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O ivermectin, antiparasitário amplamente utilizado em caprinos jovens, foi avaliado sobre nematódeos gastrintestinais, em todas as fases parasitárias. Doze caprinos jovens, naturalmente parasitados foram utilizados no experimento, sendo um grupo de seis animais medicado com ivermectin, na dose de 200µg.kg-1 v.o. e o outro grupo utilizado como controle. Para a avaliação, utilizou-se o teste de redução na contagem de ovos (FECR), redução de larvas infectantes e carga parasitária. Amostras fecais de caprinos foram coletadas no dia da medicação (dia zero), aos sete e catorze dias. No décimo quarto dia pós-medicação, todos os caprinos foram sacrificados, para a coleta de helmintos e cálculo da carga parasitária total. A redução do número de ovos (FECR) e a eficácia sobre adultos foi de 42,10 % e 32,62 %, respectivamente.O gênero Haemonchus representou 100 % da população do grupo medicado e 99,58 % do grupo controle. Estes resultados indicam que os caprinos já estavam parasitados por Haemonchus resistente ao ivermectin.

Purinergic signaling plays a role in the pathophysiology of different viral infections. Recently, we showed that COVID-19 increases extracellular ATP levels, which may amplify the pro-inflammatory signals in the disease. The P2X7 receptor can be a protagonist in the pro-inflammatory responses. Herein, we investigated the role of the P2X7 receptor in the lung immune response triggered by inoculation of inactivated SARS-CoV-2 (iSARS-CoV-2) in K18-Human ACE2 transgenic mice. Pharmacological inhibition of the P2X7 receptor was performed with intraperitoneal administration of 50 mg/kg of Brilliant Blue G (BBG) one day before viral inoculation. Animals were divided into four groups: a control group (MOCK), a group inoculated with the inactivated virus iSARS-CoV-2, a BBG-treated control group (MOCK + BBG), and a BBG-treated inoculated group (iSARS-CoV-2 + BBG). Virus inoculation was intratracheal with 50 µl of mock or 2 × 10 6 Plaque Forming Units (PFU) of iSARS-CoV-2. After three days, blood and lungs were collected. We found a significant increase in ATP and LDH in serum and mRNA levels of P2X7 and P2Y 12 receptors, CD39, IL-1β, and TNF-α in the lung of the iSARS-CoV-2 group when compared with the control group. BBG treatment attenuated these increases. Lung histological analyses showed severe lung damage in the iSARS-CoV-2 group, which was reduced by the BBG treatment. Immunohistochemical staining confirmed the increased presence of P2X7, P2Y 12 , and CD39 proteins in the iSARS-CoV-2 vs. the MOCK group. Thus, P2X7 receptor inhibition decreases iSARS-CoV-2-induced lung inflammation, indicating that this receptor might contribute to SARS-CoV-2 pathology., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The Institutional Animal Care and Use Committee of the Federal University of Rio de Janeiro (protocol number 088/21) reviewed and approved the animal study., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The effects of methylmercury (MeHg) on exposed populations are a public health problem. In contrast to widely studied neurological damage, few cardiovascular changes have been described. Our group evaluated the cardiotoxicity of a cumulative dose of 70 mg.kg -1 fractioned over a 14-day exposure period in mice (MeHg70 group). The effects of MeHg on proteins relevant to cardiac mitochondrial function were also investigated. The results obtained showed a reduction in oxygen consumption in the two settings. In cardiac tissue samples in oxygraphy studies, this reduction was related to a lower efficiency of complexes II and V, which belong to the oxidative phosphorylation system. In vivo, mice in the MeHg70 group presented lower oxygen consumption and running tolerance, as shown by ergometric analyses. Cardiac stress was evident in the MeHg70 group, as indicated by a marked increase in the level of the mRNA encoding atrial natriuretic peptide. Electrocardiogram studies revealed a lower heart rate at rest in the animals from the MeHg70 group, as well as prolonged left ventricular depolarisation and repolarisation. Through echocardiographic analysis, reductions in the left ventricular ejection fraction and left ventricular wall thickness of approximately 10% and 20%, respectively, were detected. These results indicate that the oral intake of MeHg can decrease cardiac function and oxidative metabolism. This finding highlights the importance of monitoring MeHg levels in humans and animals in contaminated areas, as well as periodically carrying out cardiac function tests.

Introduction: Sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: Sepsis was induced in wild-type (WT), P2X7 -/- , and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7 -/- sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba -1 ) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7 -/- sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: The modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsis-associated encephalopathy, being considered an important therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alves, Silva, Rodrigues, Araújo, Gouvêa, Leite-Aguiar, Santos, Silva, Ferreira, Marques, Passos, Maron-Gutierrez, Kurtenbach, da Costa, Figueiredo, Wyse, Coutinho-Silva and Savio.)

Introduction: Trophoblastic neoplasia is detected in approximately 25% of complete hydatidiform moles (CMs) and 0.5% of partial hydatidiform moles (PMs). Hydatidiform mole (HM) subtyping is important to properly monitor and predict patient outcomes. Ploidy studies generally involve diploid CMs and triploid PMs. P57KIP2, expressed in the maternal genome, is usually not detected in CM. We determined whether HER2 FISH and p57 immunostaining contributed to the histopathological classification of HMs., Methods: This retrospective cohort study focused on patients diagnosed with HM by histopathological examination who were followed up at a trophoblastic disease center from 2002 to 2017. Pathological samples of 108 products of conception were reviewed and reclassified according to detailed criteria. Tissue microarray technology (TMA) was used for p57 KIP2 immunostaining and HER2 FISH analysis., Results: Histopathological review showed 57 (53%) CMs, 47 (43%) PMs and 4 (4%) inconclusive cases. P57 immunostaining revealed 59 (55%) negative and 22 (20%) positive specimens, and 27 (25%) were inadequate for analysis. FISH HER2 detected 68 (63%) diploid and 33 (30%) triploid cases; two (2%) had oncogene amplification. The three strategies led to a diagnostic change in 28 samples (26%). The final diagnosis was CM in 75 cases (70%) and PM in 30 (28%); three cases remained inconclusive., Discussion: TMA is a cost-saving method that allows the simultaneous study of large case series. The combination of histopathology, HER2 FISH and p57 tests can be useful for accurately differentiating CM and PM, thus providing additional information on disease prognosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Gouvêa, AL, Martinez, CG, and Kurtenbach, E. Determining maximal muscle strength in mice: validity and reliability of an adapted swimming incremental overload test. J Strength Cond Res 34(8): 2360-2368, 2020-At present, there are no reliable methods to determine maximal muscle strength in small rodents. Here, we established an adapted swimming incremental overload test (SIOT) as an instrument for this purpose. First, to validate the test, BALB/c mice received 20 mg·kg·d of dexamethasone (DEXA group) or water (control group). After 14 days, with a cumulative dose of 120 mg·kg of dexamethasone, the SIOT could detect a decrease of approximately 7% in muscle strength. In addition, this decrease was consistent with a significant reduction in body (above 13.5%) and muscle (approximately 15%) weight in DEXA atrophic animals. To establish the SIOT reliability, another group of animals was evaluated for 5 consecutive days. In this second protocol, the SIOT was executed with an initial load corresponding to 12% of the mouse body weight (BW) fixed to the tail. Increments between 1 and 5% of the BW were added during each attempt to obtain the highest load that was tolerated for a time interval of 5-7 seconds. On the last day, the SIOT reliability test was performed by 2 different raters to obtain the inter-rater reproducibility. The adapted SIOT was shown to be reliable when measured by the same rater (intraclass correlation coefficient [ICC] = 0.939) and by 2 different raters (ICC = 0.830). The Bland-Altman graphical representation did not demonstrate heteroscedastic errors. Therefore, the SIOT proved to be a sensitive and reliable method to measure muscle strength, and it can be applied to small animals in different models of muscle atrophy.

Background: In the photodynamic therapy (PDT), the photosensitizer absorbs light and transfers the energy of the excited state to the oxygen in the cell environment producing reactive oxygen species (ROS), that in its turn, may cause cell damage. In the photothermal therapy (PTT), light also is responsible for activating the photothermal agent, which converts the absorbed energy in heat. Graphene oxide is a carbon-based material that presents photothermal activity. Its physical properties allow the association with the photosensitizer methylene blue and consequently the production of ROS when submitted to light irradiation. Therefore, the association between nanographene oxide and methylene blue could represent a strategy to enhance therapeutic actions. In this work, we report the nanographene oxide-methylene blue platform (NanoGO-MB) used to promote tumor ablation in combination with photodynamic and photothermal therapies against a syngeneic orthotopic murine breast cancer model., Results: In vitro, NanoGO-MB presented 50% of the reactive oxygen species production compared to the free MB after LED light irradiation, and a temperature increase of ~ 40 °C followed by laser irradiation. On cells, the ROS production by the nanoplatform displayed higher values in tumor than normal cells. In vivo assays demonstrated a synergistic effect obtained by the combined PDT/PTT therapies using NanoGO-MB, which promoted complete tumor ablation in 5/5 animals. Up to 30 days after the last treatment, there was no tumor regrowth compared with only PDT or PTT groups, which displayed tumoral bioluminescence 63-fold higher than the combined treatment group. Histological studies confirmed that the combined therapies were able to prevent tumor regrowth and liver, lung and spleen metastasis. In addition, low systemic toxicity was observed in pathologic examinations of liver, spleen, lungs, and kidneys., Conclusions: The treatment with combined PDT/PTT therapies using NanoGO-MB induced more toxicity on breast carcinoma cells than on normal cells. In vivo, the combined therapies promoted complete tumor ablation and metastasis prevention while only PDT or PTT were unable to stop tumor development. The results show the potential of NanoGO-MB in combination with the phototherapies in the treatment of the breast cancer and metastasis prevention.

Background: Urine monitoring programs represent an important strategy for early diagnosis of reactivation of BK polyomavirus (BKV) in kidney transplant recipients. This study analyzes a BKV urine screening model in kidney transplant patients., Methods: Urinary screening for BKV reactivation was performed by urinary decoy cell and polymerase chain reaction (PCR) tests in samples from 32 consecutive kidney transplant patients, collected in a 6-month follow-up period. PCR in plasma samples and BKV immunohistochemical studies to assess BKV renal disease, if a kidney biopsy was indicated, were performed., Results: The urinary screening for BKV among 32 renal receptors was positive in 18 patients (56%) by the concomitant use of the decoy cells and/or qualitative PCR at some time during the study period. Transfusion before transplantation was significantly associated with urinary decoy cell positive screening (odds ratio = 11; 95% confidence interval = 1.47 to 82.4; P < .05); and so was male sex (odds ratio = 2.02; 95% confidence interval = 1.07 to 3.83; P < .05). The clinical management of screening positive cases consisted of decreasing or changing the immunosuppression regimen. Sixteen renal biopsies were performed. Immunohistochemistry for SV40 T antigen was negative in all biopsies. After 1 year of follow-up, no patient developed BKV-associated nephropathy, and there was no difference in renal function between patients positive and negative for BKV urinary screening., Conclusions: Early urinary monitoring is effective in detection of BKV replication and represents a good strategy to minimize the deleterious effects caused by the presence of the virus on preservation of graft function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this meta-analytic review was to examine the extent and quality of research on the post-activation potentiation acute effect of rest interval manipulation on jumping performance. This manuscript adopted the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Criteria eligibility included crossover, randomised, non-randomised and counterbalanced studies that observed the voluntary muscle action-induced post-activation potentiation on jumping performance. Fourteen studies selected by two independent raters were included in the analysis. The rest intervals involved ranges including 0-3, 4-7, 8-12 and ≥16 min. The results demonstrated medium effect sizes for rest intervals 0-3 and 8-12 min (-0.25, confidence interval (CI): -0.51 to 0.01 for 0-3 min; 0.24, CI: -0.02 to 0.49 for 8-12 min) and a small effect for other ranges (0.15, CI: -0.08 to 0.38 for 4-7 min; 0.07, CI: -0.21 to 0.24 for ≥16 min). There was no evidence of heterogeneity for sub-groups (I2 = 0%; P < 0.001) and no indication of publication bias (Egger's test, P = 0.179). While a rest interval of 0-3 min induced a detrimental effect on jump performance, the range including 8-12 min had a beneficial impact on jump height. Findings suggest that the rest interval manipulation seems to affect post-activation potentiation magnitude and jump height.

Background: In the past, isometric exercises were proscribed for heart disease. However, recent evidence suggests that an isometric handgrip training (IHT) protocol - four sets of two minutes at 30% of maximum strength - produces favorable effects on the autonomic modulation and reduces resting systolic (SBP) and diastolic (DBP) blood pressure., Objective: Aiming at obtaining support for broad clinical applicability, we quantified the main hemodynamic responses during an IHT session in patients from a supervised physical exercise program., Methods: Forty-one patients (36 men) underwent the IHT with measurements of heart rate (HR) and BP before, during each of the two series performed with the left arm and one minute after completion. Measurements were obtained by an electrocardiogram signal in a digital Tango + oscillometric tensiometer, previously validated for physical exercise conditions., Results: The IHT was appropriately carried out, with no clinical adverse reactions. There was a small increase in SBP and DBP levels, respectively, of 16 and 7 mmHg (p <0.05) and an even smaller increase in HR - 3 bpm - (p <0.05) when we compared the data obtained at 80 seconds of the last series with the pre-exercise, Conclusion: IHT was well tolerated by patients undergoing exercise programs, resulting in a transient and modest hemodynamic effect, without inducing rapid cardiac vagal inactivation, characteristic of dynamic and short exercises.

A new system for energy-resolved X-ray fluorescence imaging using a microhole and strip plate (MHSP), a new type of micropattern gas detector (MPGD), is proposed. It works as a single photon counting detector with position and energy detection capability. The interaction of X-rays with the gas medium produces electrons via the photoelectric effect, and the number of electrons is proportional to the absorbed X-ray energy. These electrons are further multiplied in the MHSP. Position detection is achieved using the charge division method. The detector has an active area of 28 x 28 mm(2) and shows good position resolution, about sigma = 125 microm, an intrinsic energy resolution of about 14% FWHM for 5.9 keV X-rays, and a counting rate capability of up to 0.5 MHz. The system has shown good properties for energy-dispersive X-ray fluorescence (EDXRF) applications, since it allows efficient energy and position detection of fluorescence X-rays from multielemental samples. In this work, the system was used to study lead depth distributions in eighteenth-century Portuguese faiences from the Santa Clara-a-Velha monastery. The fluorescence images were obtained by irradiating the samples, with a pinhole placed between the sample and the detector to focus the radiation into the detector. The results are presented here, including the elemental map distributions for different samples.

Condyloma acuminatum is one of the clinical manifestations of papillomavirus infection. The classical histopathological features are already known and do not constitute a diagnostic problem. Clinically, it has been classified into growth or proliferative, full-expression, and regressive or persistent phases, with the histopathological aspects of these distinct phases being well documented in equine cutaneous papillomas. We have designed a protocol of histopathological analysis in order to investigate the possibility of identifying the evolutional phases in human condylomata acuminata. Sixty condylomata acuminata from the files of the Department of Pathology, Universidade Federal Fluminense, were studied regarding koilocytosis, paraceratosis, acantosis, basal cell hyperplasia and mononuclear cell infiltrate. After an individual analysis and comparison of the cases, the main differential aspects of condyloma acuminatum were: koilocytosis, transepithelial lymphocytic infiltrate and basal cell hyperplasia. Thus, condylomatous lesions can be histopathological differentiated in three major patterns: proliferative, viral replication activity and regressive.