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1.
Eur J Health Econ ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026155

RESUMO

OBJECTIVES: A centralised approach to health technology assessment (HTA) may facilitate optimal use of HTA resources. A regional approach may increase the chances of local implementation of recommendations. This study aimed to compare assessment procedures in England (centralised HTA approach) with Spain (regional HTA approach) discussing key challenges and opportunities from both approaches. METHODS: We compared technology assessments of anticancer medicines in the two jurisdictions from 2008 to 2015. To assess the implementation of HTA recommendations, we assessed trends in medicine usage using regression methods. We used IQVIA data, from 2011 to 2016, for a sample of 11 medicines. We used CatSalut data from Catalonia to assess the implementation of local recommendations. RESULTS: In England, 66 assessments were undertaken by the National Institute for Health and Care Excellence (NICE), using a standardised methodology. In Spain, there were 79 reports undertaken by a range of bodies using a shared process and coordinated through the GENESIS collaboration; the assessment methods used varied substantially. Overall, the recommendations in the two jurisdictions were similar. Regression analyses indicate that where there is a positive recommendation by HTA bodies, the usage of the medicine responds most strongly (p < 0.001) in Catalonia (4.892), followed by England (3.120) and Spain (1.693). CONCLUSIONS: This study suggests that medicine utilisation does respond to the positive recommendations of HTA bodies. However, if HTA capacity is organised primarily regionally, considerable effort may be required in coordination, to ensure consistent and rigorous assessments and adequate implementation of HTA findings.

2.
Reprod Fertil Dev ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32087765

RESUMO

Ovary fragments from six sexually mature cats were vitrified in the presence or absence of betaine or ascorbic acid, loaded (7.4 or 74µM betaine; 20 or 200µM ascorbic acid) or not (1mM betaine or 0.3mM ascorbic acid) into CaCO3 microparticles, and assessed for follicular morphology, oxidative stress and mitochondrial activity Feline ovarian tissue was successfully preserved after vitrification in the presence of 74µM betaine loaded in CaCO3 microparticles, as confirmed by morphological analysis and the density of preantral follicles and stromal cells, as well as by the increased mitochondrial activity and decreased production of reactive oxygen species.

4.
J Ethnopharmacol ; 251: 112571, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935494

RESUMO

BACKGROUND: Senecio biafrae is a medicinal plant widely used in traditional medicine to cure female infertility. Some effects have been pharmacologically demonstrated on immature female rats but in vivo and in vitro investigations are still necessary for determining its mechanism of action. The aim of the present study was to evaluate the estrogenic and FSH-like effects of the plant extracts and fractions on some fertility parameters in immature female rats and on in vitro survival and growth of swine preantral follicles. METHODS: 21-23 days old female Wistar rats orally received extracts and fractions of S. biafrae at 0, 8 and 64 mg/kg doses over 20 days. The LH, FSH, estradiol and progesterone serum levels were evaluated as well as the ovarian cholesterol, uterus and ovaries masses and proteins. The numbers of follicles at different developmental stages were recorded in ovarian cortexes after histology. Slices of swine ovarian cortexes were cultured along 1 or 7 days in alpha-minimum essential medium (α-MEM) and fixed for morphological analysis of preantral follicles. The fresh control, cultured control (CIV control) and different Senecio biafrae-treated ovarian fragments were analyzed for preantral follicles development. Treatments that showed the best follicle growth in culture were submitted to AgNOR test. The aqueous and MeOH/CH2Cl2 extracts as well as the ethyl acetate and hexane fractions of S. biafrae were submitted to the HPLC for analysis of polyphenolic secondary metabolites. RESULTS: Ovarian and uterine proteins were significantly high (p < 0.01) in animals treated with the two dosages of ethyl acetate and n-butanol fractions. The same result was recorded with uterine proteins in animals treated with the hexane fraction. The FSH level significantly dropped with all ethanolic extract doses and with the 64 mg/kg dosage of the methanol/methylene chloride (MeOH/CH2Cl2) extract while LH was reduced (p < 0.01) in almost all the treated groups. Estradiol level was significantly increased (p < 0.001) in the three groups receiving the extracts, but reduced (p < 0.001) in the three groups receiving the fractions of the plant. The progesterone level increased with almost all the treated groups. Primary and secondary follicles augmented (p < 0.01) in MeOH/CH2Cl2 extract and n-butanol fraction while tertiary follicles increased with the same extract and the ethyl acetate fraction (p < 0.05). Treatments with aqueous and ethanolic extracts as well as ethyl acetate fraction led to a significant increase (p < 0.05) in the number of morphologically normal follicles after 7 days of culture as compared to the CIV control. The number of AgNOR dots per follicle was significantly low (p < 0.05) in all cultured groups as compared to the fresh control, except the ethyl acetate 2.8 ng/ml dosage. The same observation was done with AgNOR dots per cell in the 2.8 ng/ml dosage aqueous extract-treated fragments. The phenolic compounds mainly encountered in the plant, independently of the extract or fraction are apigenin, eugenol and rutin. CONCLUSION: Extracts and fractions of S. biafrae have an important FSH-like effect which induces follicular survival and growth.

5.
J Int Soc Sports Nutr ; 17(1): 3, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906976

RESUMO

BACKGROUND: Rating of Perceived Exertion (RPE) is a subjective scale to monitor overload and fatigue during exercise. Hypoxia may worsen the perception of fatigue, compromising the self-reported perception of effort and increasing RPE. The objective was to evaluate the effects of carbohydrate (CHO) supplementation on RPE during exercise in hypoxia simulating 4200 m. METHODS: Eight male physically active volunteers performed two exercises at 50% VO2peak and 1% slope: exercise in hypoxia + placebo or exercise in hypoxia + CHO (6% maltodextrin) with supplementation at 20, 40, and 60 min during exercise. Oxygen Saturation (SaO2%) was assessed at baseline and after exercise, while RPE and HR were measured each 10 min during the trial. RESULTS: SaO2% decreased after exercise in both conditions of hypoxia compared to rest. The RPE did not differ between groups. However, the RPE increased in hypoxia after 20 min of exercise in relation to 10 min. The Area Under the Curve (AUC) of RPE was lower in hypoxia + CHO compared to hypoxia. The AUC of the HR/RPE ratio in the hypoxia + CHO group was higher in relation to hypoxia. CONCLUSIONS: Our results indicate that CHO supplementation does not change RPE induced by 60 min of exercise at 50% VO2peak in hypoxia equivalent to 4200 m at the different times analyzed. However, in hypoxia + CHO the (AUC)-60 min of total RPE decreased during exercise, while the heart rate/RPE ratio improved, indicating lower RPE in the hypoxic environment.

7.
Histochem Cell Biol ; 153(1): 63-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654127

RESUMO

The genre Mycobacterium includes a series of pathological species, such as M. tuberculosis, which is important for pathology laboratories to detect for a correct diagnosis. The Ziehl-Neelsen technique (ZNT) is the most commonly histochemical method used to detect these bacilli and uses a heated mixture of carbol-fuchsine, which contains basic fuchsine and phenol. Whereas the former component is responsible for the pinkish staining of acid-fast mycobacteria, the role of phenol is not completely understood and it has been suggested that its exclusion does not impact the detection ability of the ZNT. Since phenol is highly toxic and induces several injuries, the goal of this study is to determine the detection capacity of mycobacteria through a method that excludes the use of phenol. Accordingly, the GASMoC method, a modified ZNT that employs a solution of aqueous basic fuchsine heated at 37 °C, was tested on histological samples positive for mycobacteria and the results were compared to that of the ZNT. Data demonstrated that the GASMoC method was able to detect acid-fast bacilli (AFB) in all analyzed cases. Remarkably, microscopic inspection of mycobacteria was easier when the GASMoC method was applied. In conclusion, our study demonstrates that AFB detection does not require phenol and that the GASMoC method, a phenol-free technique, may substitute the ZNT in pathology laboratories.

8.
Animal ; 14(1): 86-94, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31416494

RESUMO

With still limited information on vitamin requirements and considering that many commercial practices adopt dietary vitamin levels above the values suggested by nutritional tables, this study aimed to assess the effect of administering vitamin supplementation to sows in gestation and lactation and to their litters on the reproductive performance and body condition of the sows and on the performance and immune profile of the litters until slaughter. The trial was split into two phases. The first phase used 104 sows, assigned to be randomized to blocks according to parity, submitted until 21 days of lactation to two treatments: control-standard (standard levels of vitamins) and test-elevated (elevated levels of vitamins). Each sow and its respective farrow were considered an experimental unit. The sows underwent evaluations of body condition score, back fat thickness and reproductive performance. In the second phase, 60 barrows and 60 gilts at 21 days of age and mean initial weight of 5.33 ± 1.5 kg until slaughter at 164 days of age. The piglets were assigned to randomized blocks according to the weight and sex of the animals in a 2 × 2 factorial model, with 10 replicates per treatment, where a pen with three animals represented the experimental unit. Following the same treatments of the first phase, the piglets were evaluated for daily weight gain, daily feed intake, feed conversion, mortality rate and humoral immune response. Vitamin supplementation had no positive effects on the reproductive parameters or body composition of sows. However, it positively impacted the performance of the litters in the early nursery stage, but did not lead to superior effects on the immune responses to vaccination against circovirus or mycoplasma.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31802248

RESUMO

Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck's personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01-1.06; and OR, 1.03; 95%CI 1.01-1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11-1.26), personal psychiatric history (OR 2.1; 95%CI 1.33-3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12-3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.

10.
Neotrop Entomol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802413

RESUMO

Anastrepha obliqua (Macquart) is an agricultural pest of wide geographic distribution infesting a vast list of host species in America. However, little is known about the past geographic distribution of this species. In this study, we investigated the potential past and current distribution of species in South America. In this sense, the MaxEnt algorithm was used to model the ecological niche of the species in the past (Last Interglcial Maximum; Last Glacial Maximum) and current periods. The results suggested that under the current climatic conditions, A. obliqua showed high environmental suitability to become established in most South American countries, especially in Brazil. The lowest suitability indices were observed in Chile, Argentina, and Uruguay. The past analysis for Last Glacial Maximum revealed that there was no significant change in the distribution potential of the species when compared to the current model; however, in the Last Interglacial Maximum period, there was a large reduction in the areas of suitability for the species when compared to the current and Last Glacial Maximum distribution models. The analysis also revealed vast areas of refuges for the species mainly on the coast of Brazil, as well as Venezuela, Bolivia, Guyana, and Surinam. The results presented here may be useful for future phylogeographical studies in order to test if the refuge areas concentrate greater genetic diversity for this species. In addition, our study provides important information for understanding the current dynamics of A. obliqua, which may be useful for control programs in places where this species can become a pest.

11.
J Med Case Rep ; 13(1): 387, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31884973

RESUMO

BACKGROUND: Chest pain associated with transient electrocardiogram changes mimicking an acute myocardial infarction have been described in acute pancreatitis. These ischemic electrocardiogram changes can present a diagnostic dilemma, especially when patients present with concurrent angina pectoris and epigastric pain warranting noninvasive or invasive imaging studies. CASE PRESENTATION: A 45-year-old African-American man with a history of alcohol use disorder presented to the emergency department of our institution with 36 hours of concurrent epigastric pain and left-sided chest pain radiating to his left arm and associated with nausea and dyspnea. On physical examination, he was afebrile; his blood pressure was elevated; and he had epigastric tenderness. His laboratory test results were significant for hypokalemia, normal troponin, and elevated serum lipase and amylase levels. Serial electrocardiograms for persistent chest pain showed ST-segment elevations with dynamic T-wave changes in the right precordial electrocardiogram leads, consistent with Wellens syndrome. He was immediately taken to the cardiac catheterization laboratory, where selective coronary angiography showed normal coronary arteries with an anomalous origin of the right coronary artery from the opposite sinus. Given his elevated lipase and amylase levels, the patient was treated for acute alcohol-induced pancreatitis with intravenous fluids and pain control. His chest pain and ischemic electrocardiogram changes resolved within 24 hours of admission, and coronary computed tomography angiography showed an interarterial course of the right coronary artery without high-risk features. CONCLUSIONS: Clinicians may consider deferring immediate cardiac catheterization and attribute electrocardiogram changes to acute pancreatitis in patients presenting with angina pectoris and acute pancreatitis if confirmed by normal cardiac enzymes and elevated levels of lipase and amylase. However, when clinical signs and electrocardiogram findings are highly suggestive of myocardial ischemia/injury, immediate noninvasive coronary computed tomography angiography may be the best approach to make an early diagnosis.

12.
Braz J Med Biol Res ; 52(11): e8441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721904

RESUMO

The heptapeptide Bj-PRO-7a, isolated and identified from Bothrops jararaca (Bj) venom, produces antihypertensive and other cardiovascular effects that are independent on angiotensin converting enzyme inhibition, possibly relying on cholinergic muscarinic receptors subtype 1 (M1R). However, whether Bj-PRO-7a acts upon the central nervous system and modifies behavior is yet to be determined. Therefore, the aims of this study were: i) to assess the effects of acute administration of Bj-PRO-7a upon behavior; ii) to reveal mechanisms involved in the effects of Bj-PRO-7a upon locomotion/exploration, anxiety, and depression-like behaviors. For this purpose, adult male Wistar (WT, wild type) and spontaneous hypertensive rats (SHR) received intraperitoneal injections of vehicle (0.9% NaCl), diazepam (2 mg/kg), imipramine (15 mg/kg), Bj-PRO-7a (71, 213 or 426 nmol/kg), pirenzepine (852 nmol/kg), α-methyl-DL-tyrosine (200 mg/kg), or chlorpromazine (2 mg/kg), and underwent elevated plus maze, open field, and forced swimming tests. The heptapeptide promoted anxiolytic and antidepressant-like effects and increased locomotion/exploration. These effects of Bj-PRO-7a seem to be dependent on M1R activation and dopaminergic receptors and rely on catecholaminergic pathways.


Assuntos
Ansiedade , Comportamento Animal/efeitos dos fármacos , Venenos de Crotalídeos/química , Depressão , Comportamento Exploratório/efeitos dos fármacos , Oligopeptídeos/farmacologia , Prolina/farmacologia , Animais , Comportamento Animal/fisiologia , Masculino , Oligopeptídeos/isolamento & purificação , Prolina/isolamento & purificação , Ratos , Ratos Wistar
13.
Mar Environ Res ; : 104810, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31733909

RESUMO

Seagrasses often occur around shallow marine CO2 seeps, allowing assessment of trace metal accumulation. Here, we measured Cd, Cu, Hg, Ni, Pb and Zn levels at six CO2 seeps and six reference sites in the Mediterranean. Some seep sediments had elevated metal concentrations; an extreme example was Cd which was 43x more concentrated at a seep site than its corresponding reference site. Three seeps had metal levels that were predicted to adversely affect marine biota, namely Vulcano (for Hg), Ischia (for Cu) and Paleochori (for Cd and Ni). There were higher-than-sediment levels of Zn and Ni in Posidonia oceanica and of Zn in Cymodocea nodosa, particularly in roots. High levels of Cu were found in Ischia seep sediments, yet seagrass was abundant there, and the plants contained low levels of Cu. Differences in bioavailability and toxicity of trace elements helps explain why seagrasses can be abundant at some CO2 seeps but not at others.

14.
FEMS Microbiol Ecol ; 95(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730173

RESUMO

Archaea have been the most overlooked and enigmatic of the three domains of life for decades. Knowledge of key ecological interactions, such as trophic links between this domain and higher level organisms, remains extremely limited. The co-occurrence of halophilic Archaea (haloarchaea) and the non-selective filter feeder, brine shrimp Artemia under the unique ecological characteristics of hypersaline aquatic environments, constitutes an excellent opportunity to further unravel the ecological role of the Archaea domain as a source of food to zooplankton metazoans. In the present study, we combine the use of haloarchaea biomass assimilation experiments using 13C isotope as tracer, with gnotobiotic Artemia culture tests using haloarchaea mono-diets, to investigate potential trophic links between the organisms. Our results demonstrated the ability of Artemia to assimilate nutrients from mono-diets of haloarchaea biomass in order to survive and grow, providing clear indications that archivory may occur in hypersaline aquatic environments. Additionally, our study highlights the use of stable isotopes labelling as a potential tool to further disentangle the specific pathways by which archaeal cellular constituents are digested by consumers.

15.
Arch Pediatr ; 26(7): 431-436, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31611144

RESUMO

Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance. OBJECTIVE: The aim of this work was to evaluate the organoleptic excipients in oral antibiotics for pediatric use marketed in Brazil. METHODS: The information was obtained from the GuidetoPharmacy, a reference for the pharmaceutical trade. The analysis included dosage forms for oral administration and drugs and their combination with antibacterial action. After this survey, we identified the constitution of the flavoring, sweetening, and coloring agents of each medicine. The results are presented in a descriptive form. RESULTS: Twelve drugs or associations are distributed in 70medicines. Oral suspension was the most common pharmaceutical dosage form. Sweeteners were sucrose, sodium saccharin, and sodium cyclamate. All the coloring agents observed are synthetic and the most frequent ones were yellow twilight no. 6, yellow tartrazine no. 5, and red ponceau 4R. The presence of two or more types of flavorings per medicine was observed. CONCLUSION: Antibacterials use coloring agents, flavorings, and sweeteners to facilitate the administration of medicines for children, using up to six different substances per formulation. No natural coloring agent was observed, demonstrating an issue to be explored in the future. It is important to note that, although necessary, these excipients are responsible for a high incidence of allergic reactions in children.

16.
J Comp Pathol ; 171: 6-11, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31540627

RESUMO

Canine visceral leishmaniosis (CVL) is an important zoonotic disease, which is endemic in Brazil and several other parts of the world. The disease may affect multiple organs, but lesions in the oral cavity are considered uncommon. Twenty-three cases of oral lesions compatible with CVL were diagnosed from 2015 to 2018 in the Federal District, Brazil. Six cases were confirmed to be CVL based on histopathology, immunohistochemistry and polymerase chain reaction amplification of Leishmania infantum kDNA. Most of the affected dogs were >9 years of age, of mixed breed and were classified as having stage C of the disease. The most important gross findings were ulcerated nodular lesions in the tongue, lip, gingiva and hard palate. Microscopically, there was lymphoplasmacytic to granulomatous inflammation that was diffuse, moderate to severe and associated with ulceration. CVL should be considered in the differential diagnosis of nodular and ulcerative oral lesions in dogs.

17.
J Food Sci ; 84(10): 2955-2960, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31509251

RESUMO

This study aimed to identify consumers' preferences and impressions of minimally processed "Gala" cultivar apples, using preference tests and word associations. The study was conducted online via the Google Docs tool and sent out via social networks. The participants were 607 individuals, mostly women, mainly between the ages of 18 and 45, with education up to undergraduate and postgraduate level. As regards the preference for minimally processed apples, the profile of the consumer did not influence the choice. The profiles analyzed were gender and education. For the word association test, 11-word categories were formed, and among these, the most important aspect was appearance, followed by taste and texture, which was confirmed by correspondence analysis. Sample A (0 days-no storage) was the most preferred one, differing significantly from the other samples, whereas sample B (3 days of storage) and sample C (6 days of storage) were associated with characteristics for choice of product. The word association methodology revealed the consumer's impressions of the product, in addition to demonstrating simplicity, low cost, speed, and an exploratory character. PRACTICAL APPLICATION: Gender and level of schooling did not influence the choice of minimally processed apples. Appearance was the most cited word in the word association test. Word association is a simple, fast, inexpensive, and projective technique.


Assuntos
Comportamento do Consumidor , Malus/química , Adolescente , Adulto , Comportamento de Escolha , Feminino , Manipulação de Alimentos , Frutas/química , Humanos , Masculino , Pessoa de Meia-Idade , Paladar , Adulto Jovem
18.
Exp Physiol ; 104(12): 1754-1761, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31553087

RESUMO

NEW FINDINGS: What is the central question of this study? Can Na+ depletion mobilize Na+ from the skin reservoir in ovariectomized rats? Does oestrogen replacement change the amount and the dynamics of skin Na+ storage? Is the reduced salt appetite after Na+ depletion in ovariectomized rats with oestrogen replacement related to changes in the skin Na+ ? What is the main finding and its importance? This work demonstrated that acute body Na+ depletion induced by frusemide mobilized the osmotically inactive skin Na+ reservoir to become osmotically active. Oestrogen treatment decreased the induced Na+ intake in ovariectomized rats but did not modulate the inactive Na+ reservoir in control conditions or its mobilization induced by Na+ depletion. ABSTRACT: Oestradiol, which is an important hormone for water and electrolyte balance, also has a role in the inhibition of induced Na+ appetite. Sodium can be stored in the skin in osmotically active or inactive forms, and this skin Na+ reservoir may be involved in the control of body Na+ levels during physiopathological challenges. In this study, we investigated whether the effect of sodium depletion by frusemide can mobilize Na+ from the skin reservoir and whether oestradiol replacement changes or mobilizes the Na+ reserves in the skin. Ovariectomized Wistar rats were treated with vehicle or oestradiol for 7 days to evaluate the effects of oestrogen on the hydroelectrolyte balance, intake responses and skin Na+ and water content in basal conditions. Furthermore, the effects of oestrogen were evaluated after 24 h frusemide-induced whole-body Na+ depletion. Oestradiol-replaced rats exhibited reduced water intake without any significant changes in salt intake, Na+ excretion or water and Na+ skin content in basal conditions. After sodium depletion, both vehicle- and oestradiol-treated rats exhibited an increase in the osmotically active skin Na+ , which was associated with a decrease of the inactive skin Na+ reservoir. Oestrogen decreased the hypertonic saline intake induced by Na+ depletion, but it was not associated with any significant changes in the skin Na+ reservoir. Thus, sodium depletion is able to change the inactive-active skin Na+ reservoir balance. However, the oestrogenic modulation of sodium appetite after Na+ depletion is probably not related to the action of this hormone in the skin Na+ reservoir balance.

19.
Rev Neurol (Paris) ; 175(10): 604-613, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31519304

RESUMO

A growing number of studies have shown that exposure to air pollutants such as particulate matter and gases can cause cardiovascular, neurodegenerative and psychiatric diseases. The severity of the changes depends on several factors such as exposure time, age and gender. Inflammation has been considered as one of the main factors associated with the generation of these diseases. Here we present some cellular mechanisms activated by air pollution that may represent risk factors for epilepsy and drug resistance associated to epilepsy.

20.
Pharmacol Res ; 150: 104413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31449975

RESUMO

The high occurrence of atherosclerotic cardiovascular disease (ASCVD) events is still a major public health issue. Although a major determinant of ASCVD event reduction is the absolute change of low-density lipoprotein-cholesterol (LDL-C), considerable residual risk remains and new therapeutic options are required, in particular, to address triglyceride-rich lipoproteins and lipoprotein(a) [Lp(a)]. In the era of Genome Wide Association Studies and Mendelian Randomization analyses aimed at increasing the understanding of the pathophysiology of ASCVD, RNA-based therapies may offer more effective treatment options. The advantage of oligonucleotide-based treatments is that drug candidates are targeted at highly specific regions of RNA that code for proteins that in turn regulate lipid and lipoprotein metabolism. For LDL-C lowering, the use of inclisiran - a silencing RNA that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis - has the advantage that a single s.c. injection lowers LDL-C for up to 6 months. In familial hypercholesterolemia, the use of the antisense oligonucleotide (ASO) mipomersen, targeting apolipoprotein (apoB) to reduce LDL-C, has been a valuable therapeutic approach, despite unquestionable safety concerns. The availability of specific ASOs lowering Lp(a) levels will allow rigorous testing of the Lp(a) hypothesis; by dramatically reducing plasma triglyceride levels, Volanesorsen (APOC3) and angiopoietin-like 3 (ANGPTL3)-LRx will further clarify the causality of triglyceride-rich lipoproteins in ASCVD. The rapid progress to date heralds a new dawn in therapeutic lipidology, but outcome, safety and cost-effectiveness studies are required to establish the role of these new agents in clinical practice.

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