Neem Essential Oil as an Antifungal Agent against Phyllosticta citricarpa.

The fungus Phyllosticta citricarpa is a quarantine phytopathogen responsible for causing citrus black spot (CBS) disease. To export fruits to CBS-free countries, they must undergo a sanitation process to ensure disease control. In this study, neem essential oil (NEO) was tested against P. citricarpa for the first time as an alternative sanitizer. In vitro experiments were conducted to determine the inhibition concentration of NEO for P. citricarpa, and the mode of action of the essential oil was evaluated. In vivo assays were performed to simulate the sanitization process used in packinghouses. NEO was characterized by GC-MS/MS. The results revealed that NEO at 100 µL·mL-1 exhibited a similar inhibitory effect as copper oxychloride, suppressing 89.68 ± 1.14% of fungal mycelium growth. Fluorescence microscopy experiments demonstrated that NEO functions by disrupting the cytoplasmic membrane of fungal hyphae, leading to their death within 30 minutes of contact with NEO. GC-MS/MS characterization revealed a high presence of phenolic compounds, which serve as the primary antifungal agents responsible for the action against fungal hyphae. In vivo assays showed that NEO at 100 µL·mL-1 also reduced microorganisms (CFU mL-1) by 93.00 ± 3.88% compared to the negative control. Overall, the results demonstrate that NEO can effectively serve as an alternative sanitizer against P. citricarpa in citrus packinghouses. Our findings allow future studies to explore the use of NEO for sanitizing other fruits and combating different phytopathogens to broaden its potential application in fruit sanitation for export.

Long-term recruitment of peripheral immune cells to brain scars after a neonatal insult.

Although brain scars in adults have been extensively studied, there is less data available regarding scar formation during the neonatal period, and the involvement of peripheral immune cells in this process remains unexplored in neonates. Using a murine model of neonatal hypoxic-ischemic encephalopathy (HIE) and confocal microscopy, we characterized the scarring process and examined the recruitment of peripheral immune cells to cortical and hippocampal scars for up to 1 year post-insult. Regional differences in scar formation were observed, including the presence of reticular fibrotic networks in the cortex and perivascular fibrosis in the hippocampus. We identified chemokines with chronically elevated levels in both regions and demonstrated, through a parabiosis-based strategy, the recruitment of lymphocytes, neutrophils, and monocyte-derived macrophages to the scars several weeks after the neonatal insult. After 1 year, however, neutrophils and lymphocytes were absent from the scars. Our data indicate that peripheral immune cells are transient components of HIE-induced brain scars, opening up new possibilities for late therapeutic interventions.

Drug-Related Adverse Reactions in Pediatric Inflammatory Bowel Disease.

The therapeutic approach to inflammatory bowel disease (IBD) is complex, often involving multiple pharmacologic classes. We aimed to evaluate the prevalence of drug-related adverse reactions (ARs) associated with therapies used in pediatric IBD. We conducted a retrospective study of pediatric patients with IBD followed in a tertiary hospital from 2010 to 2022. Ninety-nine patients were included (62.6% were male), with a median age at diagnosis of 13 years (interquartile range [IQR] 11-15 years). The majority had Crohn's disease (69.7%), followed by ulcerative colitis (21.2%) and unclassified IBD (9.1%). The most prescribed therapies were: immunomodulators (n = 75, 75.8%), exclusive enteral nutrition (n = 61, 61.6%), and biologics (n = 58, 58.6%). During a median follow-up time of 31 months (IQR 11-51 months), the incidence of ARs was 16.2% (16 ARs occurred in 14 patients). The main drug involved was azathioprine (12/16) and the most frequent AR was hepatitis (5/16). Drug discontinuation was necessary in all but 1 case. Of the ARs recorded, 75% were mild to moderate and 81.3% did not require specific treatment; all patients had clinical and/or analytical normalization. There was a positive association between the cumulative number of prescribed drugs and the occurrence of ARs (P = .044). The incidence of ARs was similar to the rates reported in the few existing previous studies. The majority of ARs were mild, but implied the discontinuation of therapy or dose reduction, with a possible impact on disease control.

Reduction of seizures and inflammatory markers by betamethasone in a kindling seizure model.

Epilepsy is a chronic disease characterized by an ongoing predisposition to seizures. Although inflammation has emerged as a crucial factor in the etiology of epilepsy, no approaches to anti-inflammatory treatment have been clinically proven to date. Betamethasone (a corticosteroid drug used in the clinic for its anti-inflammatory and immunosuppressive effects) has never been evaluated in attenuating the intensity of seizures in a kindling animal model of seizures. Using a kindling model in male wistar rats, this study evaluated the effect of betamethasone on the severity of seizures and levels of pro-inflammatory interleukins. Seizures were induced by pentylenetetrazole (30 mg/kg) on alternate days for 15 days. The animals were divided into four groups: a control group treated with saline, another control group treated with diazepam (2 mg/kg), and two groups treated with betamethasone (0.125 and 0.250 mg/kg, respectively). Open field test was conducted. Betamethasone treatments were effective in reducing the intensity of epileptic seizures. There were lower levels of Tumor Necrosis Factor-α and interleukin-1ß in the cortex, compared to the saline group, on the other hand, levels in the hippocampus remained similar to the control groups. There was no change in the levels of interleukin-6 in the evaluated structures. Serum inflammatory mediators remained similar. Lower quantities of inflammatory mediators in the central nervous system may have been the key to the reduced severity of seizures on the Racine scale.

Transtorno depressivo em mulheres no período pós-parto: análise segundo a raça/cor autorreferida / Trastorno depresivo en mujeres en el período posparto: análisis según raza/color autodeclarado / Depressive disorder among postpartum women: an analysis according to self-reported race/color

Resumo Objetivo Identificar a raça/cor autorreferida por mulheres com 60 dias de pós-parto; identificar a prevalência do indicativo de transtorno depressivo nessas mulheres e verificar a associação entre o indicativo de transtorno depressivo e o quesito raça/cor autorreferida. Métodos Estudo transversal desenvolvido em um município do interior paulista. Foram utilizados, para a coleta de dados, um instrumento com dados sociodemográficos e a Escala de Depressão Pós-Natal de Edimburgo. Os dados foram analisados utilizando-se o Statistical Package for Social Sciences, SPSS, versão 17.0. Resultados Participaram deste estudo 186 mulheres, 60,8% referiram ser da cor parda, 24,2% apresentaram indicativo de transtorno depressivo e, entre estas, 81,7% eram da raça negra. O indicativo de transtorno depressivo associou-se às variáveis: número de filhos (p=0,006), gestação planejada (p=0,04) e tipo de parto (p< 0,001). Conclusão Os resultados deste estudo contribuem para maior visibilidade da temática da saúde mental das mulheres, especificamente das mulheres negras, pois, mesmo que não tenha sido identificada associação significativa dentre aquelas que apresentaram indicativo de transtorno depressivo, a maioria era da raça negra.

Resumen Objetivo Identificar la raza/color autodeclarado por mujeres con 60 días de posparto, identificar la prevalencia de indicios de trastorno depresivo en esas mujeres y verificar la relación entre los indicios de trastorno depresivo y el ítem raza/color autodeclarado. Métodos Estudio transversal realizado en un municipio del interior paulista. Para la recopilación de datos, se utilizó un instrumento con datos sociodemográficos y la Escala de Depresión Posnatal de Edimburgo. Para analizar los datos se utilizó el Statistical Package for Social Sciences, SPSS, versión 17.0. Resultados Participaron en el estudio 186 mujeres, el 60,8 % declararon ser de color pardo, el 24,2 % presentó indicios de trastorno depresivo y, entre ellas, el 81,7 % era de raza negra. Los indicios de trastorno depresivo se relacionaron a las variables: número de hijos (p=0,006), embarazo planeado (p=0,04) y tipo de parto (p< 0,001). Conclusión Los resultados de este estudio contribuyen para una mayor visibilidad del tema de salud mental de las mujeres, específicamente de mujeres negras, ya que, aunque no se haya identificado una relación significativa entre las que presentaron indicios de trastorno depresivo, la mayoría era de raza negra.

Abstract Objective To identify the race/color self-reported by women 60 days postpartum; to identify the prevalence of signs of depressive disorder among these women and to verify the association between signs of depressive disorder and the self-reported race/color. Methods Cross-sectional study carried out in a noncapital city in the state of São Paulo. An instrument with sociodemographic data and the Edinburgh Postnatal Depression Scale were used for data collection. Data was analyzed using the Statistical Package for Social Sciences, SPSS, version 17.0. Results A total of 186 women participated in this study, 60.8% reported being brown, 24.2% had signs of depressive disorder and, among these, 81.7% were black. Signs of depressive disorder were associated with the variables: number of children (p=0.006), planned pregnancy (p=0.04) and type of delivery (p< 0.001). Conclusion The results of this study contribute to greater visibility of the issue of women's mental health, specifically of black women, because even though no significant association was identified among those who showed signs of depressive disorder, most were black.

Aerobic exercise, alone or combined with an anti-inflammatory drug, reduces the severity of epileptic seizures and levels of central pro-inflammatory cytokines in an animal model of epileptic seizures.

Epilepsy is a chronic neurological disorder and there is increasing evidence about the role of inflammation in epileptogenesis. These findings have spurred the search for new immunomodulatory approaches that can improve prognosis. Using an animal model of chemically-induced epileptic seizures, we tested exercise alone as non-pharmacological therapy, and exercise combined with an anti-inflammatory drug. Five groups were used: sedentary, diazepam, aerobic exercise alone, aerobic exercise combined with an anti-inflammatory drug, and naive control. Our goal was to compare the severity of the epileptic seizures between groups as well as seizure latency in a pentylenetetrazole-induced paradigm. Cytokine levels (IL-1ß, TNF-α, and IL-10) were measured. Both exercise groups showed a reduction in seizure severity and lower levels of pro-inflammatory cytokines in the cortex, while the levels of cytokines in the hippocampus remained unaffected.

Peripheral artery disease: a comparison of urgent open and endovascular revascularizations on the public health system in Brazil, from 2010 to 2020.

Background: Peripheral artery disease (PAD) has high prevalence and is associated with high risk of cardiovascular events. Surgical or endovascular intervention is necessary in chronic limb-threatening ischemia. Objectives: To evaluate the distribution of open and endovascular revascularizations in different regions of Brazil, analyzing the health system costs and mortality related to these procedures. Methods: A descriptive, cross-sectional, observational, epidemiological study was carried out to evaluate open and endovascular surgeries performed on the SUS public healthcare system in Brazil, from 2010 to 2020. Data were collected from the SUS Department of Informatics (Datasus). Results: Over the period analyzed, 83,218 admissions for open and endovascular surgeries were registered, with a total cost of R$ 333,989,523.17. There were more hospital admissions for percutaneous procedures (56,132) than for conventional surgery (27,086). Most of the procedures (83%) were performed in the country's Southeast and South regions, while the North region had the lowest number of procedures. Over the period evaluated, there was a decreasing trend for open procedures and an increasing trend for endovascular procedures. The average hospital stay was shorter for endovascular procedures (5.3 days) than for open surgery (10.2 days). The analysis of mortality related to these procedures revealed a higher rate of in-hospital mortality associated with open revascularization than with endovascular (5.24% vs. 1.56%). Conclusions: Endovascular techniques constituted the primary approach for revascularization treatment in critical limb-threatening ischemia, with a lower in-hospital mortality rate and shorter hospital stay when compared to open surgeries.

Doença arterial obstrutiva periférica: um estudo comparativo entre revascularizações abertas e endovasculares realizadas em caráter de urgência no sistema público de saúde do Brasil entre 2010 e 2020 / Peripheral artery disease: a comparison of urgent open and endovascular revascularizations on the public health system in Brazil, from 2010 to 2020

RESUMO Contexto A doença arterial obstrutiva periférica apresenta alta prevalência, sendo associada a elevado risco de eventos cardiovasculares. A intervenção cirúrgica ou endovascular faz-se necessária na isquemia crítica do membro. Objetivos Avaliar a distribuição de realização de revascularizações abertas e endovasculares nas diferentes regiões do Brasil, analisando os custos para o sistema de saúde e a mortalidade relacionada a esses procedimentos. Métodos Foi realizado um estudo epidemiológico observacional transversal descritivo para avaliar as cirurgias abertas e endovasculares realizadas no sistema público de saúde do Brasil entre 2010 e 2020. Os dados foram coletados através do Departamento de Informática do SUS (Datasus). Resultados No período analisado, foram registradas 83.218 internações para realização de cirurgias abertas e endovasculares, com um custo total de R$ 333.989.523,17. Houve predominância das internações para os procedimentos percutâneos (56.132) em relação aos cirúrgicos convencionais (27.086). As Regiões Sudeste e Sul concentraram a maior parte do total de procedimentos realizados no país (83%), enquanto a Região Norte foi a que apresentou a menor taxa de internação. Observou-se uma tendência decrescente para os procedimentos abertos, e uma tendência crescente para os endovasculares. A média de permanência hospitalar foi menor nos procedimentos endovasculares (5,3 dias) em relação aos abertos (10,2 dias). Além disso, notou-se uma maior taxa de mortalidade hospitalar relacionada à revascularização aberta em relação à endovascular (5,24% versus 1,56%). Conclusões As técnicas endovasculares consistiram em uma abordagem dominante no tratamento cirúrgico da isquemia crítica, apresentando menor taxa de mortalidade hospitalar e menor tempo de internação quando comparada às cirurgias abertas.

ABSTRACT Background Peripheral artery disease (PAD) has high prevalence and is associated with high risk of cardiovascular events. Surgical or endovascular intervention is necessary in chronic limb-threatening ischemia. Objectives To evaluate the distribution of open and endovascular revascularizations in different regions of Brazil, analyzing the health system costs and mortality related to these procedures. Methods A descriptive, cross-sectional, observational, epidemiological study was carried out to evaluate open and endovascular surgeries performed on the SUS public healthcare system in Brazil, from 2010 to 2020. Data were collected from the SUS Department of Informatics (Datasus). Results Over the period analyzed, 83,218 admissions for open and endovascular surgeries were registered, with a total cost of R$ 333,989,523.17. There were more hospital admissions for percutaneous procedures (56,132) than for conventional surgery (27,086). Most of the procedures (83%) were performed in the country's Southeast and South regions, while the North region had the lowest number of procedures. Over the period evaluated, there was a decreasing trend for open procedures and an increasing trend for endovascular procedures. The average hospital stay was shorter for endovascular procedures (5.3 days) than for open surgery (10.2 days). The analysis of mortality related to these procedures revealed a higher rate of in-hospital mortality associated with open revascularization than with endovascular (5.24% vs. 1.56%). Conclusions Endovascular techniques constituted the primary approach for revascularization treatment in critical limb-threatening ischemia, with a lower in-hospital mortality rate and shorter hospital stay when compared to open surgeries.

Protective effects of L-carnitine on behavioral alterations and neuroinflammation in striatum of glutaryl-COA dehydrogenase deficient mice.

Glutaric acidemia type 1 (GA1) is caused by glutaryl-CoA dehydrogenase deficiency that leads to a blockage in the metabolic route of the amino acids lysine and tryptophan and subsequent accumulation of glutaric acid (GA), 3-hydroxyglutaric acids and glutarylcarnitine (C5DC). Patients predominantly manifest neurological symptoms, associated with acute striatal degeneration, as well as progressive cortical and striatum injury whose pathogenesis is not yet fully established. Current treatment includes protein/lysine restriction and l-carnitine supplementation of (L-car). The aim of this work was to evaluate behavior parameters and pro-inflammatory factors (cytokines IL-1ß, TNF-α and cathepsin-D levels), as well as the anti-inflammatory cytokine IL10 in striatum of knockout mice (Gcdh-/-) and wild type (WT) mice submitted to a normal or a high Lys diet. The potential protective effects of L-car treatment on these parameters were also evaluated. Gcdh-/- mice showed behavioral changes, including lower motor activity (decreased number of crossings) and exploratory activity (reduced number of rearings). Also, Gcdh-/- mice had significantly higher concentrations of glutarylcarnitine (C5DC) in blood and cathepsin-D (CATD), interleukin IL-1ß and tumor factor necrosis alpha (TNF-α) in striatum than WT mice. Noteworthy, L-car treatment prevented most behavioral alterations, normalized CATD levels and attenuated IL-1ß levels in striatum of Gcdh-/- mice. Finally, IL-1ß was positively correlated with CATD and C5DC levels and L-car was negatively correlated with CATD. Our results demonstrate behavioral changes and a pro-inflammatory status in striatum of the animal model of GA1 and, most importantly, L-car showed important protective effects on these alterations.

A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-like Disorder Occurring in Children and Young Adults.

OBJECTIVES: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat. METHODS: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU. RESULTS: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1-23] months, and first symptoms occurred 39 [22-106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19-67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). CONCLUSIONS: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.

Effects of prednisolone on behavioral and inflammatory profile in animal model of PTZ-induced seizure.

Epilepsy is a chronic neurological condition that affects 1%-2% of the world population. Although research about the disease is advancing and a wide variety of drugs is available, about 30 % of patients have refractory epilepsy which cannot be controlled with the most common drugs. This highlights the need for a better understanding of the disorder and new types of treatment for it. Against this backdrop, a growing body of evidence has reported that inflammation may play a role both in the origin and in the progression of seizures. It has shown a tendency to be both the root and the result of epilepsy. This investigation aimed to assess the impact of prednisolone, a steroidal anti-inflammatory drug, in an animal model of pentylenetetrazole (PTZ)-induced seizures, at 1 mg/kg and 5 mg/kg doses. We also examined the degree of seizure severity and the modulation of pro-inflammatory cytokines in the treated animals. Four treatment groups were used (saline, diazepam, prednisolone 1 mg/kg, and prednisolone 5 mg/kg) and, in addition to their own daily treatments, subconvulsant doses of pentylenetetrazole (25 mg/kg) were administered every other day during a test protocol that lasted 14 days. After treatment, the cytokines interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured in the animals' sera, hippocampi, and prefrontal cortices. Animals treated with prednisolone presented less severe seizures than the animals in the saline group, and there was a decrease in pro-inflammatory cytokine levels in central structures, but not peripheral ones. In short, an animal model of chemically-induced epileptic seizures was used, in which the animals were treated with doses of prednisolone, and these animals presented less severe seizures than the negative control group (saline), in addition to showing decreased levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, in the hippocampi and prefrontal cortices, but not the sera.

Anxiety and its influence on maternal breastfeeding self-efficacy / Ansiedad y su influencia en la autoeficacia para la lactancia materna / Ansiedade e sua influência na autoeficácia materna para amamentação

Objective: to identify the levels of anxiety and breastfeeding self-efficacy in puerperal women at the intervals of 60, 120, and 180 days postpartum; and to verify the influence of anxiety on breastfeeding self-efficacy among these puerperal women. Method: an analytical, longitudinal and prospective study, conducted with 186 puerperal women, and which used a sociodemographic and obstetric characterization questionnaire, the State-Trait Anxiety Inventory, and the Breastfeeding Self-Efficacy Scale - Short Form. The analyses were performed by means of descriptive statistics, and Fisher's Exact Test was used. Results: most of the puerperal women presented low levels of trait anxiety (55.4%) and of state anxiety (66.2% at 60 days, 72.8% at 120 days, and 75.5% at 180 days), and a high level of self-efficacy (77.3% at 60 days, 75.3% at 120 days, and 72.1% at 180 days of puerperium). Low levels of trait anxiety and state anxiety were associated with high self-efficacy at 60 days (p=0.0142 and p=0.0159, respectively). Conclusion: it is necessary to pay greater attention to the mental health of puerperal women, considering that those who presented low levels of anxiety had higher levels of self-efficacy, a situation that can result in longer exclusive breastfeeding.

Objetivo: identificar los niveles de ansiedad y autoeficacia para la lactancia materna en puérperas a intervalos de 60, 120 y 180 días posparto; verificar la influencia de la ansiedad sobre la autoeficacia para amamantamiento en estas madres. Método: estudio analítico, longitudinal y prospectivo, con 186 puérperas, utilizando un cuestionario sociodemográfico y obstétrico, el Inventario de Ansiedad Rasgo-Estado y la Breastfeeding Self-Eficcacy Scale - Short Form. Los análisis se realizaron mediante estadística descriptiva y se utilizó la prueba exacta de Fisher. Resultados: la mayoría de las puérperas presentaron bajo nivel de ansiedad rasgo (55,4%), bajo nivel de ansiedad estado (66,2% a los 60 días, 72,8% a los 120 días y 75,5% a los 180 días) y alto nivel de autoeficacia (77,3% a los 60 días, 75,3% a los 120 días y 72,1% a los 180 días del puerperio). Los niveles bajos de ansiedad rasgo y ansiedad estado se asociaron con una alta autoeficacia a los 60 días (p=0,0142 y p=0,0159 respectivamente). Conclusión: es necesario prestarle mayor atención a la salud mental de las puérperas, dado que las mujeres que presentaban bajos niveles de ansiedad tenían mayores niveles de autoeficacia, lo que puede implicar un mayor tiempo de lactancia materna exclusiva.

Objetivo: identificar os níveis de ansiedade e da autoeficácia para amamentação entre puérperas nos intervalos de 60, 120 e 180 dias pós-parto; verificar a influência da ansiedade na autoeficácia para amamentação entre essas puérperas. Método: estudo analítico, longitudinal e prospectivo, com 186 puérperas, utilizando-se um questionário de caracterização sociodemográfica e obstétrica, o Inventário de Ansiedade Traço-Estado e a Breastfeeding Self-Eficcacy Scale - Short Form. As análises foram feitas pela estatística descritiva, e utilizado o Teste Exato de Fisher. Resultados: a maioria das puérperas apresentou baixo nível de ansiedade-traço (55,4%), baixo nível de ansiedade-estado (66,2% aos 60 dias, 72,8% aos 120 dias e 75,5% aos 180 dias) e alto nível de autoeficácia (77,3% aos 60 dias, 75,3% aos 120 dias e 72,1% aos 180 dias de puerpério). Baixos níveis de ansiedade-traço e de ansiedade-estado associaram-se com a autoeficácia elevada aos 60 dias (p=0,0142 e p=0,0159 respectivamente). Conclusão: é necessária uma maior atenção à saúde mental das puérperas, considerando que mulheres que apresentaram baixos níveis de ansiedade tiveram maiores níveis de autoeficácia, situação que pode implicar em maior tempo de aleitamento materno exclusivo.

Presence of antigenotoxic and anticytotoxic effects of the chalcone 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one using in vitro and in vivo assays.

Chalcones are chemically defined as α,ß-unsaturated ketones with a 1,3-diphenyl-2-propen-1-one nucleus. These compounds occur naturally in plants and are considered precursors of flavonoids. Given that evaluating genetic toxicology tests is essential in investigating the safe use and chemopreventive potential of different natural and synthetic compounds, this study aimed to assess the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activity of the chalcone 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7ß). The CAB7ß was synthesized via Claisen-Schmidt reaction. The Ames test was applied using the co-treatment model as well as a micronucleus assay of mouse bone marrow with co-, pre- and post-treatment models. Our results indicate no genotoxic effect for CAB7ß in any of the tests applied. At all the concentrations used, CAB7ß showed a significant DNA protective effect against the mutagenic action of 4-nitroquinoline-1-oxide and sodium azide according to the Ames test, and against doxorubicin in the co-, pre- and post-treatment models of the micronucleus assay. CAB7ß alone displayed cytotoxic activity in the micronucleus test. At concentrations of 12,5 and 50 µg/plate, CAB7ß showed a moderate cytotoxic profile only in Salmonella typhimurium strain TA98. However, an anticytotoxic effect was observed against S. typhimurium strain TA100 for all the concentrations tested and during co-, pre- and post-treatment in the micronucleus assay. It was concluded that CAB7ß exhibited a slightly cytotoxic effect in S. typhimurium strain TA98 and significant antigenotoxic and anticytotoxic effects in cells of mouse, making it a promising candidate in chemoprevention and possibly in the development of new cancer treatments.

Pyogenic granuloma of the ampulla of Vater: unexpected cause of gastrointestinal bleeding.

We describe the case of a previously healthy 8-year-old girl presenting with a 1-year history of iron deficiency anemia. There was no report of hematemesis, abdominal pain or melena. Laboratory work-up excluded iron malabsorption as the underlying cause. Therefore, endoscopic evaluation was performed to exclude gastrointestinal blood loss, which revealed the presence of a 7 mm reddish lesion located within the ampulla of Vater. Capsule endoscopy excluded alternative diagnoses and concomitant lesions. Histopathological examination confirmed the diagnosis of pyogenic granuloma. The young age of the child and the benign nature of this lesion along with the absence of complications favored conservative management. Pyogenic granuloma is a benign vascular lesion that presents as a polypoid red mass. In the gastrointestinal tract, it is a rare condition and occurs more commonly in the elderly. The most common sites are the small intestine, esophagus, and colon, but they can occur throughout the entire gastrointestinal tract with a propensity to bleed that may cause iron deficiency anemia. In pediatric age patients, there are few reports of gastrointestinal pyogenic granulomas, most of which occur in the colon and rectum. Its identification and location in the ampulla of Vater is an exceptional finding.

Optical properties and antiangiogenic activity of a chalcone derivate.

Chalcones and their derivatives exhibit numerous pharmacological activities such as antibacterial, antifungal, cytotoxic, antinociceptive and anti-inflammatory. Recently, they have been assessed aiming for novel application in nonlinear optics and in the treatment of immune diseases and cancers. In this study, we investigate the optical properties of synthetic chalcona 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7ß) and its antiangiogenic potential using the chorioallantoic membrane (CAM) with the S180 sarcoma cell line. Experimental and theoretical results show intense absorption in the UVA-UVC region, which is associated with a π → π* transition with intramolecular charge transfer from the trimethyl-cyclohexen-1-yl ring to the chlorophenyl ring. Quantum chemical calculations of the first hyperpolarizability, accounting for both solvent and frequency dispersion effects, are in very good concordance with hyper-Rayleigh scattering measurements. In addition, two-photon absorption allowed band centered at 650 nm was observed. Concerning antiangiogenic activity, CAB7ß causes a significant reduction in the total number, junctions, length and caliber of blood vessels stimulated by S180 cells reducing the presence of blood vessels, inflammatory cells and others elements related to angiogenic process. It is found that CAB7ß is a versatile compound and a promising candidate for linear and nonlinear optical applications, in therapy against sarcoma and phototherapy.

Cigarette smoke directly impairs skeletal muscle function through capillary regression and altered myofibre calcium kinetics in mice.

KEY POINTS: Cigarette smoke components directly alter muscle fatigue resistance and intracellular muscle fibre Ca2+ handling independent of a change in lung structure. Changes in muscle vascular structure are associated with a depletion of satellite cells. Sarcoplasmic reticulum Ca2+ uptake is substantially impaired in myofibres during fatiguing contractions in mice treated with cigarette smoke extract. ABSTRACT: Cigarette smokers exhibit exercise intolerance before a decline in respiratory function. In the present study, the direct effects of cigarette smoke on limb muscle function were tested by comparing cigarette smoke delivered to mice by weekly injections of cigarette smoke extract (CSE), or nose-only exposure (CS) 5 days each week, for 8 weeks. Cigarette smoke delivered by either route did not alter pulmonary airspace size. Muscle fatigue measured in situ was 50% lower in the CSE and CS groups than in control. This was accompanied by 34% and 22% decreases in soleus capillary-to-fibre ratio of the CSE and CS groups, respectively, and a trend for fewer skeletal muscle actin-positive arterioles (P = 0.07). In addition, fewer quiescent satellite cells (Nes+Pax7+) were associated with soleus fibres in mice with skeletal myofibre VEGF gene deletion (decreased 47%) and CS exposed (decreased 73%) than with control fibres. Contractile properties of isolated extensor digitorum longus and soleus muscles were impaired. In flexor digitorum brevis myofibres isolated from CSE mice, fatigue resistance was diminished by 43% compared to control and CS myofibres, and this was accompanied by a pronounced slowing in relaxation, an increase in intracellular Ca2+ accumulation, and a slowing in sarcoplasmic reticulum Ca2+ uptake. These data suggest that cigarette smoke components may impair hindlimb muscle vascular structure, fatigue resistance and myofibre calcium handling, and these changes ultimately affect contractile efficiency of locomotor muscles independent of a change in lung function.

The involvement of RUNX2 and SPARC genes in the bacterial chondronecrosis with osteomyelitis in broilers.

Economic losses due to an increase of leg disorders in broilers have become a major concern of the poultry industry. Despite the efforts to reduce skeletal abnormalities in chickens, insufficient progress has been made. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main disorders that affect bone integrity in broilers. However, the genetic pathways and genes involved in most bone problems, including BCO, remains unclear. In this study, femoral samples from male broilers with 45 days of age affected or not with BCO were used to compare the relative expression with a reverse transcription real time PCR approach of 13 candidate genes: SPP1 (osteopontin), TNFRSF11B (osteoprotegerin), SPARC (osteonectin), CALB1 (calbidin 1), CALM (Calmodulin 2), IBSP (sialoprotein), COL1A2 (collagen, type I, α 2), BMP2 (bone morphogenetic protein 2), BMP3 (bone morphogenetic protein 3), RANKL (κ-B nuclear factor ligand), SMAD1 (SMAD family member 1), LEPR (leptin receptor) and RUNX2 (related transcription factor Runt 2). Differential expression test between affected and non-affected groups was performed using the REST software. The RUNX2 and SPARC genes were downregulated (P<0.05) in the affected group, with reduced expression of fourfold when compared with the non-affected group. This result indicates that the downregulation of RUNX2 and SPARC can contribute to an increased incidence of BCO in broilers.

S-Nitrosylation of Sarcomeric Proteins Depresses Myofilament Ca2+)Sensitivity in Intact Cardiomyocytes.

AIMS: The heart responds to physiological and pathophysiological stress factors by increasing its production of nitric oxide (NO), which reacts with intracellular glutathione to form S-nitrosoglutathione (GSNO), a protein S-nitrosylating agent. Although S-nitrosylation protects some cardiac proteins against oxidative stress, direct effects on myofilament performance are unknown. We hypothesize that S-nitrosylation of sarcomeric proteins will modulate the performance of cardiac myofilaments. RESULTS: Incubation of intact mouse cardiomyocytes with S-nitrosocysteine (CysNO, a cell-permeable low-molecular-weight nitrosothiol) significantly decreased myofilament Ca(2+) sensitivity. In demembranated (skinned) fibers, S-nitrosylation with 1 µM GSNO also decreased Ca(2+) sensitivity of contraction and 10 µM reduced maximal isometric force, while inhibition of relaxation and myofibrillar ATPase required higher concentrations (≥ 100 µM). Reducing S-nitrosylation with ascorbate partially reversed the effects on Ca(2+) sensitivity and ATPase activity. In live cardiomyocytes treated with CysNO, resin-assisted capture of S-nitrosylated protein thiols was combined with label-free liquid chromatography-tandem mass spectrometry to quantify S-nitrosylation and determine the susceptible cysteine sites on myosin, actin, myosin-binding protein C, troponin C and I, tropomyosin, and titin. The ability of sarcomere proteins to form S-NO from 10-500 µM CysNO in intact cardiomyocytes was further determined by immunoblot, with actin, myosin, myosin-binding protein C, and troponin C being the more susceptible sarcomeric proteins. INNOVATION AND CONCLUSIONS: Thus, specific physiological effects are associated with S-nitrosylation of a limited number of cysteine residues in sarcomeric proteins, which also offer potential targets for interventions in pathophysiological situations.