Sleep deprivation induces late deleterious effects in a pharmacological model of Parkinsonism.

Parkinson's disease is a degenerative, chronic and progressive disease, characterized by motor dysfunctions. Patients also exhibit non-motor symptoms, such as affective and sleep disorders. Sleep disorders can potentiate clinical and neuropathological features and lead to worse prognosis. The goal of this study was to evaluate the effects of sleep deprivation (SD) in mice submitted to a progressive pharmacological model of Parkinsonism (chronic administration with a low dose of reserpine). Male Swiss mice received 20 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. SD was applied before or during reserpine treatment and was performed by gentle handling for 6 h per day for 10 consecutive days. Animals were submitted to motor and non-motor behavioral assessments and neurochemical evaluations. Locomotion was increased by SD and decreased by reserpine treatment. SD during treatment delayed the onset of catalepsy, but SD prior to treatment potentiated reserpine-induced catalepsy. Thus, although SD induced an apparent beneficial effect on motor parameters, a delayed deleterious effect on alterations induced by reserpine was found. In the object recognition test, both SD and reserpine treatment produced cognitive deficits. In addition, the association between SD and reserpine induced anhedonic-like behavior. Finally, an increase in oxidative stress was found in hippocampus of mice subjected to SD, and tyrosine hydroxylase immunoreactivity was reduced in substantia nigra of reserpine-treated animals. Results point to a possible late effect of SD, aggravating the deficits in mice submitted to the reserpine progressive model of PD.

Animal Approaches to Studying Risk Factors for Parkinson's Disease: A Narrative Review.

Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson's disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease's etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment.

Vascular ligations for control of postpartum hemorrhage / Ligaduras vasculares para el control de la hemorragia posparto

Objective: To present a case series of 26 patients with postpartum hemorrhages treated with vascular ligations and analyze its efficiency for hemorrhagic control.Material and methods: This case series included patients with postpartum hemorrhages hospitalized in a high risk pregnancy unit in Sofia Feldman Hospital, Brazil, between January 2014 and May 2017, who were treated with vascular ligation techniques. The data were collected from patient medical records.Results: The success rate in hemorrhagic control was 96.2% and hemorrhagic control of the single case in which vascular ligation failed was obtained with total hysterectomy. Hypovolemic shock occurred in 19.2% of the patients and blood transfusion was required in 26.9%. No patient required intensive care unit treatment. Hypertensive syndrome was the most prevalent comorbidity (46.2%). The main etiology was uterine atony (65.4%). Uterine and/or pelvic adhesions and uterine lacerations associated with fetal extraction occurred in 19.3% and 15.4% of cases, respectively. Conclusion: Vascular ligations are efficient strategies for hemorrhagic control during cesarean sections and should be an integral part of the set of techniques that allow uterus preservation in the treatment of postpartum hemorrhage.(AU)

Objetivo: Presentar una serie de casos de 26 pacientes con hemorragias posparto tratadas con ligaduras vasculares y analizar su eficacia para el control hemorrágico. Material y métodos: Esta serie de casos incluyó a pacientes con hemorragias posparto hospitalizadas en la Unidad de Embarazo de Alto Riesgo del Hospital Sofia Feldman, Brasil, entre enero de 2014 y mayo de 2017, que fueron tratadas con técnicas de ligaduras vasculares. Los datos se obtuvieron de los registros médicos de las pacientes. Resultados: La tasa de éxito en el control hemorrágico fue del 96,2% y el control hemorrágico del caso único en el que falló la ligadura vascular, se obtuvo con histerectomía total. El choque hipovolémico ocurrió en el 19,2% de los pacientes y se requirió transfusión de sangre en el 26,9%. Ningún paciente requirió tratamiento en la Unidad de Cuidados Intensivos. El síndrome hipertensivo fue la comorbilidad con mayor prevalencia (46,2%). La principal etiología fue la atonía uterina (65,4%). Las adherencias uterinas y/o pélvicas y las laceraciones uterinas asociadas con la extracción fetal ocurrieron en el 19,3% y el 15,4% de los casos, respectivamente. Conclusión: Las ligaduras vasculares son estrategias eficaces para el control hemorrágico durante la cesárea y deben integrar el conjunto de técnicas que permiten la preservación del útero en el tratamiento de la hemorragia posparto.(AU)

Biosynthesis and characterization of gold nanoparticles using Brazilian red propolis and evaluation of its antimicrobial and anticancer activities.

Gold nanoparticles (AuNPs) are highlighted due to their low toxicity, compatibility with the human body, high surface area to volume ratio, and surfaces that can be easily modified with ligands. Biosynthesis of AuNPs using plant extract is considered a simple, low-cost, and eco-friendly approach. Brazilian Red Propolis (BRP), a product of bees, exhibits anti-inflammatory, anti-tumor, antioxidant, and antimicrobial activities. Here, we described the biosynthesis of AuNPs using BRP extract (AuNPextract) and its fractions (AuNPhexane, AuNPdichloromethane, AuNPethyl acetate) and evaluated their structural properties and their potential against microorganisms and cancer cells. AuNPs showed a surface plasmon resonance (SPR) band at 535 nm. The sizes and morphologies were influenced by the BRP sample used in the reaction. FTIR and TGA revealed the involvement of bioactive compounds from BRP extract or its fractions in the synthesis and stabilization of AuNPs. AuNPdichloromethane and AuNPhexane exhibited antimicrobial activities against all strains tested, showing their efficacy as antimicrobial agents to treat infectious diseases. AuNPs showed dose-dependent cytotoxic activity both in T24 and PC-3 cells. AuNPdichloromethane and AuNPextract exhibited the highest in vitro cytotoxic effect. Also, the cytotoxicity of biogenic nanoparticles was induced by mechanisms associated with apoptosis. The results highlight a potential low-cost green method using Brazilian red propolis to synthesize AuNPs, which demonstrated significant biological properties.

Inappropriate screening of obstructive coronary artery disease during pre-anesthesia assessment of candidates for non-cardiac surgery.

Preoperative evaluation in elective surgeries has been associated with successful surgical treatment. However, there is no solid scientific evidence that screening for coronary artery disease (CAD) reduces surgical risk. The aims of this study were to describe the frequency of inappropriate investigation of obstructive CAD induced by pre-anesthetic assessment in individuals without cardiovascular symptoms (candidates for low- to intermediate-risk surgeries) and to evaluate predictors of this conduct. We performed a retrospective evaluation of medical records of anesthesiology services from patients undergoing pre-anesthesia assessment between May 2015 and May 2016, including those with functional capacity ≥4 metabolic equivalents without a diagnosis of heart disease. A total of 778 medical records (47±16 years of age, 62.6% female) were studied. A private hospital performed 50.1% of the surgeries and 60.4% were of intermediate risk. Only 2.7% (95%CI: 1.7-4.1%) were screened for CAD, and 91% of these requests were mediated by cardiology consultations performed during pre-anesthetic testing visits. Factors associated with screening for CAD were hypertension, diabetes, moderate systemic disease (ASA III), cardiac consultation, previous diagnosis of CAD, and admission to a private hospital. Independent predictors were private hospitals (OR: 3.9; 95%CI: 1.3-11.0), ASA III (OR: 5.3; 95%CI: 1.7-16.2), and hypertension (OR: 3.8; 95%CI: 1.5-9.8). The frequency of inappropriate requests for CAD screening in asymptomatic individuals without untreated systemic diseases was low in pre-anesthetic visits. Although infrequent, screening for CAD is more common in the private setting, in patients with poorer health status, and is usually prescribed during cardiology consultation.

Inappropriate screening of obstructive coronary artery disease during pre-anesthesia assessment of candidates for non-cardiac surgery

Preoperative evaluation in elective surgeries has been associated with successful surgical treatment. However, there is no solid scientific evidence that screening for coronary artery disease (CAD) reduces surgical risk. The aims of this study were to describe the frequency of inappropriate investigation of obstructive CAD induced by pre-anesthetic assessment in individuals without cardiovascular symptoms (candidates for low- to intermediate-risk surgeries) and to evaluate predictors of this conduct. We performed a retrospective evaluation of medical records of anesthesiology services from patients undergoing pre-anesthesia assessment between May 2015 and May 2016, including those with functional capacity ≥4 metabolic equivalents without a diagnosis of heart disease. A total of 778 medical records (47±16 years of age, 62.6% female) were studied. A private hospital performed 50.1% of the surgeries and 60.4% were of intermediate risk. Only 2.7% (95%CI: 1.7-4.1%) were screened for CAD, and 91% of these requests were mediated by cardiology consultations performed during pre-anesthetic testing visits. Factors associated with screening for CAD were hypertension, diabetes, moderate systemic disease (ASA III), cardiac consultation, previous diagnosis of CAD, and admission to a private hospital. Independent predictors were private hospitals (OR: 3.9; 95%CI: 1.3-11.0), ASA III (OR: 5.3; 95%CI: 1.7-16.2), and hypertension (OR: 3.8; 95%CI: 1.5-9.8). The frequency of inappropriate requests for CAD screening in asymptomatic individuals without untreated systemic diseases was low in pre-anesthetic visits. Although infrequent, screening for CAD is more common in the private setting, in patients with poorer health status, and is usually prescribed during cardiology consultation.

Cryptococcosis in HIV-AIDS patients from Southern Brazil: Still a major problem.

INTRODUCTION: Cryptococcus neoformans is an opportunistic pathogen that causes ∼15% mortality in AIDS patients. Rio Grande City, Rio Grande do Sul (RS), Brazil, has the highest national rate of HIV/AIDS, considering cities with population more than 100,000 habitants. OBJECTIVE: We aimed to evaluate the clinical and epidemiological profile of cryptococcosis in a reference service for HIV-AIDS patients in the South region of Brazil, over seven years. Material and methods A retrospective study was performed including all cryptococcosis cases diagnosed at the University Hospital, Federal University of Rio Grande (UH-FURG) between January 2010 and December 2016. RESULTS: Seventy cases of cryptococcosis were diagnosis from 2010 to 2016 in the UH-FURG in the seven years of the study. These numbers were responsible for 2.1% to 8.1% of the hospitalizations/year for HIV patients. All were caused by C. neoformans infection (95% C. neoformans var. grubii VNI and 5% C. neoformans var. grubii VNII). Neurocryptococcosis was the major clinical manifestation and cryptococcosis was the HIV- defining condition in 40% of patients. The period of hospitalization was an average of 39.3 days (SD=31.3), and more than half of patients (53%; 37/70) died after a mean of 82 days. DISCUSSION: The present study showed the importance of cryptococcosis as an AIDS-defining disease in HIV-AIDS patients in a tertiary hospital from Southern Brazil. More investment is necessary to reduce the impact of this opportunistic mycosis in HIV-AIDS patients from southern Brazil.

Targeted uptake of folic acid-functionalized polymeric nanoparticles loading glycoalkaloidic extract in vitro and in vivo assays.

Solanum lycocarpum fruits contain two major glycoalkaloids (GAs), solamargine (SM) and solasonine (SS). These compounds are reported as cytotoxic. However, they have poor water solubility and low bioavailability. To overcome these disadvantages and getting an efficient formulation the current study aimed to develop, characterize, and test the effectiveness of a nanotechnology-based strategy using poly(D,L-lactide) (PLA) nanoparticles functionalized with folate as delivery system of glycoalkaloidic extract (AE) for bladder cancer therapy. The strategic of adding folic acid into nanoformulations can increase the selectivity of the compounds to the cancer cells reducing the side effects. Our results revealed the successful preparation of AE-loaded folate-targeted nanoparticles (NP-F-AE) with particle size around 177 nm, negative zeta potential, polydispersity index <0.20, and higher efficiency of encapsulation for both GAs present in the extract (>85 %). To investigate the cellular uptake, the fluorescent dye coumarin-6 was encapsulated into the nanoparticle (NP-F-C6). The cell studies showed high uptake of nanoparticles by breast (MDA-MB-231) and bladder (RT4) cancer cells, but not for normal keratinocytes cells (HaCaT) indicating the target uptake to cancer cells. The cytotoxicity of nanoparticles was evaluated on RT4 2D culture model showing 2.16-fold lower IC50 than the free AE. Furthermore, the IC50 increased on the RT4 spheroids compared to 2D model. The nanoparticles penetrated homogeneously into the urotheliumof porcine bladder. These results showed that folate-conjugated polymeric nanoparticles are potential carriers for targeted glycoalkaloidic extract delivery to bladder cancer cells.

Padronização de uma PCR para diagnóstico molecular de Microsporum canis em amostras de pelos e crostas de cães e gatos / Standardization of a pcr for molecular diagnosis of microsporum canis in samples of fur and crusts of dogs and cats

Objetivou-se neste estudo padronizar um protocolo de reação em cadeia da polimerase (PCR) para detecção de Microsporum canis em amostras de pelos e/ou crostas de cães e gatos. Foram selecionadas 48 amostras previamente identificadas por meio de cultura. Destas, 23 foram positivas para dermatófitos no cultivo. Padronizou-se a PCR a partir de primers desenhados para o alvo M. canis. Sessenta e um por cento (14/23) das amostras positivas para dermatófitos foram identificadas como M. canis em cultura. Desse total, 71,4% (10/14) apresentaram um fragmento de 218pb compatível com o esperado para a espécie fúngica alvo dessa reação. Observou-se uma sensibilidade de 71,4% e especificidade de 100% na PCR, além de uma boa concordância entre essas técnicas de diagnóstico (Kappa: 0,78; P<0,0001). O protocolo utilizado neste estudo apresentou alta especificidade na detecção de M. canis diretamente de amostras de pelos e/ou crostas de cães e gatos, viabilizando um diagnóstico mais rápido e específico, podendo esse protocolo ser empregado como um método confirmatório para agilizar a detecção de M. canis.(AU)

The aim of this study was to standardize a Polymerase Chain Reaction protocol (PCR) for the detection of Microsporum canis in fur and/or crusts of dogs and cats. 48 samples previously identified by culture were selected. Of these, 23 were positive for dermatophytes in culture. PCR was standardized from drawn primers whose target is M. canis. A total of 61% (14/23) of the dermatophyte positive samples were identified as M. canis in culture. Of this total, 71.4% (10/14) presented a fragment of 218bp compatible with that expected for the fungal species target of the reaction. A sensitivity of 71.4% and specificity of 100% in the PCR were observed, in addition to a good agreement between the techniques (Kappa: 0.78; P<0.0001). The protocol used in this study showed high specificity in the detection of M. canis directly from fur and/or crusts of dogs and cats, making possible a faster and more specific diagnosis. This protocol could be used as a confirmatory method, speeding the detection of M. canis.(AU)

A new acridone with antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans.

AIM: The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. METHODS AND RESULTS: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7·81-31·25 µg ml-1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. CONCLUSIONS: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.

My Loved One Was Not an Organ Donor: Ethical Dilemmas for Family Members of Deceased Potential Donors When Making the Decision on Donation.

OBJECTIVE: The study focuses on the experience of family members of deceased potential donors in deciding to refuse donation when their loved one had expressed his or her wish in life not to donate organs and tissues for transplantation. METHOD: This is a qualitative study that uses social phenomenology as the theoretical reference, interviewing 8 family members of deceased potential donors. RESULTS: The family members' experiences were represented by the following categories: beliefs related to donation, fear in the face of the loved one's death, and the ethical dilemma of deciding to refuse the donation. The meaning of the refusal to donate was represented by the following categories: respect for the loved one's wishes and the family's peace of mind with the decision. CONCLUSIONS: The study shed light on the experience of family members of deceased potential donors in making the decision to refuse donation. The concerns that motivate refusal were elucidated and the meanings of the decision's intentionality were unveiled. The resulting knowledge about these families' experiences provides backing for experts in donation and transplantation who work in different realities, pointing to strategies for improving care for such family members.