly higher at 09:00 h on each day of the oestrous cycle in the POA-AHA region, while no changes in the expression profile of m1AChR protein were observed. The ovulation rate in rats treated with PZP on the oestrous day was lower than that in the vehicle group. Animals treated on dioestrous-1 with PZP or MTC had a higher ovulation rate than those in the vehicle group. In contrast, on dioestrous-2, the MTC treatment decreased the ovulation rate. These results suggest that m1AChR or m2AChR in the POA-AHA could participate in the regulation of spontaneous ovulation in rats.
RESUMEN
BACKGROUND: Curcumin is a natural, oil-soluble polyphenolic compound with potent anticancer, anti-inflammatory, and antioxidant activities. In its free form, it is very poorly absorbed in the gut due to its very low solubility. The use of nanoemulsions as carrier is a feasible way for improving curcumin bioavailability. To this end, the choice of emulsifying agent for stabilizing the nanoemulsions is of the upmost importance for achieving a desired functionality. METHODS: Phosphatidylcholine (PC) and phosphatidycholine enriched (PCE) with medium chain fatty acids (42.5 mol %) in combination with glycerol as co-surfactant, were used for preparing oil-in water nanoemulsions coded as NEPC and NEPCE, respectively. RESULTS: NEPCE displayed significantly smaller mean droplet size (30 nm), equal entrapment efficiency (100%), better droplet stability and suffered lower encapsulation efficiency loss (3%) during storage time (120 days, 4ºC) than NEPC. Bioavailability, measured in terms of area under the curve of curcumin concentration versus time, and maximum curcumin plasma concentration, was in general terms significantly higher for NEPCE than for NEPC, and for curcumin coarse aqueous suspension (CCS). Also, NEPCE produced significantly higher curcumin concentrations in liver and lung than NEPC and CCS. CONCLUSION: These data support the role of phosphatidylcholine enriched with medium chain fatty acids to increase the bioavailability of nanoemulsions for therapeutic applications.
Asunto(s)
Disponibilidad Biológica , Curcumina/farmacología , Ácidos Grasos/química , Fosfatidilcolinas/química , Animales , Emulsiones/química , Masculino , Ratones Endogámicos BALB C , Nanopartículas , Tamaño de la PartículaRESUMEN
INTRODUCTION: In teenagers with perennial allergic rhinitis, exposure to tobacco cigarette smoke increases the count of eosinophils in the nasal mucosa; the recruitment of eosinophils arises from the combined action of a number of cellular and molecular signals, including eotaxin. OBJECTIVE: To assess the effect of exposure to tobacco cigarette smoke on the count of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa of children and teenagers with perennial allergic rhinitis. METHODS: In a cross-sectional study, forty-four patients were evaluated (aged 7-19 years old): 22 with and 22 with no exposure to tobacco cigarette smoke. After replying to 2 validated questionnaires, on Asthma and Allergies in Childhood and on the severity of nasal symptoms, nasal mucosal samples were obtained by scraping the middle one-third of the inferior turbinates. Then counts of immunoreactive cells to eotaxin-1 and eosinophils were assessed by immunohistochemistry. RESULTS: Patients with exposure to tobacco cigarette smoke showed higher cell counts of both eotaxin-1 and eosinophils than patients with no exposure to the smoke, with no correlation between the two variables. However, both counts, of eotaxin-1 and eosinophils, were related to the cotinine/creatinine ratio. CONCLUSIONS: Exposure to tobacco cigarette smoke can increase eotaxin-1 and the count of eosinophils in the nasal mucosa of young patients with perennial allergic rhinitis.