RESUMEN

Chronic total occlusion (CTO) percutaneous coronary intervention is a complex procedure and is associated with considerable risk of complications. Several success and complication scores have been developed; however, data regarding their external validation in other populations such as Latin America are scarce. This study aimed to evaluate the accuracy of the main predictors of success and complications in a broad cohort of procedures in the Latin American (LATAM) CTO registry. From April 2008 to December 2023, 3,706 consecutive procedures listed in the LATAM CTO registry were screened. Of these, 2,835 procedures had sufficient information to analyze the Multicenter CTO Registry in Japan (J-CTO); Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS); Ostial location, Rentrop grade, and Age (ORA); Clinical and Lesion-related Score (CL-score); and EuroCTO Score (CASTLE) success scores. The complication scores were PROGRESS (MACE, mortality, and pericardiocentesis) and Outcomes, Patient health status, and Efficiency iN Chronic Total Occlusion hybrid procedures (OPEN-CTO),OPEN-CLEAN. The J-CTO and CASTLE scores demonstrated the highest areas under the curve (AUC) of 0.718 and 0.703, respectively. The AUC value for the CL-score was 0.685, whereas the PROGRESS score had an AUC of 0.598 and the ORA AUC was 0.545. The level of agreement between scores was low; only 4% of the procedures were classified as difficult or very difficult by all scores and <1% were classified as easy by all 5 scores. Of the complication scores, PROGRESS mortality (AUC 0.651) and PROGRESS MACE (AUC 0.588) showed the best performance, identifying groups with >10% event rate. These results may improve the selection of revascularization techniques, especially for patient demographics that are historically underrepresented in CTO research.

Asunto(s)

Oclusión Coronaria , Intervención Coronaria Percutánea , Sistema de Registros , Humanos , Oclusión Coronaria/cirugía , Oclusión Coronaria/diagnóstico , Intervención Coronaria Percutánea/métodos , América Latina/epidemiología , Enfermedad Crónica , Masculino , Femenino , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Estudios Prospectivos

RESUMEN

GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain.

Asunto(s)

Encéfalo , Hormona del Crecimiento , Receptores de Somatotropina , Factor de Transcripción STAT5 , Animales , Factor de Transcripción STAT5/metabolismo , Factor de Transcripción STAT5/genética , Encéfalo/metabolismo , Hormona del Crecimiento/metabolismo , Ratones , Receptores de Somatotropina/metabolismo , Receptores de Somatotropina/genética , Masculino , Ratones Noqueados , Ratones Endogámicos C57BL , Fosforilación , Plexo Coroideo/metabolismo , Hipotálamo/metabolismo , Inyecciones Intraventriculares

RESUMEN

Cardiac function requires appropriate proteins in each chamber. Atria requires slow myosin to act as reservoirs, while ventricles demand fast myosin for swift pumping. Myosins are thus under chamber-biased cis-regulation, with myosin gene expression imbalances leading to congenital heart dysfunction. To identify regulatory inputs leading to cardiac chamber-biased expression, we computationally and molecularly dissected the quail Slow Myosin Heavy Chain III (SMyHC III) promoter that drives preferential expression to the atria. We show that SMyHC III gene states are orchestrated by a complex Nuclear Receptor Element (cNRE) of 32 base pairs. Using transgenesis in zebrafish and mice, we demonstrate that preferential atrial expression is achieved by a combinatorial regulatory input composed of atrial activation motifs and ventricular repression motifs. Using comparative genomics, we show that the cNRE might have emerged from an endogenous viral element through infection of an ancestral host germline, revealing an evolutionary pathway to cardiac chamber-specific expression.

Asunto(s)

Atrios Cardíacos , Pez Cebra , Ratones , Animales , Pez Cebra/genética , Atrios Cardíacos/metabolismo , Ventrículos Cardíacos , Miosinas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo

RESUMEN

Despite success in achieving viral suppression during pregnancy in people living with HIV (PLWH), postpartum adherence remains a challenge. We aimed to describe rates of adherence at a Prevention of Mother-to-Child HIV Transmission (PMTCT) Center before and during the COVID-19 pandemic. This study was conducted from a cohort of PLWH who received prenatal care and were virally suppressed near delivery. We tracked combined antiretroviral therapy (cART) pickups for 12 months and HIV viral load (VL) from 2 to 12 months after delivery. We defined flexible adherence as a monthly pickup of cART and strict adherence as also having VL < 200 copies/mL and at least one maternal HIV VL between two and twelve months postpartum. Pre-pandemic was defined as delivery from March 2017-February 2019 and pandemic as March 2020-February 2022. During the study, 1119 PLWH were followed, and 965 (86%) were suppressed near delivery. There were 511 pre-pandemic and 290 pandemic participants. Adherence rates were 66/511 (13%) and 38/290 (13%), respectively. During the pandemic, more participants conceived using cART and were undetectable at the start of prenatal care; nevertheless, postpartum adherence was no better than pre-pandemic underscoring the need to improve strategies for adherence specific to this subset of PLWH in the postpartum period.

RESUMEN

BACKGROUND: Guide catheter extensions (GCEs) increase support and facilitate equipment delivery, but aggressive instrumentation may be associated with a higher risk of complications. AIM: Our aim was to assess the impact of GCEs on procedural success and complications in patients submitted to chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We analyzed data from the multicenter LATAM CTO Registry. Procedural success was defined as <30% residual stenosis and TIMI 3 distal flow. Major adverse cardiac and cerebrovascular events (MACCE) was defined as the composite of all-cause death, myocardial infarction, target vessel revascularization, and stroke. Propensity score matching (PSM) was used to compare outcomes with and without GCE use. RESULTS: From August 2010 to August 2021, 3049 patients were included. GCEs were used in 438 patients (14.5%). In unadjusted analysis, patients in the GCE group were older and had more comorbidities. The median J-CTO score and its components were higher in the GCE group. After PSM, procedural success was higher with GCE use (87.7% vs. 80.5%, p = 0.007). The incidence of coronary perforation (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.78-2.71, p = 0.230), bleeding (OR: 1.99, 95% CI: 0.41-2.41, p = 0.986), in-hospital death (OR: 1.39, 95% CI: 0.54-3.62, p = 0.495) and MACCE (OR: 1.07, 95% CI: 0.52-2.19, p = 0.850) were similar in both groups. CONCLUSION: In a contemporary, multicenter cohort of patients undergoing CTO PCI, GCEs were used in older patients, with more comorbidities and complex anatomy. After PSM, GCE use was associated with higher procedural success, and similar incidence of adverse outcomes.

Asunto(s)

Oclusión Coronaria , Intervención Coronaria Percutánea , Anciano , Humanos , Catéteres , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/terapia , Oclusión Coronaria/etiología , Mortalidad Hospitalaria , Intervención Coronaria Percutánea/efectos adversos , Resultado del Tratamiento

RESUMEN

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI50 of 10.5 µM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 µM.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Platino (Metal)/farmacología , Platino (Metal)/química , Ligandos , Cisplatino , Antineoplásicos/farmacología , Antineoplásicos/química , Antivirales/farmacología , Paladio/farmacología , Paladio/química , Cristalografía por Rayos X , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Línea Celular Tumoral

RESUMEN

Drug resistance to commercially available antimalarials is a major obstacle in malaria control and elimination, creating the need to find new antiparasitic compounds with novel mechanisms of action. The success of kinase inhibitors for oncological treatments has paved the way for the exploitation of protein kinases as drug targets in various diseases, including malaria. Casein kinases are ubiquitous serine/threonine kinases involved in a wide range of cellular processes such as mitotic checkpoint signaling, DNA damage response, and circadian rhythm. In Plasmodium, it is suggested that these protein kinases are essential for both asexual and sexual blood-stage parasites, reinforcing their potential as targets for multi-stage antimalarials. To identify new putative PfCK2α inhibitors, we utilized an in silico chemogenomic strategy involving virtual screening with docking simulations and quantitative structure-activity relationship predictions. Our investigation resulted in the discovery of a new quinazoline molecule (542), which exhibited potent activity against asexual blood stages and a high selectivity index (>100). Subsequently, we conducted chemical-genetic interaction analysis on yeasts with mutations in casein kinases. Our chemical-genetic interaction results are consistent with the hypothesis that 542 inhibits yeast Cka1, which has a hinge region with high similarity to PfCK2α. This finding is in agreement with our in silico results suggesting that 542 inhibits PfCK2α via hinge region interaction.

Asunto(s)

Antimaláricos , Malaria Falciparum , Malaria , Plasmodium , Antimaláricos/farmacología , Quinasa de la Caseína II/antagonistas & inhibidores , Malaria/tratamiento farmacológico , Malaria/parasitología , Malaria Falciparum/parasitología , Plasmodium/metabolismo , Plasmodium falciparum

RESUMEN

Background: The main challenge of liver transplantation is the discrepancy in demand and availability. Marginal grafts or full organs from donors with expansion criteria have been considered to reduce the shortage and assist a greater number of patients. Nonalcoholic fatty liver disease (NAFLD) is one of the most important defining criteria for expanded criteria organs. The present study proposes that an organized visual analysis method could correctly identify and classify NAFLD and organ viability without the need for liver biopsy and its logistical concerns. Methods: Pictures from the grafts were taken at a standardized method (same distance, light conditions, and register device) before and after the perfusion. The visual liver score (VLS) was applied by transplant surgeons; biopsies of the grafts were analyzed by a pathologist in a double-blind design. Score performance and interobserver agreement for NAFLD detection and grading, as graft viability evaluation, were calculated. Results: Fifty-seven grafts were analyzed. At least 1 previous expansion criterion was presented by 59.64% of donors. The prevalence of NAFLD was 94.73%, with 31.57% borderline nonalcoholic steatohepatitis and 5.26% nonalcoholic steatohepatitis. Steatosis was identified with 48.68% (preperfusion) and 64.03% (postperfusion) accuracy. NAFLD stratification was performed with 49.53% (preperfusion) and 46.29% (postperfusion) accuracy. Viability related to NAFLD was identified with 51.96% (preperfusion) and 48.52% (postperfusion) accuracy. Interobserver agreement was moderate for total VLS and poor for individual components of VLS. Conclusions: Although a standardized method was not reliable enough for visual evaluation of NALFD compared with pathology, efforts should be made to expand access to biopsy. Further studies are needed to understand whether the VLS needs to be adapted or even excluded in the liver transplant scenario, to assess the importance of ectoscopy related to posttransplant clinical outcomes, and to determine its role in graft selection.

RESUMEN

A lack of control over blood loss can have catastrophic implications, including death. Although several hemostatic medications have been employed to reduce bleeding, a vast majority of them are ineffective, expensive, or pose health risks to the patient. To overcome these constraints, chitosan-polyethylene glycol (CS-PEG) hemostatic gels loaded with ethanolic extract of Jatropha mollissima sap (EES) were prepared and their hemostatic, physicochemical, and cytotoxic properties were evaluated. The gels were produced by mixing CS with PEG (an external plasticizer) and EES. The phytochemical analysis revealed a significant concentration of total polyphenols and tannins content in the extract and catechin was identified as one of the key compounds of EES. Infrared spectroscopy analysis revealed the presence of EES in the gels, as well as the chemical interaction between CS and PEG. The gels were thermally stable between 25 and 37 °C (ambient and human body temperature range), had pseudoplastic deformation behavior (rheological properties preserved after shearing), were simple to inject (compression force 30 N), and were biocompatible. In vivo experiments showed that both CS-PEG-EES gels exhibited greater hemostatic action in preventing tail hemorrhage in Wistar rats, with decreased bleeding time and blood weight compared with unloaded CS-PEG gels (control groups) and Hemostank, a commercial product. However, the gel prepared with acetic acid was more efficient in controlling bleeding. These findings reveal that CS-PEG-EES gels can reduce hemorrhages and are a potent, simple, and safe hemostatic agent.

RESUMEN

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Asunto(s)

COVID-19 , Fuerza de la Mano , Adulto , Humanos , Persona de Mediana Edad , Presión Sanguínea/fisiología , Hemodinámica , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Simpático , Antebrazo/irrigación sanguínea , Músculo Esquelético/inervación

RESUMEN

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS.

RESUMEN

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

Asunto(s)

Síndrome Coronario Agudo , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Clorhidrato de Prasugrel/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Quimioterapia Combinada , Aspirina/uso terapéutico , Hemorragia/inducido químicamente , Resultado del Tratamiento

RESUMEN

PURPOSE: Although liver transplantation (LT) outcomes have improved significantly over the last decades, early vascular complications are still associated with elevated risks of graft failure. Doppler ultrasound (DUS) enables detection of vascular complications, provides hepatic artery Resistive Index (RI). The aim of our study was to evaluate the association of the RI parameters of DUS performed in the first post-transplant week with post-transplant outcomes. METHODS: All consecutive patients undergoing a first LT between 2001 and 2019 at a single center were included. Patients were divided into two groups: RI < 0.55 and RI ≥ 0.55. Patients were also divided according to the presence or absence of hepatic artery thrombosis (HAT). Graft survival was compared between groups. RESULTS: Overall, 338 patients were included. HAT occurred in 23 patients (6.8%), of which 7 were partial and 16, complete. Biliary complications were more common in patients with HAT (10 [43.5%]) vs. 38 [12.1%] [p < 0.001]). Graft survival was lower for patients with HAT (p = 0.047). Also, RI < 0.55 was associated with increased incidence of HAT (p < 0.001). Additionally, patients with RI < 0.55 on post-operative day 1 had decreased graft survival as compared to patients with RI > 0.55 (p = 0.041). RI on post-operative day 3 and 5 was not predictive of inferior graft outcomes. CONCLUSIONS: Intensive use of DUS in the early post-LT period offers the possibility of early diagnosis of vascular complications, guiding medical and surgical management of HAT. Additionally, according to our data, low RI (< 0.55) on the first postoperative day also is a predictor of HAT and decreased graft-survival.

Asunto(s)

Trasplante de Hígado , Trombosis , Humanos , Arteria Hepática , Supervivencia de Injerto , Ultrasonografía Doppler

RESUMEN

Large gaps in reef distribution may hinder the dispersal of marine organisms, interrupting processes vital to the maintenance of biodiversity. Here we show the presence and location of extensive reef habitats on the continental shelf between the Amazon Reef System (ARS) and the Eastern Brazilian Reef System (ERS), two reef complexes off eastern South America. Formations located 20-50 m deep include both biogenic and geogenic structures. The presence of diverse reef assemblages suggests the widespread occurrence of rocky substrates below 50 m. These habitats represent an expansion of both the ARS and ERS and the closure of the only remaining large-scale gap (~ 1000 km) among West Atlantic reef environments. This indicates that the SW Atlantic harbors a single, yet heterogeneous, reef system that stretches for about 4000 km, and thus, represents one of the largest semi-continuous tropical marine ecosystems in the world.

Asunto(s)

Biodiversidad , Ecosistema , Animales , Organismos Acuáticos , Brasil , Arrecifes de Coral , Peces

RESUMEN

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by progressive dopaminergic neuron loss. Animal models have been used to develop a better understanding of the pathophysiologic mechanisms of PD. However, these models are usually conducted with young animals diverging of the age of PD patients, suggesting a bias in translational science. Thus, the aim of the study was to evaluate the effect of the age on rats in a progressive parkinsonism model induced by reserpine (RES). Adult (6 - 8 month-old) or elderly (18 - 24 month-old) male rats were assigned to six groups: control-elderly (CTL-ELDERLY), reserpine-elderly (RES-ELDERLY), reserpine-elderly withdrawal (RES-ELDERLY WITHDRAWAL), control-adult (CTL-ADULT), reserpine-adult (RES-ADULT), and reserpine-adult withdrawal (RES-ADULT WITHDRAWAL). Animals received 15 injections every other day of RES (0.1 mg / kg) or vehicle during 30 days. Throughout treatment, animals were evaluated in the catalepsy test (every 48 h) and open field test (24 h after the second injection), and weight assessment (every 4 days) was also made. Upon completion of behavioral tests, rat brains were collected for tyrosine hydroxylase (TH) immunohistochemical analysis. Main results demonstrated that RES-treated animals spent more time in the catalepsy bar compared with control groups, moreover the RES-elderly group showed a longer catalepsy time compared with the RES-ADULT group. A shorter time from RES treatment to the development of symptoms was observed in the RES-ADULT group, compared with the RES-ELDERLY group. In addition, RES-induced weight loss in both RES-ELDERLY and RES-ADULT when compared with their corresponding controls. Cessation of RES treatment was followed by weight gain only in the RES-ADULT group. A significant decrease in TH-immunoreactive cells was observed in the substantia nigra pars compacta (SNpc) and dorsal striatum (STR) in the rats in both the RES-ADULT and RES-ELDERLY groups and in the ventral tegmental area in rats in the RES-ADULT group. Furthermore, TH immunoreactivity decrease was not reversible in SNpc and STR in the RES-ELDERLY. These results show that RES has an age-dependent effect in rats, suggesting a greater sensitivity of the dopaminergic pathway to RES with advancing age. These suggest that the RES rat model of parkinsonism can be useful in improving our knowledge on the effect of aging on neurodegeneration.

Asunto(s)

Trastornos Motores , Enfermedad de Parkinson , Trastornos Parkinsonianos , Animales , Masculino , Ratas , Tirosina 3-Monooxigenasa/metabolismo , Reserpina/toxicidad , Catalepsia , Actividad Motora , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/metabolismo , Dopamina/metabolismo , Envejecimiento , Sustancia Negra/metabolismo , Modelos Animales de Enfermedad

RESUMEN

Aims: Both postprandial lipemia (PPL) and disturbed blood flow (DBF) induce endothelial dysfunction. However, the interactive effect of these stimuli on endothelial function is currently unknown. In the present study, we tested whether PPL plus DBF causes a greater reduction in flow-mediated dilation (FMD) than PPL and if this response is associated with elevations in oxidative stress and endothelial microvesicles (EMVs). Methods: Eighteen individuals (aged 28 ± 1yrs, 3 females, and BMI 24.43 ± 0.8kg/m2) randomly underwent two experimental sessions: PPL and PPL plus DBF. FMD and venous blood samples were obtained at baseline and 30, 70, and 110 min after stimulation. PPL was induced by fat overload via mozzarella pizza ingestion and DBF by forearm cuff inflation to 75 mm Hg per 30 min. Lipidic profile, oxidative stress (thiobarbituric acid reactive substances, TBARS; ferric reducing/antioxidant power, FRAP; hydrogen peroxide, H2O2) and EMVs were measured in blood samples. Results: Hypertriglyceridemia was observed in both sessions. Retrograde shear rate and oscillatory index responses were significantly higher in the PPL plus DBF compared with PPL. PPL plus DBF evoked a greater reduction in FMD than did PPL and EMVs, NADPH oxidase, and H2O2 similarly increased in both sessions, but TBARS and FRAP did not change. Conclusion: These data indicate that the association of PPL plus DBF additively impairs endothelium-dependent function in 110 min after stimulus in healthy individuals, despite a similar increase in oxidative stress and EMVs. Further studies are needed to understand the mechanisms associated with the induced-endothelial dysfunction by association of PPL and DBF.

RESUMEN

Believed to cause damage to the nervous system and possibly being associated with neurodegenerative diseases, deltamethrin (DM) is a type II pyrethroid used in pest control, public health, home environment, and vector control. The objective of this study was to evaluate the motor, cognitive and emotional changes associated with dopaminergic and BDNF imbalance after DM exposure in rats. Sixty Wistar rats (9-10 months-old) were used, under Ethics Committee on Animal Research license (ID 19/2017). The animals were randomly divided into four groups: control (CTL, 0.9% saline), DM2 (2 mg DM in 1.6 mL 0.9% saline), DM4 (4 mg of DM in 1.6 mL of 0.9% saline), and DM8 (8 mg of DM in 1.6 mL of 0.9% saline). DM groups were submitted to 9 or 15 inhalations, one every 48 h. Half of the animals from each group were randomly selected and perfused 24 h after the 9th or 15th inhalation. Throughout the experiment, the animal's behavior were evaluated using catalepsy test, open field, hole-board test, Modified Elevated Plus Maze, and social interaction. At the end of the experiments, the rats were perfused transcardially and their brains were processed for Tyrosine Hydroxylase (TH) and Brain derived neurotrophic factor (BDNF) immunohistochemistries. The animals submitted to 9 inhalations of DM showed a reduction in immunoreactivity for TH in the Substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and dorsal striatum (DS) areas, and an increase in BDNF in the DS and CA1, CA3 and dentate gyrus (DG) hippocampal areas. Conversely, the animals submitted to 15 inhalations of DM showed immunoreactivity reduced for TH in the SNpc and VTA, and an increase in BDNF in the hippocampal areas (CA3 and DG). Our results indicate that the DM inhalation at different periods induce motor and cognitive impairments in rats. Such alterations were accompanied by dopaminergic system damage and a possible dysfunction on synaptic plasticity.

Asunto(s)

Ansiedad/inducido químicamente , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Encéfalo/efectos de los fármacos , Disfunción Cognitiva/inducido químicamente , Insecticidas/farmacología , Trastornos de la Memoria/inducido químicamente , Actividad Motora/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Nitrilos/farmacología , Piretrinas/farmacología , Tirosina 3-Monooxigenasa/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Dopamina/metabolismo , Exposición por Inhalación , Insecticidas/administración & dosificación , Nitrilos/administración & dosificación , Piretrinas/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Wistar , Conducta Social

RESUMEN

This study evaluated the ability of resistance training (RT) of moderate intensity to promote vascular changes in insulin-induced vasodilation in healthy animals. Wistar rats were divided into two groups: control (CON) and trained (eight weeks of training, performing 3 sets with 10 repetitions at 60% of maximum intensity). Forty-eight hours after the last session of the RT, the animals were sacrificed and vascular reactivity to insulin in the absence and presence of LY294002 (phosphatidylinositol 3-kinase inhibitors (PI3K), L-NAME (nitric oxide synthase (NOS) inhibitors) and BQ123 (endothelin A antagonist (ET-A) receptor). In addition, phenylephrine (Phe)-induced vasoconstriction in the absence and presence of L-NAME was also evaluated. The RT group showed greater vasodilation in maximal response compared to the CON group. After PI3K inhibition, vasodilation was reduced in both groups. However, when the NOS participation was evaluated, the RT group showed contraction in relation to the CON group, which was abolished by BQ123. In addition, the RT group had an increase in nitrite levels compared to the CON group. When the Phe response was evaluated, there was a reduction in tension in the RT group compared to the CON group. The results suggest that RT improves vascular reactivity.

Asunto(s)

Entrenamiento de Fuerza , Vasodilatación , Animales , Humanos , Insulina , Arterias Mesentéricas , Óxido Nítrico , Fosfatidilinositol 3-Quinasas , Inhibidores de las Quinasa Fosfoinosítidos-3 , Ratas , Ratas Wistar

RESUMEN

Human BMP-2, a homodimeric protein that belongs to the TGF- ß family, is a recognized osteoinductor due to its capacity of inducing bone regeneration and ectopic bone formation. The administration of its recombinant form is an alternative to autologous bone grafting. A variety of E. coli-derived hBMP-2 has been synthesized through refolding of cytoplasmic inclusion bodies. The present work reports the synthesis, purification, and characterization of periplasmic hBMP-2, obtained directly in its correctly folded and authentic form, i.e., without the initial methionine typical of the cytoplasmic product that can induce undesired immunoreactivity. A bacterial expression vector was constructed including the DsbA signal peptide and the cDNA of hBMP-2. The periplasmic fluid was extracted by osmotic shock and analyzed via SDS-PAGE, Western blotting, and reversed-phase high-performance liquid chromatography (RP-HPLC). The purification was carried out by heparin affinity chromatography, followed by high-performance size-exclusion chromatography (HPSEC). HPSEC was used for qualitative and quantitative analysis of the final product, which showed >95% purity. The classical in vitro bioassay based on the induction of alkaline phosphatase activity in myoblastic murine C2C12 cells and the in vivo bioassay consisting of treating calvarial critical-size defects in rats confirmed its bioactivity, which matched the analogous literature data for hBMP-2.

Asunto(s)

Proteína Morfogenética Ósea 2/biosíntesis , Escherichia coli/metabolismo , Periplasma/metabolismo , Animales , Bioensayo , Reactores Biológicos , Línea Celular , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Fermentación , Humanos , Masculino , Ratones , Osteogénesis , Ratas Wistar , Cráneo/patología

RESUMEN

Abstract We describe one case of iatrogenic rupture of the left ventricle after mitral valve replacement and myectomy of the outflow tract. The cause and site of the rupture could not be identified, neither from the internal nor from the external examination. After unsuccessful use of hemostatic patches in the surface of the ruptured area, wrapping of the ventricles with a surgical gauze pad controlled the hemorrhage, hence saving the patient's life.

Asunto(s)

Humanos , Ventrículos Cardíacos/cirugía , Válvula Mitral/cirugía