Protective Role of Rosmarinic Acid in Experimental Urolithiasis: Understanding Its Impact on Renal Parameters.

This study aimed to assess the ability of rosmarinic acid (RA) to prevent kidney stone formation in an ethylene glycol and ammonium chloride (EG/AC) model. There was an increase in diuresis in the normotensive (NTRs) and hypertensive rats (SHRs) treated with hydrochlorothiazide (HCTZ) and exposed to EG/AC, while RA restored urine volume in NTRs. The EG/AC groups exhibited lower urine pH and electrolyte imbalance; these parameters were not affected by any of the treatments. Both HCTZ+EG/AC and RA+EG/AC reduced calcium oxalate crystal formation in NTR and SHR urine. Kidney tissue analysis revealed alterations in oxidative stress and inflammation parameters in all EG/AC-receiving groups, with RA enhancing antioxidant defenses in SHRs. Additionally, crystals were found in the kidney histology of all EG/AC-exposed groups, with reduced Bowman's capsule areas in NTRs and SHRs. The NTR VEH+EG/AC group showed intense renal damage, while the others maintained their structures, where treatments with HCTZ and RA were fundamental for kidney protection in the NTRs. Docking analysis showed that RA exhibited good binding affinity with matrix metalloproteinase-9, phosphoethanolamine cytidylyltransferase, and human glycolate oxidase enzymes. The data disclosed herein underscore the importance of further research to understand the underlying mechanisms better and validate the potential of RA for clinical use.

Reliability and reference values for diaphragmatic excursion, thickness, and thickening fraction and quadriceps femoris muscle thickness in full-term newborns evaluated by ultrasound.

To determine the diaphragm thickness, thickening fraction, and excursion and thickness of the quadriceps femoris muscle in full-term newborns and to evaluate the intra- and interrater reliability of these measurements. This was a prospective, observational clinical study including full-term newborns born within the first 48 h after birth. Serial measurements of the thickness, thickening fraction, and mobility of the diaphragm muscles and the thickness of the quadriceps muscle were obtained using ultrasound images. A total of 69 newborns with a mean gestational age of 39 weeks were included. The following measurements were obtained and are expressed as the mean (standard deviation): inspiratory diaphragm thickness, 0.19 cm (0.04); expiratory diaphragm thickness, 0.16 cm (0.04); diaphragm thickness fraction, 16.70 cm (10.27); diaphragmatic excursion, 0.68 cm (0.22); and quadriceps thickness, 0.99 cm (0.14). Intrarater reliability was assessed using intraclass correlation coefficients (ICCs). Excellent intrarater agreement was observed for the two groups of operators (ICC > 0.86, p < 0.001) for all measurements except for the diaphragm thickening fraction, which showed good agreement for both operator groups (ICC = 0.70, p < 0.001). Regarding interrater reliability, moderate agreement between the raters was observed in the means of all measures (ICC > 0.49, p < 0.001), except for the diaphragm thickening fraction, which showed poor agreement.    Conclusion: Good intrarater and moderate interrater reliability were achieved in ultrasound evaluations of the thickness and mobility of the diaphragm and quadriceps femoris muscles in full-term newborns, demonstrating the feasibility of this technique for clinical use. This pioneering study offers reference values for these muscles in a single study, allowing comparisons between different clinical conditions. What is Known: • Ultrasound is a highly reliable tool for muscle assessment that can be used to assess muscular atrophy in critically ill patients. • Muscle atrophy worsens the patient's condition and has been associated with worse outcomes. What is New: • To our knowledge, this is the first study to jointly evaluate the diaphragm and quadriceps muscle thickness and evaluate the reliability of all measurements. • Our study presents reference values for both muscles, enabling comparisons between different clinical conditions.

The ticking clock in the dark: Review of biological rhythms in cave invertebrates.

Circadian clocks, internal mechanisms that generate 24-hour rhythms, play a crucial role in coordinating biological events with day-night cycles. In light-deprived environments such as caves, species, particularly isolated obligatory troglobites, may exhibit evolutionary adaptations in biological rhythms due to light exposure. To explore rhythm expression in these settings, we conducted a comprehensive literature review on invertebrate chronobiology in global subterranean ecosystems, analyzing 44 selected studies out of over 480 identified as of September 2023. These studies revealed significant taxonomic diversity, primarily among terrestrial species like Coleoptera, with research concentrated in the United States, Italy, France, Australia, and Brazil, and a notable gap in African records. Troglobite species displayed a higher incidence of aperiodic behavior, while troglophiles showed a robust association with rhythm expression. Locomotor activity was the most studied aspect (>60%). However, approximately 4% of studies lacked information on periodicity or rhythm asynchrony, and limited research under constant light conditions hindered definitive conclusions. This review underscores the need to expand chronobiological research globally, encompassing diverse geographical regions and taxa, to deepen our understanding of biological rhythms in subterranean species. Such insights are crucial for preserving the resilience of subsurface ecosystems facing threats like climate change and habitat loss.

A flow cytometry-based assay to measure neutralizing antibodies against SARS-CoV-2 virus.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has highlighted the need for serological assays that can accurately evaluate the neutralizing efficiency of antibodies produced during infection or induced by vaccines. However, conventional assays often require the manipulation of live viruses on a level-three biosafety (BSL3) facility, which presents practical and safety challenges. Here, we present a novel, alternative assay that measures neutralizing antibodies (NAbs) against SARS-CoV-2 in plasma using flow cytometry. This assay is based on antibody binding to the S protein and has demonstrated precision in both intra- and inter-assay measurements at a dilution of 1:50. The cut-off was determined using Receiver Operating Characteristic (ROC) analysis and the value of 36.01% has shown high sensitivity and specificity in distinguishing between pre-pandemic sera, COVID-19 patients, and vaccinated individuals. The efficiency significantly correlates with the gold standard test, PRNT. Our new assay offers a safe and efficient alternative to conventional assays for evaluating NAbs against SARS-CoV-2.

[Brazilian Ministry of Health strategy to increase vaccination coverage at bordersEstrategia del Ministerio de Salud de Brasil para aumentar las tasas de cobertura de vacunación en las fronteras]. / Estratégia do Ministério da Saúde do Brasil para aumento das coberturas vacinais nas fronteiras.

Objective: Evaluate the implementation of the Ministry of Health's "Action Plan: Border Vaccination Strategy - Agenda 2022" in the Brazil's 33 twin cities and evaluate the increase in the country's vaccination coverage (VC). Methodology: Pre-post community clinical trial. Implementation of the strategy was analyzed, and pre- and post-intervention VC were compared in two stages: P1 (pre-intervention) and P2 (post-intervention). Based on statistical analyses of P1 and P2 coverage, calculations were made of municipal averages, standard deviation, and difference in VC between the two periods. Results: Integration was observed between the primary health care (PHC), surveillance, immunization, and special indigenous health district (DSEI) teams, although there were difficulties, for example, in relation to migratory flows. While immigration flows present challenges in the areas of immunization, PHC, and DSEI, the difficulties are compounded by the polarization of these services, which hinders intersectoral integration. After carrying out the workshops, a total of 50 977 doses were administered in the general population in the 33 twin cities. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, which may be relevant in terms of increasing VC in Brazil. Conclusion: There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, helping to increase VC in Brazil.

Objetivo: Evaluar la aplicación de la Estrategia de Vacunación en las Fronteras - Agenda 2022, que forma parte del Plan de Acción del Ministerio de Salud en las 33 ciudades hermanas y evaluar el aumento de las tasas de cobertura de vacunación en Brasil. Métodos: Ensayo clínico comunitario realizado antes y después de la intervención correspondiente. Se analizó la aplicación de la estrategia y se compararon las tasas de cobertura de vacunación antes y después de la intervención en dos periodos: P1 (pre-intervención) y P2 (post-intervención). En los análisis estadísticos de la tasa de cobertura de vacunación en P1 y P2 se calcularon los valores de media y desviación estándar de los municipios y la diferencia entre las tasas de cobertura de los dos periodos. Resultados: Se observó una integración entre los equipos de Atención Primaria de Salud, Vigilancia, Inmunización y el Distrito Especial de Salud Indígena (DISEI), pero con dificultades, como las inherentes al flujo migratorio. Cabe destacar que el flujo migratorio es uno de los desafíos en el contexto de la inmunización, la atención primaria de salud y el DISEI, dificultad que se ve agravada por la polarización entre los servicios (inmunización, atención primaria de salud y el DISEI), lo que supone un reto para la integración de los sectores. Por lo que respecta al análisis de las tasas de cobertura de vacunación llevado a cabo después de realizar los talleres, se administró un total de 50 977 dosis a la población general en las 33 ciudades hermanas de Brasil. Hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados después de la intervención, lo que puede ser importante para aumentar las tasas de cobertura de Brasil. Conclusión: Después de la intervención hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados, lo cual influyó en el incremento de las tasas de cobertura de Brasil.

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis.

BACKGROUND: Diclofenac is the non-steroidal anti-inflammatory drug (NSAID) mostly prescribed worldwide, but it is highly associated with hypertension and acute kidney injury. Despite that, little information is available about the renal effects of diclofenac in hypertensive individuals, which led us to carry out this comparative study between the renal effects of this NSAID in normotensive (NTR) and spontaneously hypertensive rats (SHR). METHODS: Male Wistar NTR and SHR were orally treated with vehicle (V: 10 mL/kg) or diclofenac sodium (D: 100 mg/kg) once a day for 3 days. Urine volume, electrolytes excretion (Na+, K+, Cl-, and Ca2+), urea, creatinine, pH, and osmolarity were evaluated. Furthermore, blood samples and renal tissue were collected to perform biochemical and histological analysis. RESULTS: Diclofenac increased the renal corpuscle and bowman's space in the SHR, while no microscopic changes were observed in the renal tissue of NTR. Regarding the urinary parameters, diclofenac reduced urine volume, pH, osmolarity, and all electrolytes excretion, followed by decreased urea and creatinine levels in both lineages. Moreover, it also induced hyponatremia, hypokalemia, and hypocalcemia in SHR, while reduced glutathione-S-transferase activity, lipid hydroperoxides, and nitrite levels in renal tissue. CONCLUSIONS: The data presented herein demonstrated that diclofenac induces renal damage and impaired renal function in both NTR and SHR, but those effects are exacerbated in SHR, as seen by the histological changes and electrolytes balance disturbance, therefore, reinforcing that diclofenac may increase the risks of cardiovascular events in hypertensive patients.

Vasodilation and Blood Pressure-Lowering Effect of 3-Demethyl-2-Geranyl-4-Prenylbellidifoline, a Xanthone Obtained from Garcinia achachairu, in Hypertensive Rats.

3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu, has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings. The non-selective muscarinic receptor antagonist (atropine), the non-selective inhibitor of nitric oxide synthase (L-NAME), as well as the inhibitor of soluble guanylate cyclase (ODQ) altogether avoided DGP-induced relaxation. Tetraethylammonium (small conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), and barium chloride (an influx-rectifying K+ channel blocker) significantly reduced DGP capacity to induce relaxation without the interference of glibenclamide (an ATP-sensitive inward rectifier 6.1 and 6.2 K+ channel blocker). Additionally, administration of DGP, 1 mg/kg i.v., decreased the mean, systolic, and diastolic arterial pressures, and the heart rate of SHRs. The natural xanthone DGP showed promising potential as an endothelium-dependent vasorelaxant, operating through the nitric oxide pathway and potassium channels, ultimately significantly reducing blood pressure in hypertensive rats.

Naringen's Effects on Diuresis and Prevention of Urolithiasis in Hypertensive Rats.

This research demonstrates the diuretic effect of naringenin, a flavanone aglycone found in citrus, on spontaneously hypertensive female and male rats (SHR). The data reinforces existing literature findings that male SHR exhibits higher systolic blood pressure than age-matched females. Urine volume assessed over 8 hours was lower when obtained from SHR males than females. When these animals were orally treated with different doses of naringenin (0.1-1 mg/kg), this increased urinary volume in both genders at the highest dose tested. In contrast, the lowest dose promoted a significant natriuretic effect. The other electrolytes analyzed in urine were not significantly altered, except potassium excretion, which was shown to be increased in the urine of SHR males. Furthermore, naringenin showed promise in reducing calcium oxalate (CaOx) crystal formation in an in vitro model, presenting potential advantages in lithiasis prevention.

3-Demethyl-2-geranyl-4-prenylbellidifoline, a natural xanthone with diuretic and kidney protective properties.

OBJECTIVES: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats. METHODS: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis. KEY FINDINGS: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-ß-D-glucosaminidase activity and nitrite levels. CONCLUSION: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone.

A new cave-dwelling species of Charinus (Amblypygi: Charinidae) from northern Brazil.

We present the description and illustration of a new species within the genus Charinus Simon, 1892, discovered in a cave located in the state of Tocantins, situated in the northern region of Brazil. Charinus tocantinensis sp. nov., can be distinguished from its congeners by the following combination of distinctive characters: pedipalp femur with four dorsal spines and four ventral spines; well-developed median eyes and median ocular tubercle; female gonopods sucker-like, slightly longer than wide, opening rounded and margins with fold with each a small posterior slit; cheliceral claw with ten denticles. In addition to the species description, we have included a key for identifying Charinus species in Brazil, along with a distribution map that highlights the known species in the country. This newly described species marks the first formal documentation of a Charinus species within the state of Tocantins. With the addition of this species, the global tally of recognized Charinus species now stands at 98, and Brazil, in particular, is home to a total of 44 formally described species within this genus.

Estratégia do Ministério da Saúde do Brasil para aumento das coberturas vacinais nas fronteiras / Brazilian Ministry of Health strategy to increase vaccination coverage at borders / Estrategia del Ministerio de Salud de Brasil para aumentar las tasas de cobertura de vacunación en las fronteras

RESUMO Objetivo. Avaliar a implementação de estratégia do "Plano de Ação: Estratégia de Vacinação nas Fronteiras - Agenda 2022" do Ministério da Saúde nas 33 cidades gêmeas e avaliar o incremento das coberturas vacinais (CV) brasileiras. Métodos. Ensaio clínico comunitário, do tipo antes e depois. Analisou-se a realização da estratégia, bem como comparadas as CV pré e pós-intervenção em dois tempos: P1 (pré-intervenção) e P2 (pós-intervenção). Análises estatísticas sobre a CV, no P1 e P2, foram calculados os valores de média entres os municípios, desvio padrão e diferença entre as coberturas dos dois períodos. Resultados. Observou-se integração entre as equipes de Atenção Primária à Saúde (APS), Vigilância, Imunização e Distrito Sanitário Especial Indígena (DSEI), porém com dificuldades, como aquelas inerentes ao fluxo migratório. Ressalta-se que o fluxo imigratório é um dos desafios no contexto da imunização, APS e DSEI, entretanto, a esta dificuldade soma-se a polarização entre os serviços (imunização, APS e DISEI), ocasionando um desafio para a integração dos setores. Em relação à análise das CV, após a realização das oficinas, foram totalizadas 50 977 doses aplicadas na população geral nas 33 cidades-gêmeas do Brasil. Houve incremento das coberturas vacinais de crianças de até um ano de idade nos locais avaliados após a intervenção, o que pode ser importante para aumentar as CV no Brasil. Conclusão. Houve incremento das coberturas vacinais das crianças até um ano de idade nos locais avaliados após a intervenção e isso influenciou no aumento das CV no Brasil.

ABSTRACT Objective. Evaluate the implementation of the Ministry of Health's "Action Plan: Border Vaccination Strategy - Agenda 2022" in the Brazil's 33 twin cities and evaluate the increase in the country's vaccination coverage (VC). Methodology. Pre-post community clinical trial. Implementation of the strategy was analyzed, and pre- and post-intervention VC were compared in two stages: P1 (pre-intervention) and P2 (post-intervention). Based on statistical analyses of P1 and P2 coverage, calculations were made of municipal averages, standard deviation, and difference in VC between the two periods. Results. Integration was observed between the primary health care (PHC), surveillance, immunization, and special indigenous health district (DSEI) teams, although there were difficulties, for example, in relation to migratory flows. While immigration flows present challenges in the areas of immunization, PHC, and DSEI, the difficulties are compounded by the polarization of these services, which hinders intersectoral integration. After carrying out the workshops, a total of 50 977 doses were administered in the general population in the 33 twin cities. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, which may be relevant in terms of increasing VC in Brazil. Conclusion. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, helping to increase VC in Brazil.

RESUMEN Objetivo. Evaluar la aplicación de la Estrategia de Vacunación en las Fronteras - Agenda 2022, que forma parte del Plan de Acción del Ministerio de Salud en las 33 ciudades hermanas y evaluar el aumento de las tasas de cobertura de vacunación en Brasil. Métodos. Ensayo clínico comunitario realizado antes y después de la intervención correspondiente. Se analizó la aplicación de la estrategia y se compararon las tasas de cobertura de vacunación antes y después de la intervención en dos periodos: P1 (pre-intervención) y P2 (post-intervención). En los análisis estadísticos de la tasa de cobertura de vacunación en P1 y P2 se calcularon los valores de media y desviación estándar de los municipios y la diferencia entre las tasas de cobertura de los dos periodos. Resultados. Se observó una integración entre los equipos de Atención Primaria de Salud, Vigilancia, Inmunización y el Distrito Especial de Salud Indígena (DISEI), pero con dificultades, como las inherentes al flujo migratorio. Cabe destacar que el flujo migratorio es uno de los desafíos en el contexto de la inmunización, la atención primaria de salud y el DISEI, dificultad que se ve agravada por la polarización entre los servicios (inmunización, atención primaria de salud y el DISEI), lo que supone un reto para la integración de los sectores. Por lo que respecta al análisis de las tasas de cobertura de vacunación llevado a cabo después de realizar los talleres, se administró un total de 50 977 dosis a la población general en las 33 ciudades hermanas de Brasil. Hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados después de la intervención, lo que puede ser importante para aumentar las tasas de cobertura de Brasil. Conclusión. Después de la intervención hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados, lo cual influyó en el incremento de las tasas de cobertura de Brasil.

Individual and environmental parameters in children with and without developmental coordination disorder: associations with physical activity and body mass index.

Introduction: Physical Activity (PA) is a complex behavior, and the relevance of other factors such as BMI, SES and children's behavior at school and home still lacks investigation for children, especially those at risk or with Developmental Coordination Disorder (DCD). The objective of this study was to examine whether socioeconomic status (SES), school's spaces for children's movement, active play, screen time, motor skill proficiency, perceived motor competence, and engagement in the physical education lessons were associated with PA and BMI in children with typical development (TD), at risk of DCD (r-DCD), and with DCD. Methods: Children (N = 352; 4-10-year-old) from six public schools in a major urban city, in southern of Brazil, were assessed regarding motor skill proficiency (locomotor and ball skills), perceived motor competence, and weight status. PA and engagement in the lesson were assessed using pedometers and a behavior checklist of motor experience of success. Parents recorded the daily time that children spent on screen and in active play. Results: The hierarchical multivariate linear regressions showed that age, sex, SES, Schools with more favorable space for children's movement, locomotor and ball skills, and successful engagement, were associated with PA for children with TD. Age, screen time, locomotor, and successful engagement were associated with BMI. For children at r-DCD, age, sex, SES, with more favorable space for children's movement, and locomotor were associated with PA. Age, active play and screen time were associated with BMI. For children with DCD, sex, SES, Schools with more favorable space for children's movement, screen time, and successful engagement were associated with PA. Age, sex, active play, and screen time were associated with BMI. Conclusion: Different factors were associated with PA and BMI for children with different levels of motor impairment (r-DCD and DCD) and children with TD.

Diuretic, Natriuretic, And Ca2+-Sparing Effect Of The Alkaloid Boldine In Rats.

BACKGROUND: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. METHODS: Wistar rats were used and the urine volume was noted for 8 h and further studied. RESULTS: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ​​remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization. CONCLUSIONS: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.

Role of K+ and Ca2+ Channels in the Vasodilator Effects of Plectranthus barbatus (Brazilian Boldo) in Hypertensive Rats.

Plectranthus barbatus, popularly known as Brazilian boldo, is used in Brazilian folk medicine to treat cardiovascular disorders including hypertension. This study investigated the chemical profile by UFLC-DAD-MS and the relaxant effect by using an isolated organ bath of the hydroethanolic extract of P. barbatus (HEPB) leaves on the aorta of spontaneously hypertensive rats (SHR). A total of nineteen compounds were annotated from HEPB, and the main metabolite classes found were flavonoids, diterpenoids, cinnamic acid derivatives, and organic acids. The HEPB promoted an endothelium-dependent vasodilator effect (~100%; EC50 ~347.10 µg/mL). Incubation of L-NAME (a nonselective nitric oxide synthase inhibitor; EC50 ~417.20 µg/mL), ODQ (a selective inhibitor of the soluble guanylate cyclase enzyme; EC50 ~426.00 µg/mL), propranolol (a nonselective α-adrenergic receptor antagonist; EC50 ~448.90 µg/mL), or indomethacin (a nonselective cyclooxygenase enzyme inhibitor; EC50 ~398.70 µg/mL) could not significantly affect the relaxation evoked by HEPB. However, in the presence of atropine (a nonselective muscarinic receptor antagonist), there was a slight reduction in its vasorelaxant effect (EC50 ~476.40 µg/mL). The addition of tetraethylammonium (a blocker of Ca2+-activated K+ channels; EC50 ~611.60 µg/mL) or 4-aminopyridine (a voltage-dependent K+ channel blocker; EC50 ~380.50 µg/mL) significantly reduced the relaxation effect of the extract without the interference of glibenclamide (an ATP-sensitive K+ channel blocker; EC50 ~344.60 µg/mL) or barium chloride (an influx rectifying K+ channel blocker; EC50 ~360.80 µg/mL). The extract inhibited the contractile response against phenylephrine, CaCl2, KCl, or caffeine, similar to the results obtained with nifedipine (voltage-dependent calcium channel blocker). Together, the HEPB showed a vasorelaxant effect on the thoracic aorta of SHR, exclusively dependent on the endothelium with the participation of muscarinic receptors and K+ and Ca2+ channels.

Dermatoporosis in Upper Limbs Treated With Polymethylmethacrylate Microspheres Using the BioSculpt® Technique.

Dermatoporosis is a syndrome of fragility or chronic cutaneous insufficiency. It presents with localized violaceous spots on the extensor face of the upper limbs of older people, with signs such as senile purpura, actinic purpura, or Bateman purpura, in addition to atrophy of the skin and subcutaneous tissue. These lesions can be painful and a source of morbidity. We report a case of an 80-year-old patient presented for the treatment of dermatoporosis in the upper limbs with polymethylmethacrylate (PMMA) using the BioSculpt®technique. The photographic and ultrasonographic clinical responses of the soft tissue were evaluated before and after nine months of treatment.

Antiulcer mechanisms of the hydroalcoholic extract from Aztec marigolds' medicinal and edible flowers (Tagetes erecta L.).

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.

Effects of different maternal diets on adipose tissue inflammation and liver tissue oxidative stress in dams and their female offspring.

Pregnancy and lactation are important stages of fetal development. Therefore, this study investigated how different maternal diets offered during gestation and lactation periods affect adipose tissue inflammation and liver tissue oxidative stress of dams and their female offspring. Female BALB/c albino mice (60 days old) were randomized into three groups receiving a standard (CONT), hypercaloric (HD), or restricted (RD) diet during the pregnancy. After birth, female offspring weaned at 21 days were divided into two groups that received a standard or restricted diet (CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, and HD/RD) until 100 days old. Histological, oxidative parameters and inflammatory infiltrate of dams' and offspring's liver and adipose tissue were evaluated. HD dams presented non-alcoholic steatohepatitis (NASH) diagnosis and an increase in tumor necrosis factor-alpha (TNF-α) concentrations when compared to the RD and CONT dams, indicating a pro-inflammatory state. High concentrations of malondialdehyde (MDA) formation and catalase (CAT) activity in HD when compared to the CONT in the liver. SOD activity decreased in RD mice compared to CONT, and the SOD/CAT ratio was decreased in the RD and HD in comparison to the CONT. The maternal diet leads to an increase in SOD in RD/RD compared to HD/RD. RD-fed dams showed an increase in inflammatory infiltrates compared to CONT, evidencing changes caused by a restrictive diet. In the HD/CONT offspring, we verified an increase in inflammatory infiltrates in relation to the offspring fed a standard diet. In conclusion, HD, and RD, during pregnancy and lactation, altered the liver and adipose tissues of mothers. Furthermore, the maternal diet negatively impacts the offspring's adipose tissue but does not cause liver damage in these animals in adult life.

Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression.

Introduction: The tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression. Methods: Using in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussion: Neutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1ß, and IL-10 are associated with poor outcomes in patients with GB. Conclusion: These results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.

Viral Coinfection of Children Hospitalized with Severe Acute Respiratory Infections during COVID-19 Pandemic.

The main pathogens of severe respiratory infection in children are respiratory viruses, and the current molecular technology allows for a rapid and simultaneous detection of a wide spectrum of these viral pathogens, facilitating the diagnosis and evaluation of viral coinfection. METHODS: This study was conducted between March 2020 and December 2021. All children admitted to the ICU with a diagnosis of SARI and who were tested by polymerase chain reaction on nasopharyngeal swabs for SARS-CoV-2 and other common respiratory viral pathogens were included in the study. RESULTS: The result of the viral panel identified 446 children, with one infected with a single virus and 160 co-infected with two or more viruses. This study employed descriptive analyses, where a total of twenty-two coinfections among SARI-causing viruses were identified. Thus, the five most frequent coinfections that were selected for the study are: hRV/SARS-CoV-2 (17.91%), hRV/RSV (14.18%), RSV/SARS-CoV-2 (12.69%), hRV/BoV (10.45%), and hRV/AdV (8.21%). The most significant age group was 38.1%, representing patients aged between 24 and 59 months (61 individuals). Patients older than 59 months represented a total of 27.5%, comprising forty-four patients. The use of oxygen therapy was statistically significant in coinfections with Bocavirus, other CoVs, Metapneumovirus, and RSV. Coinfections with SARS-CoV-2 and the other different coinfections presented a similar time of use of oxygen therapy with a value of (p > 0.05). In the year 2020, hRV/BoV was more frequent in relation to other types of coinfections, representing a total of 35.1%. The year 2021 presented a divergent profile, with hRV/SARS-CoV-2 coinfection being the most frequent (30.8%), followed by hRV/RSV (28.2%). Additionally, 25.6% and 15.4% represented coinfections between RSV/SARS-CoV-2 and hRV/AdV, respectively. We saw that two of the patients coinfected with hRV/SARS-CoV-2 died, representing 9.52% of all deaths in the study. In addition, both hRV/hBoV and hRV/RSV had death records for each case, representing 8.33% and 6.67% of all deaths, respectively. CONCLUSION: Coinfections with respiratory viruses, such as RSV and hBoV, can increase the severity of the disease in children with SARI who are admitted to the ICU, and children infected with SARS-CoV-2 have their clinical condition worsened when they have comorbidities.

Natural Products as Modulators of Mitochondrial Dysfunctions Associated with Cardiovascular Diseases: Advances and Opportunities.

The mitochondria have an important role in modulating cell cycle progression, cell survival, and apoptosis. In the adult heart, the cardiac mitochondria have a unique spatial arrangement and occupy nearly one-third the volume of a cardiomyocyte, being highly efficient for converting the products of glucose or fatty acid metabolism into adenosine triphosphate (ATP). In cardiomyocytes, the decline of mitochondrial function reduces ATP generation and increases the production of reactive oxygen species, which generates impaired heart function. This is because mitochondria play a key role in maintaining cytosolic calcium concentration and modulation of muscle contraction, as ATP is required to dissociate actin from myosin. Beyond that, mitochondria have a significant role in cardiomyocyte apoptosis because it is evident that patients who have cardiovascular diseases (CVDs) have increased mitochondrial DNA damage to the heart and aorta. Many studies have shown that natural products have mitochondria-modulating effects in cardiac diseases, determining them as potential candidates for new medicines. This review outlines the leading plant secondary metabolites and natural compounds derived from microorganisms as modulators of mitochondrial dysfunctions associated with CVDs.