Time of day affects MrgD-dependent modulation of cardiomyocyte contractility.

The renin-angiotensin system (RAS) is composed of a series of peptides, receptors, and enzymes that play a pivotal role in maintaining cardiovascular homeostasis. Among the most important players in this system are the angiotensin-II and angiotensin-(1-7) peptides. Our group has recently demonstrated that alamandine (ALA), a peptide with structural and functional similarities to angiotensin-(1-7), interacts with cardiomyocytes, enhancing contractility via the Mas-related G protein-coupled receptor member D (MrgD). It is currently unknown whether this modulation varies along the distinct phases of the day. To address this issue, we assessed the ALA-induced contractility response of cardiomyocytes from mice at four Zeitgeber times (ZTs). At ZT2 (light phase), ALA enhanced cardiomyocyte shortening in an MrgD receptor-dependent manner, which was associated with nitric oxide (NO) production. At ZT14 (dark phase), ALA induced a negative modulation on the cardiomyocyte contraction. ß-Alanine, an MrgD agonist, reproduced the time-of-day effects of ALA on myocyte shortening. NG-nitro-l-arginine methyl ester, an NO synthase inhibitor, blocked the increase in fractional shortening induced by ALA at ZT2. No effect of ALA on myocyte shortening was observed at ZT8 and ZT20. Our results show that ALA/MrgD signaling in cardiomyocytes is subject to temporal modulation. This finding has significant implications for pharmacological approaches that combine chronotherapy for cardiac conditions triggered by disruption of circadian rhythms and hormonal signaling.NEW & NOTEWORTHY Alamandine, a member of the renin-angiotensin system, serves critical roles in cardioprotection, including the modulation of cardiomyocyte contractility. Whether this effect varies along the day is unknown. Our results provide evidence that alamandine via receptor MrgD exerts opposing actions on cardiomyocyte shortening, enhancing, or reducing contraction depending on the time of day. These findings may have significant implications for the development and effectiveness of future cardiac therapies.

Genetic variations in immune mediators and prostate cancer risk: A field synopsis with Bayesian calculations.

OBJECTIVE: Our study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. METHODS: We performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein-protein networks were designed for the genes and products enrolled in the results. RESULTS: As results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein-protein networks reinforced the findings on IL1B and IL18 genes. CONCLUSION: In conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

Synergism in Two-Component Insecticides with Dillapiole against Fall Armyworm.

The fall armyworm (Spodoptera frugiperda), a polyphagous insect pest, is a major threat to food production, rapidly spreading through all the tropical areas in the world. Resistance has developed to the control protocols used so far (pyrethroids, organophosphorus, and genetically modified plants), and alternative strategies must be found. The bioactivity in essential oils is usually associated with the major constituents, but synergistic interactions among the constituents (even minor ones) can improve the levels of activity considerably. Herein, we tested the insecticidal activity of several constituents of the essential oil from Piper aduncum, an Amazonian Piperaceae, both separately and as binary mixtures, through their application on the dorsal side of the larva pronotum. Dillapiole proved to be, isolated, the most active compound in this oil (LD50 = 0.35 ppm). In binary mixtures, a strong synergistic effect was observed for the pairs of dillapiole with ß-caryophyllene (LD50 = 0.03 ppm), methyl eugenol (LD50 = 0.05 ppm), and α-humulene (LD50 = 0.05 ppm). In some cases, however, antagonism was recorded, as for dillapiole + ß-pinene (LD50 = 0.44 ppm). The use of binary mixtures of essential oil constituents as low-environmental-toxicity insecticides allows a fine tuning of the insecticidal activity, and the exploitation of synergy effects.

Cardiac disturbances and changes in tissue cytokine levels in mice fed with a high-refined carbohydrate diet.

AIMS: The consumption of highly refined carbohydrates increases systemic inflammatory markers, but its potential to exert direct myocardial inflammation is uncertain. Herein, we addressed the impact of a high-refined carbohydrate (HC) diet on mice heart and local inflammation over time. MAIN METHODS: BALB/c mice were fed with a standard chow (control) or an isocaloric HC diet for 2, 4, or 8 weeks (HC groups), in which the morphometry of heart sections and contractile analyses by invasive catheterization and Langendorff-perfused hearts were assessed. Cytokines levels by ELISA, matrix metalloproteinase (MMP) activity by zymography, in situ reactive oxygen species (ROS) staining and lipid peroxidation-induced TBARS levels, were also determined. KEY FINDINGS: HC diet fed mice displayed left ventricular hypertrophy and interstitial fibrosis in all times analyzed, which was confirmed by echocardiographic analyses of 8HC group. Impaired contractility indices of HC groups were observed by left ventricular catheterization, whereas ex vivo and in vitro indices of contraction under isoprenaline-stimulation were higher in HC-fed mice compared with controls. Peak levels of TNF-α, TGF-ß, ROS, TBARS, and MMP-2 occur independently of HC diet time. However, a long-lasting local reduction of the anti-inflammatory cytokine IL-10 was found, which was linearly correlated to the decline of systolic function in vivo. SIGNIFICANCE: Altogether, the results indicate that short-term consumption of HC diet negatively impacts the balance of anti-inflammatory defenses and proinflammatory/profibrotic mediators in the heart, which can contribute to HC diet-induced morphofunctional cardiac alterations.

Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation.

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein-protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Insecticidal activity of Piper aduncum oil: variation in dillapiole content and chemical and toxicological stability during storage / Atividade inseticida do óleo de Piper aduncum: variação no conteúdo de dilapiol e estabilidade química e toxicológica durante o armazenamento

The insecticidal effect of the essential oil of Piper aduncum (EOPA), and of its constituent dillapiole [1-allyl-2,3-dimethoxy-4,5- (methylenedioxy) benzene] in particular, is well documented in the literature and can be associated with its interference with the enzymatic detoxification in arthropods. However, no data exist on the range of dillapiole content associated with insecticidal activity, which is necessary to establish reliable dose-activity parameters for a formulated product. The oil composition can also change during storage after distillation, mainly due to environmental factors such as light incidence, atmospheric oxygen and temperature, which can be deleterious to oil quality. In this study, EOPA subjected to different storage conditions over four years and its rectified fractions were submitted to bioassays to evaluate their insecticidal effect by topical contact and residual contact against Spodoptera frugiperda. Our objectives were to determine the relationship between dillapiole content and the insecticidal activity of EOPA, and to evaluate its chemical and toxicological properties over time under different conditions. Our results showed that EOPA was stable with respect to the dillapiole content and the toxicological effect against S. frugiperda under different storage conditions for four years. The overall chemical composition of the EOPA did not vary significantly among storage conditions. EOPA with dillapiole content ranging between 68% and 100% showed greater insecticidal toxicity by residual and topical contact against S. frugiperda larvae.(AU)

O efeito inseticida do óleo essencial de Piper aduncum (OEPA) e, particularmente, de seu constituinte dilapiol [1-alil-2,3- dimetoxi-4,5-(metilenodioxi) benzeno], está bem documentado na literatura e pode estar associado à sua interferência na desintoxicação enzimática em artrópodes. No entanto, não existem dados sobre a amplitude de teores de dilapiol associados à atividade inseticida, o que é necessário para estabelecer parâmetros de dose-atividade confiáveis para um produto formulado. A composição do óleo também pode sofrer alterações durante seu armazenamento após a destilação, principalmente devido a fatores ambientais como incidência de luz, oxigênio atmosférico e temperatura, que podem ser deletérios à qualidade do óleo. Neste estudo, durante quatro anos, OEPA submetido a diferentes condições de armazenamento e suas frações retificadas foram submetidos a bioensaios para avaliar seu efeito inseticida por contato tópico e contato residual contra Spodoptera frugiperda. Nossos objetivos foram determinar a relação entre o teor de dilapiol e a atividade inseticida do OEPA, e avaliar suas propriedades químicas e toxicológicas ao longo do tempo sob diferentes condições. Nossos resultados mostraram que o OEPA foi estável em relação ao teor de dilapiol e o efeito toxicológico contra S. frugiperda sob diferentes condições de armazenamento durante quatro anos. A composição química do OEPA não variou significativamente entre as condições de armazenamento. OEPA com teor de dilapiol entre 68% e 100% apresentou maior toxicidade inseticida por contato residual e tópico contra larvas de S. frugiperda.(AU)

Defining dysmorphic facial features in congenital Zika syndrome.

Congenital Zika syndrome (CZS) constitutes a recently identified malformation caused by Zika virus infection during pregnancy. Limited data is available to date on the facial dysmorphic features of these patients. This study evaluated the facial dysmorphisms of children with CZS, compared with clinically healthy children, using clinical examination and standardized photographic images. Sixty-three children with CZS (9.70 ± 3.2 months-age), and 31 Controls (8.67 ± 6.2 months-age) joined the study. Seven out of 15 indices differed between groups: midfacial height (MFH)/horizontal facial reference (HFR) (p = .0003), interalar distance/HFR (p = .0027), nasal root depth/MFH (p = .0030), posterior nasal length/MFH (p = .0002), vertical position of the ear/MFH (p <.0001), ear length/MFH (p = .0005), chin height/total facial height (CH/TFH) (p <.0001). A CH/TFH of 0.229 showed 93.9% sensitivity and 80.6% specificity in diagnosing CZS. Children with CZS had broad, short faces, decreased intercanthal distance, short posterior nasal length, prominent nasal root, broad nasal wings, and high-set and long ears. Increased chin height index provided the most accurate diagnostic potential.

Penectomia em equino com parafimose / Partial penectomy in a horse with paraphimosis

Background: In horses, an increase in the volume of penis and foreskin can be caused by trauma. The resultant edema interferes with the retraction of the penis and cause paraphimosis. Surgical intervention through penectomy is indicated in cases wherein an alternative treatment is not feasible. Partial penectomy can prolong the life and reproductive function of many stallions. The present study aims to report on the methodological, functional, and economic feasibility of a successful case of the use of Williams technique for partial penectomy performed in the field in a horse with paraphimosis, preserving urinary, productive, and reproductive functions. Case: A 10-year-old horse weighing 500 kg had clinical signs of paraphimosis due to the formation of granulomatous tissue following trauma to the glans region. A surgical intervention, namely a partial penectomy was decided to be performed to prevent injury from priapism. Due to the limited resources provided by the owner and the impossibility of moving the animal to a surgical center in a veterinary hospital, the procedure was performed in the field, with prior sanitization and preparation of the environment used to perform surgery. The horse was tranquilized with intravenous xylazine hydrochloride and acepromazine, with subsequent induction of anesthesia with ready-to-use (RTU) guaifenesin bolus and maintenance of anesthesia with an intravenous association of RTU guaifenesin, xylazine hydrochloride, and ketamine. The distal third of the penis was amputated using the recommended Williams technique. Although the complications like dehiscence and emergence of granulation tissue occurred after surgery, these were controlled in the daily follow-up of the animal and post-surgical treatment. Discussion: Paraphimosis predisposed the horse to abrasions and edema of the exposed portion of the penis. However, there was no urine retention, which suggested that the urethral ostium and the urethra had no lesions. Because the granulomatous lesions were located in the distal third of the penis and the extent of penile exposure was small, the partial penectomy technique proved effective in solving the permanent exposure of the penis. The anesthetic protocol used was inexpensive, easy to execute, and effective, and no anesthetic complications occurred, proving this protocol to be efficient for the anesthetic induction of animals in the field. In addition to being reliable and widespread, the Williams technique was recommended to prevent possible urethral stenosis and the development of contact dermatitis by urine. This technique makes a rapid recovery of the animal possible, with improvement of its physiological parameters, and due to ease of being able to be done in the field, it is also inexpensive. The edema and the granulation tissue that occurred after surgery were controlled with medication. In general, post-penectomy animals are not used for reproduction. This makes the present report an important contribution, because in cases in which the lesions present a distal disposition and the penile exposure is small, stallions have a chance of maintaining reproductive function after surgery, even with a long period of evolution before surgical treatment. This was demonstrated in the present case, as the animal in this case later impregnated a mare, with the pregnancy confirmed by ultrasound examination. Partial penectomy is a resolution technique for cases of traumatic paraphimosis, in which exuberant granulation tissue is formed in the distal third of the penis, with a long period of evolution. The surgery can be done in the field, with a low surgical cost to the owner, and a good productive and reproductive prognosis for the animal.

Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII.

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca2+ dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca2+ spark rate and enhanced Ca2+ reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca2+ transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.

Neotropical carnivores: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non‐detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non‐governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peerreviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non‐detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio‐temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other largescale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data.

A New Structural Health Monitoring Strategy Based on PZT Sensors and Convolutional Neural Network.

Preliminaries convolutional neural network (CNN) applications have recently emerged in structural health monitoring (SHM) systems focusing mostly on vibration analysis. However, the SHM literature shows clearly that there is a lack of application regarding the combination of PZT-(lead zirconate titanate) based method and CNN. Likewise, applications using CNN along with the electromechanical impedance (EMI) technique applied to SHM systems are rare. To encourage this combination, an innovative SHM solution through the combination of the EMI-PZT and CNN is presented here. To accomplish this, the EMI signature is split into several parts followed by computing the Euclidean distances among them to form a RGB (red, green and blue) frame. As a result, we introduce a dataset formed from the EMI-PZT signals of 720 frames, encompassing a total of four types of structural conditions for each PZT. In a case study, the CNN-based method was experimentally evaluated using three PZTs glued onto an aluminum plate. The results reveal an effective pattern classification; yielding a 100% hit rate which outperforms other SHM approaches. Furthermore, the method needs only a small dataset for training the CNN, providing several advantages for industrial applications.

Lingual Frenulum Phenotypes in Brazilian Infants With Congenital Zika Syndrome.

OBJECTIVE: The present study aimed to evaluate lingual frenulum in children affected by congenital Zika syndrome (CZS) and to analyze the association of lingual frenulum phenotypes with other variables. DESIGN: This present work had a cross-sectional, descriptive study design. SETTING: This study was carried out in Fortaleza (Brazil). The health professionals provided tertiary level of care. Data collection occurred during a multidisciplinary task force for evaluating infants affected by CZS in December 2 to 3, 2016. PATIENTS: Fifty-four patients with CZS (1-12 months old; 32 girls and 22 boys) were recruited from a population of 70 infants. INTERVENTIONS: A multidisciplinary group comprised of speech-language pathologist/audiologists and pediatric dentists evaluated all patients through an intraoral examination and a specific tongue maneuver protocol for infants. MAIN OUTCOME MEASURES: Lingual frenulum visibility was the primary outcome measure. Before initiating the study, we hypothesized that children with CZS had an absent lingual frenulum. RESULTS: Lingual frenula were visible in 34 (63%) infants, whereas in 20 (37%) infants lingual frenula visibility required a specific maneuver to retract the tongue. Six of 20 infants presented posteriorly positioned lingual frenula that were visible after maneuver. Lingual frenula were covered by mucous tissue in 14 infants. Presence of posterior frenulum was associated with dysphagia ( P = 0.038). However, the presence of dysphagia in a multivariate model did not associate with the presence of a posterior lingual frenulum ( P = .069) or neurologic symptoms ( P = .056). CONCLUSION: Children with CZS showed predominance of a posterior lingual frenula covered by an overlapping curtain-like mucous membrane.

Avaliação da transferência de imunidade passiva e de constituintes séricos de cordeiros Santa Inês nascidos de partos simples e gemelares no semiárido paraibano / Evaluation of passive immunity transfer and serum constituents of Santa Ines lambs born of single and twin pregnancies in the semiarid region of Paraiba, Brazil

O presente trabalho teve por objetivo avaliar a influência do tipo de parto sobre a transferência de imunidade passiva e de alguns constituintes séricos de cordeiros recém-nascidos, alimentados naturalmente com colostro materno, criados no semiárido paraibano em sistema extensivo. Foram utilizados 34 cordeiros clinicamente sadios, da raça Santa Inês, os quais foram identificados e pesados imediatamente após o nascimento e separados em dois grupos experimentais com 17 animais cada. O grupo PS (nove machos e oito fêmeas) formado por animais nascidos de partos simples e o grupo PG (seis machos e onze fêmeas) formado por cordeiros nascidos de partos gemelares. A ingestão de colostro se deu de forma natural e voluntária em suas respectivas mães. Foram coletados 10 mL de sangue de cada animal, mediante punção da veia jugular, em tubos siliconizados a vácuo, 48 horas após o nascimento. Após centrifugação, as alíquotas de soro foram separadas e permaneceram congeladas a -15°C até o momento das análises. Para o estudo comparativo dos constituintes séricos, foram constituídos dois grupos experimentais distribuídos em um delineamento inteiramente casualizado, no esquema fatorial 2x2 (tipo de parto e sexo). Os dados obtidos foram submetidos à análise de variância, cujas médias foram comparadas pelo teste de Tukey a 5%. Foram determinadas as atividades séricas das enzimas aspartato aminotransferase (AST) e gamaglutamiltransferase (GGT) e as concentrações séricas de proteína total, albumina, ureia, creatinina, cálcio, fósforo e magnésio, utilizando-se conjuntos de reagentes comerciais e as leituras das amostras em espectrofotômetro automático. As atividades séricas de AST, GGT e as concentrações séricas de proteína total, albumina e globulinas dos cordeiros dos grupos PS e PG não foram influenciadas pelo tipo de gestação e sexo...(AU)

This study is concerned with an evaluation of the influence of mode of birth on the transfer of passive immunity and some serum constituents to newborn lambs, naturally fed with colostrum, breed in the semiarid region of the State of Paraiba (Brazil) on an extensive system. Thirty-four clinically healthy Santa Ines lambs were employed, identified and weighted immediately after birth, and divided into two experimental groups of seventeen animals each. The PS group (nine males and eight females) included lambs born of single pregnancies and the PG group (six males and eleven females) comprised of lambs born of twin pregnancies. The colostrum intake occurred naturally and voluntarily at their mothers. Forty-eight hours after birth, 10 mL of blood were collected in siliconized tubes from each animal by puncture of the jugular vein, and maintained under vacuum. After centrifugation, aliquots of sera were separated and kept frozen at -15°C until analyzed. For the comparative study of serum constituents, two experimental groups were formed, distributed in a completely randomized lineation, 2x2 factorial (type of birth and sex). The data were subjected to analysis of variance, whose means were compared by Tukey test at 5%. The serum activities of AST and GGT, and the total protein serum, albumin, urea, creatinine, calcium, phosphorus and magnesium concentrations were determined by using sets of commercial reagents; the samples were read by an automatic spectrophotometer. The serum activities of AST, GGT and serum concentrations of total protein, albumin and globulins of the PS and PG lambs groups were not influenced by the type of pregnancy and sex. From the serum concentration of total protein, FTIP was found in the lambs of PG group, using the value of 5.0g/dL as the cutoff point. With the exception of calcium, serum concentrations of urea, creatinine, phosphorus and magnesium showed the same pattern...(AU)

Avaliação da transferência de imunidade passiva e de constituintes séricos de cordeiros Santa Inês nascidos de partos simples e gemelares no semiárido paraibano / Evaluation of passive immunity transfer and serum constituents of Santa Ines lambs born of single and twin pregnancies in the semiarid region of Paraiba, Brazil

O presente trabalho teve por objetivo avaliar a influência do tipo de parto sobre a transferência de imunidade passiva e de alguns constituintes séricos de cordeiros recém-nascidos, alimentados naturalmente com colostro materno, criados no semiárido paraibano em sistema extensivo. Foram utilizados 34 cordeiros clinicamente sadios, da raça Santa Inês, os quais foram identificados e pesados imediatamente após o nascimento e separados em dois grupos experimentais com 17 animais cada. O grupo PS (nove machos e oito fêmeas) formado por animais nascidos de partos simples e o grupo PG (seis machos e onze fêmeas) formado por cordeiros nascidos de partos gemelares. A ingestão de colostro se deu de forma natural e voluntária em suas respectivas mães. Foram coletados 10 mL de sangue de cada animal, mediante punção da veia jugular, em tubos siliconizados a vácuo, 48 horas após o nascimento. Após centrifugação, as alíquotas de soro foram separadas e permaneceram congeladas a -15°C até o momento das análises. Para o estudo comparativo dos constituintes séricos, foram constituídos dois grupos experimentais distribuídos em um delineamento inteiramente casualizado, no esquema fatorial 2x2 (tipo de parto e sexo). Os dados obtidos foram submetidos à análise de variância, cujas médias foram comparadas pelo teste de Tukey a 5%. Foram determinadas as atividades séricas das enzimas aspartato aminotransferase (AST) e gamaglutamiltransferase (GGT) e as concentrações séricas de proteína total, albumina, ureia, creatinina, cálcio, fósforo e magnésio, utilizando-se conjuntos de reagentes comerciais e as leituras das amostras em espectrofotômetro automático. As atividades séricas de AST, GGT e as concentrações séricas de proteína total, albumina e globulinas dos cordeiros dos grupos PS e PG não foram influenciadas pelo tipo de gestação e sexo. A partir da concentração sérica de proteína total, verificou-se falha de transferência de imunidade passiva (FTIP) nos cordeiros do grupo PG, utilizando-se o valor 5,0g/dL como ponto de corte. Com exceção do cálcio, as concentrações séricas da ureia, creatinina, fósforo e magnésio apresentaram o mesmo padrão de comportamento. Embora esses constituintes não tenham apresentado diferença significativa entre os grupos estudados e o sexo, pôde-se observar valores mais elevados nos animais nascidos de partos simples, sugerindo que a ausência de concorrência pela ingestão voluntária de colostro materno pode ter sido o fator determinante. Pode-se concluir que cordeiros Santa Inês nascidos de partos gemelares e criados extensivamente no semiárido paraibano apresentam falha na transferência de imunidade passiva e alterações/diminuições marcantes nos teores séricos de alguns constituintes bioquímicos, suscitando a necessidade de interferência humana nestes casos.(AU)

This study is concerned with an evaluation of the influence of mode of birth on the transfer of passive immunity and some serum constituents to newborn lambs, naturally fed with colostrum, breed in the semiarid region of the State of Paraiba (Brazil) on an extensive system. Thirty-four clinically healthy Santa Ines lambs were employed, identified and weighted immediately after birth, and divided into two experimental groups of seventeen animals each. The PS group (nine males and eight females) included lambs born of single pregnancies and the PG group (six males and eleven females) comprised of lambs born of twin pregnancies. The colostrum intake occurred naturally and voluntarily at their mothers. Forty-eight hours after birth, 10 mL of blood were collected in siliconized tubes from each animal by puncture of the jugular vein, and maintained under vacuum. After centrifugation, aliquots of sera were separated and kept frozen at -15°C until analyzed. For the comparative study of serum constituents, two experimental groups were formed, distributed in a completely randomized lineation, 2x2 factorial (type of birth and sex). The data were subjected to analysis of variance, whose means were compared by Tukey test at 5%. The serum activities of AST and GGT, and the total protein serum, albumin, urea, creatinine, calcium, phosphorus and magnesium concentrations were determined by using sets of commercial reagents; the samples were read by an automatic spectrophotometer. The serum activities of AST, GGT and serum concentrations of total protein, albumin and globulins of the PS and PG lambs groups were not influenced by the type of pregnancy and sex. From the serum concentration of total protein, FTIP was found in the lambs of PG group, using the value of 5.0g/dL as the cutoff point. With the exception of calcium, serum concentrations of urea, creatinine, phosphorus and magnesium showed the same pattern. Although these constituents did not showed significant differences between groups and sex, higher values were observed in animals born of single pregnancies, suggesting that the absence of competition for the voluntary ingestion of colostrum may have been the determining factor. It can be concluded that lambs born twin deliveries and breed extensively in the semiarid region of the State of Paraiba failed to transfer passive immunity and showed significant reduction in serum levels of some biochemical constituents, indicating the need for human interference in these cases.(AU)

Avaliação da transferência de imunidade passiva e de constituintes séricos de cordeiros Santa Inês nascidos de partos simples e gemelares no semiárido paraibano

ABSTRACT: This study is concerned with an evaluation of the influence of mode of birth on the transfer of passive immunity and some serum constituents to newborn lambs, naturally fed with colostrum, breed in the semiarid region of the State of Paraiba (Brazil) on an extensive system. Thirty-four clinically healthy Santa Ines lambs were employed, identified and weighted immediately after birth, and divided into two experimental groups of seventeen animals each. The PS group (nine males and eight females) included lambs born of single pregnancies and the PG group (six males and eleven females) comprised of lambs born of twin pregnancies. The colostrum intake occurred naturally and voluntarily at their mothers. Forty-eight hours after birth, 10 mL of blood were collected in siliconized tubes from each animal by puncture of the jugular vein, and maintained under vacuum. After centrifugation, aliquots of sera were separated and kept frozen at -15°C until analyzed. For the comparative study of serum constituents, two experimental groups were formed, distributed in a completely randomized lineation, 2x2 factorial (type of birth and sex). The data were subjected to analysis of variance, whose means were compared by Tukey test at 5%. The serum activities of AST and GGT, and the total protein serum, albumin, urea, creatinine, calcium, phosphorus and magnesium concentrations were determined by using sets of commercial reagents; the samples were read by an automatic spectrophotometer. The serum activities of AST, GGT and serum concentrations of total protein, albumin and globulins of the PS and PG lambs groups were not influenced by the type of pregnancy and sex. From the serum concentration of total protein, FTIP was found in the lambs of PG group, using the value of 5.0g/dL as the cutoff point. With the exception of calcium, serum concentrations of urea, creatinine, phosphorus and magnesium showed the same pattern. Although these constituents did not showed significant differences between groups and sex, higher values were observed in animals born of single pregnancies, suggesting that the absence of competition for the voluntary ingestion of colostrum may have been the determining factor. It can be concluded that lambs born twin deliveries and breed extensively in the semiarid region of the State of Paraiba failed to transfer passive immunity and showed significant reduction in serum levels of some biochemical constituents, indicating the need for human interference in these cases.

RESUMO: O presente trabalho teve por objetivo avaliar a influência do tipo de parto sobre a transferência de imunidade passiva e de alguns constituintes séricos de cordeiros recém-nascidos, alimentados naturalmente com colostro materno, criados no semiárido paraibano em sistema extensivo. Foram utilizados 34 cordeiros clinicamente sadios, da raça Santa Inês, os quais foram identificados e pesados imediatamente após o nascimento e separados em dois grupos experimentais com 17 animais cada. O grupo PS (nove machos e oito fêmeas) formado por animais nascidos de partos simples e o grupo PG (seis machos e onze fêmeas) formado por cordeiros nascidos de partos gemelares. A ingestão de colostro se deu de forma natural e voluntária em suas respectivas mães. Foram coletados 10 mL de sangue de cada animal, mediante punção da veia jugular, em tubos siliconizados a vácuo, 48 horas após o nascimento. Após centrifugação, as alíquotas de soro foram separadas e permaneceram congeladas a -15°C até o momento das análises. Para o estudo comparativo dos constituintes séricos, foram constituídos dois grupos experimentais distribuídos em um delineamento inteiramente casualizado, no esquema fatorial 2x2 (tipo de parto e sexo). Os dados obtidos foram submetidos à análise de variância, cujas médias foram comparadas pelo teste de Tukey a 5%. Foram determinadas as atividades séricas das enzimas aspartato aminotransferase (AST) e gamaglutamiltransferase (GGT) e as concentrações séricas de proteína total, albumina, ureia, creatinina, cálcio, fósforo e magnésio, utilizando-se conjuntos de reagentes comerciais e as leituras das amostras em espectrofotômetro automático. As atividades séricas de AST, GGT e as concentrações séricas de proteína total, albumina e globulinas dos cordeiros dos grupos PS e PG não foram influenciadas pelo tipo de gestação e sexo. A partir da concentração sérica de proteína total, verificou-se falha de transferência de imunidade passiva (FTIP) nos cordeiros do grupo PG, utilizando-se o valor 5,0g/dL como ponto de corte. Com exceção do cálcio, as concentrações séricas da ureia, creatinina, fósforo e magnésio apresentaram o mesmo padrão de comportamento. Embora esses constituintes não tenham apresentado diferença significativa entre os grupos estudados e o sexo, pôde-se observar valores mais elevados nos animais nascidos de partos simples, sugerindo que a ausência de concorrência pela ingestão voluntária de colostro materno pode ter sido o fator determinante. Pode-se concluir que cordeiros Santa Inês nascidos de partos gemelares e criados extensivamente no semiárido paraibano apresentam falha na transferência de imunidade passiva e alterações/diminuições marcantes nos teores séricos de alguns constituintes bioquímicos, suscitando a necessidade de interferência humana nestes casos.

Promethazine improves antibiotic efficacy and disrupts biofilms of Burkholderia pseudomallei.

Efflux pumps are important defense mechanisms against antimicrobial drugs and maintenance of Burkholderia pseudomallei biofilms. This study evaluated the effect of the efflux pump inhibitor promethazine on the structure and antimicrobial susceptibility of B. pseudomallei biofilms. Susceptibility of planktonic cells and biofilms to promethazine alone and combined with antimicrobials was assessed by the broth microdilution test and biofilm metabolic activity was determined with resazurin. The effect of promethazine on 48 h-grown biofilms was also evaluated through confocal and electronic microscopy. The minimum inhibitory concentration (MIC) of promethazine was 780 mg l-1, while the minimum biofilm elimination concentration (MBEC) was 780-3,120 mg l-1. Promethazine reduced the MIC values for erythromycin, trimethoprim/sulfamethoxazole, gentamicin and ciprofloxacin and reduced the MBEC values for all tested drugs (p<0.05). Microscopic analyses demonstrated that promethazine altered the biofilm structure of B. pseudomallei, even at subinhibitory concentrations, possibly facilitating antibiotic penetration. Promethazine improves antibiotics efficacy against B. pseudomallei biofilms, by disrupting biofilm structure.

Combining the essential oil of Piper aduncum L. with commercial insecticides / Combinação do óleo essencial de Piper aduncum L. com inseticidas comerciais

The use of synergists is important in minimizing the amount of chemical insecticide required for insect control. Their use can contribute to reducing environmental contamination and preserving beneficial insects. To further investigate a promising alternative to the synergist piperonyl butoxide (PBO), we compared the synergistic effects of PBO and Piper aduncum L. essential oil (PAEO) when combined with several insecticides (cypermethrin, zeta-cypermethrin, permethrin, and esfenvalerate) on the larvae of Spodoptera frugiperda (J. E. Smith, 1797). Initially, we determined the lethal doses and concentrations (LD50 and LC50) for S. frugiperda larvae subjected to separate treatments with PAEO and with each commercial insecticide. Subsequently, in order to evaluate the synergistic effect, combinations of sublethal doses or sublethal concentrations of the essential oil (½ and » of the LD50 or LC50, respectively) were prepared with sublethal doses or sublethal concentrations of the insecticides (below the LD40 or LC40). To confirm the evidence of the synergistic efficacy of the PAEO, the same reduced concentrations and doses of the insecticides that were previously used in combinations with the oil were also combined with PBO at a ratio of 10:1 (PBO:Insecticide). Through the relationship between the CL50 and DL50 of the insecticides taken separately and in their synergistic combinations with the PAEO and PBO, synergism factors (SF) were calculated for the various combinations. With residual contact, there was a significant enhancement of the commercial insecticides formulated with cypermethrin (SF = 73.03), zeta-cypermethrin (SF = 16.51), and permethrin (SF = 8.46-17.22) when combined with the PAEO; by contrast, with topical application there was a significant enhancement only for zeta-cypermethrin (SF = 0.40-4.26), permethrin (SF = 2.10-4.79), and esfenvalerate (SF = 3.80) when combined with the essential oil.[...]

A importância da utilização de sinergistas está relacionada à minimização da quantidade de inseticida químico necessária para o controle de insetos, podendo contribuir com a diminuição da contaminação ambiental e preservação de insetos benéficos. Na busca de uma alternativa ao butóxido de piperonila (PBO), o estudo comparou os efeitos do PBO e do óleo essencial de Piper aduncum L. combinados com os inseticidas cipermetrina, permetrina e esfenvalerato, quanto ao efeito sinérgico e homogeneidade de resposta de larvas de Spodoptera frugiperda (J. E. Smith, 1797). Inicialmente foram determinadas as doses e concentrações letais (DL50 e CL50) para larvas de S. frugiperda submetidas ao tratamento com o OEPA assim como para cada inseticida comercial considerados de forma isolada. Posteriormente, para avaliação do efeito sinérgico, foram realizadas combinações das doses e concentrações sub-letais com o óleo essencial (metade e um quarto da DL50 ou CL50, respectivamente) com as doses e concentrações sub-letais dos inseticidas comerciais (abaixo das DL40 ou CL40, respectivamente). Para complementar a comprovação da eficácia sinérgica do OEPA, foram utilizados como tratamentos adicionais as mesmas sub-concentrações e sub-doses dos inseticidas utilizadas anteriormente nas combinações com o óleo, passando a ser combinadas com o PBO na proporção de 10:1 (PBO: Inseticida). Por meio da relação das CL50 e DL50 dos inseticidas tomados isoladamente e de suas respectivas combinações sinérgicas com o OEPA e o PBO, foram obtidos os fatores de sinergismo (FS) para comparação entre si. Por contato residual foi evidenciada significativa potencialização dos inseticidas comerciais formulados com cipermetrina (FS= 73,03), zeta-cipermetrina (FS= 16,51) e permetrina (FS= 8,46-17,22), quando combinados com o OEPA.[...]

Combining the essential oil of Piper aduncum L. with commercial insecticides / Combinação do óleo essencial de Piper aduncum L. com inseticidas comerciais

The use of synergists is important in minimizing the amount of chemical insecticide required for insect control. Their use can contribute to reducing environmental contamination and preserving beneficial insects. To further investigate a promising alternative to the synergist piperonyl butoxide (PBO), we compared the synergistic effects of PBO and Piper aduncum L. essential oil (PAEO) when combined with several insecticides (cypermethrin, zeta-cypermethrin, permethrin, and esfenvalerate) on the larvae of Spodoptera frugiperda (J. E. Smith, 1797). Initially, we determined the lethal doses and concentrations (LD50 and LC50) for S. frugiperda larvae subjected to separate treatments with PAEO and with each commercial insecticide. Subsequently, in order to evaluate the synergistic effect, combinations of sublethal doses or sublethal concentrations of the essential oil (½ and » of the LD50 or LC50, respectively) were prepared with sublethal doses or sublethal concentrations of the insecticides (below the LD40 or LC40). To confirm the evidence of the synergistic efficacy of the PAEO, the same reduced concentrations and doses of the insecticides that were previously used in combinations with the oil were also combined with PBO at a ratio of 10:1 (PBO:Insecticide). Through the relationship between the CL50 and DL50 of the insecticides taken separately and in their synergistic combinations with the PAEO and PBO, synergism factors (SF) were calculated for the various combinations. With residual contact, there was a significant enhancement of the commercial insecticides formulated with cypermethrin (SF = 73.03), zeta-cypermethrin (SF = 16.51), and permethrin (SF = 8.46-17.22) when combined with the PAEO; by contrast, with topical application there was a significant enhancement only for zeta-cypermethrin (SF = 0.40-4.26), permethrin (SF = 2.10-4.79), and esfenvalerate (SF = 3.80) when combined with the essential oil.[...](AU)

A importância da utilização de sinergistas está relacionada à minimização da quantidade de inseticida químico necessária para o controle de insetos, podendo contribuir com a diminuição da contaminação ambiental e preservação de insetos benéficos. Na busca de uma alternativa ao butóxido de piperonila (PBO), o estudo comparou os efeitos do PBO e do óleo essencial de Piper aduncum L. combinados com os inseticidas cipermetrina, permetrina e esfenvalerato, quanto ao efeito sinérgico e homogeneidade de resposta de larvas de Spodoptera frugiperda (J. E. Smith, 1797). Inicialmente foram determinadas as doses e concentrações letais (DL50 e CL50) para larvas de S. frugiperda submetidas ao tratamento com o OEPA assim como para cada inseticida comercial considerados de forma isolada. Posteriormente, para avaliação do efeito sinérgico, foram realizadas combinações das doses e concentrações sub-letais com o óleo essencial (metade e um quarto da DL50 ou CL50, respectivamente) com as doses e concentrações sub-letais dos inseticidas comerciais (abaixo das DL40 ou CL40, respectivamente). Para complementar a comprovação da eficácia sinérgica do OEPA, foram utilizados como tratamentos adicionais as mesmas sub-concentrações e sub-doses dos inseticidas utilizadas anteriormente nas combinações com o óleo, passando a ser combinadas com o PBO na proporção de 10:1 (PBO: Inseticida). Por meio da relação das CL50 e DL50 dos inseticidas tomados isoladamente e de suas respectivas combinações sinérgicas com o OEPA e o PBO, foram obtidos os fatores de sinergismo (FS) para comparação entre si. Por contato residual foi evidenciada significativa potencialização dos inseticidas comerciais formulados com cipermetrina (FS= 73,03), zeta-cipermetrina (FS= 16,51) e permetrina (FS= 8,46-17,22), quando combinados com o OEPA.[...](AU)

Terpinen-4-ol, tyrosol, and ß-lapachone as potential antifungals against dimorphic fungi

Abstract This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and β-lapachone against strains of Coccidioides posadasii in filamentous phase (n = 22) and Histoplasma capsulatum in both filamentous (n = 40) and yeast phases (n = 13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 µg/mL, 20-2860 µg/mL, and 40-1420 µg/mL, respectively for terpinen-4-ol; 250-4000 µg/mL, 30-2000 µg/mL, and 10-1000 µg/mL, respectively, for tyrosol; and 0.48-7.8 µg/mL, 0.25-16 µg/mL, and 0.125-4 µg/mL, respectively for β-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.

Terpinen-4-ol, tyrosol, and -lapachone as potential antifungals against dimorphic fungi

This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and -lapachone against strains of Coccidioides posadasii in filamentous phase (n = 22) and Histoplasma capsulatum in both filamentous (n = 40) and yeast phases (n = 13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 µg/mL, 20-2860 µg/mL, and 40-1420 µg/mL, respectively for terpinen-4-ol; 250-4000 µg/mL, 30-2000 µg/mL, and 10-1000 µg/mL, respectively, for tyrosol; and 0.48-7.8 µg/mL, 0.25-16 µg/mL, and 0.125-4 µg/mL, respectively for -lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.(AU)