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.

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.

Biochemical studies of amylase, lipase and protease in Callosobruchus maculatus (Coleoptera: Chrysomelidae) populations fed with Vigna unguiculata grain cultivated with diazotrophic bacteria strains.

The objective of this study was to evaluate the enzymatic activity of homogenates of insects fed on grain of cowpea, Vigna unguiculata (L.), cultivars grown with different nitrogen sources. For the experiment we used aliquots of the homogenate of 100 unsexed adult insects, emerged from 10 g of grain obtained from four cowpea cultivars: 'BRS Acauã', 'BRS Carijó', 'BRS Pujante', and 'BRS Tapaihum' grown under different regimes of nitrogen sources: mineral fertilizer, inoculation with strains of diazotrophs (BR 3267, BR 3262, BR 3299; INPA 03-11B, 03-84 UFLA, as well as the control (with soil nitrogen). The parameters evaluated were enzymatic activities of insect protease, amylase and lipase and the starch content of the grains. There were differences in the enzymatic activity of amylase, lipase and protease of insect homogenate according to the food source. A lower activity of the enzyme amylase from C. maculatus homogenate was observed when insects were fed grain of the cultivar BRS Carijó. A lower activity of lipase enzyme from C. maculatus homogenate was observed when the insects fed on grain from the interaction of the cultivar Tapaihum inoculated with BR 3262 diazotrophs. The lowest proteolytic activity was observed in homogenate of insects fed on interaction of 'BRS Carijó' inoculated with BR 3262 diazotrophs. Starch content correlated positively with the amylase activity of C. maculatus homogenate. The cultivar BRS Carijó had a different behavior from the other cultivars, according to the cluster analysis.

Sensory and physicochemical evaluation of low-fat chicken mortadella with added native and modified starches.

The objective of this work was to evaluate the effect of adding different starches (native and modified) on the physicochemical, sensory, structural and microbiological characteristics of low-fat chicken mortadella. Two formulations containing native cassava and regular corn starch, coded CASS (5.0 % of cassava starch) and CORN (5.0 % of regular corn starch), and one formulation produced with physically treated starch coded as MOD1 (2.5 % of Novation 2300) and chemically modified starch coded as MOD2 (2.5 % of Thermtex) were studied. The following tests were performed: physicochemical characterization (moisture, ash, protein, starch and lipid contents, and water activity); cooling, freezing and reheating losses; texture (texture profile test); color coordinates (L*, a*, b*, C and h); microbiological evaluation; sensory evaluation (multiple comparison and preference test); and histological evaluation (light microscopy). There was no significant difference (p > 0.05) for ash, protein, cooling loss, cohesiveness or in the preference test for the tested samples. The other evaluated parameters showed significant differences (p < 0.05). Histological study allowed for a qualitative evaluation between the physical properties of the food and its microscopic structure. The best results were obtained for formulation MOD2 (2.5 % Thermtex). The addition of modified starch resulted in a better performance than the native starch in relation to the evaluated technological parameters, mainly in relation to reheating losses, which demonstrated the good interaction between the modified starch in the structure of the product and the possibility of the application of this type of starch in other types of functional meat products.

Identification and antifungal susceptibility of fungi isolated from dermatomycoses.

BACKGROUND: Dermatomycoses are superficial fungal infections of the skin, hair and nails that affect more than 20-25% of the people worldwide. These infections can be caused by yeasts, dermatophytes and non-dermatophyte filamentous fungi (NDFF) and are considered a public health problem. Despite this, few studies have investigated the prevalence and antifungal susceptibility of causative agents of dermatomycoses in the developing world. OBJECTIVES: The aims of this study were to identify and determine the antifungal susceptibility profile of yeast and filamentous fungi isolated from dermatomycoses in Uberaba, Minas Gerais, Brazil. METHODS: Specimens were obtained from patients with clinically diagnosed and laboratory confirmed dermatomycosis between July 2009 and July 2011. Fungal identification was based on classical methods and antifungal susceptibility testing was performed by broth microdilution method. RESULTS: Of the 216 fungal isolates, 116 (53.8%) were yeasts, 70 (32.4%) dermatophytes and 30 (13.8%) NDFF. Onychomycosis was the most common clinical condition. Candida parapsilosis (24.1%) and Trichophyton rubrum (17.1%) were the fungi most frequently isolated. Voriconazole, ketoconazole and itraconazole were the most potent antifungal agents against yeast, whereas terbinafine, voriconazole and itraconazole had a high in vitro activity against dermatophytes. Overall, the antifungal agents had little or no activity against NDFF and the highest minimum inhibitory concentrations were those against Fusarium spp. CONCLUSION: Yeasts, particularly C. parapsilosis, play an important role as causative agents of dermatomycosis in our region. Our results suggest that the antifungal susceptibility testing coupled with proper identification of the fungi may be useful to assist clinicians in determining the appropriate therapy for dermatomycoses.

DNA damage in Wistar rats exposed to dithiocarbamate pesticide mancozeb.

Pesticides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to public and environmental health. The aim of the present study was to investigate the genotoxic potential of a commercial formulation of the fungicide mancozeb by the micronucleus test in bone marrow and the comet assay in total blood of Wistar rats. Adult male Wistar rats were treated with a solution of mancozeb at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days, and compared to a control group. The results indicate that mancozeb induced significantly higher DNA damage as detected by the comet assay and increased the frequency of micronuclei. The results show that mancozeb is genotoxic and may adversely affect the DNA integrity of exposed organisms.

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.

Core level (S 2p) excitation and fragmentation of the dimethyl sulfide and dimethyldisulfide molecules.

Electronic excitation and ionic dissociation of dimethylsulfide (DMS) and dimethyldisulfide (DMDS) have been studied around the S 2p edge using synchrotron radiation and time-of-flight mass spectrometry techniques. Mass spectra were obtained for both molecules, below, on and above the well defined resonances observed in the S 2p photoabsorption spectrum and centered at approximately 166 eV photon energy. Ab initio IS-CASSCF calculations were performed for a better understanding of the photoabsorption spectra. Similar calculations were also performed for the H(2)S molecule, in order to establish a bench mark. For both molecules, a higher fragmentation degree is observed with increasing photon energy. In the DMDS case, selective fragmentation was observed in the formation of the [CH(n)S](+) ions at the first S 2p resonance (corresponding to excitation to a σ*SS state) and in the formation of the [S(2)](+) and [S](+) ions at the third S 2p resonance (corresponding to excitation to a σ*CS state). Previously unreported doubly charged ([S](2+), [CH(3)](2+)) are observed for DMS and DMDS.

Probiotic cheese attenuates exercise-induced immune suppression in Wistar rats.

Intense physical activity results in a substantial volume of stress and hence a significant probability of immunosuppression in athletes, with milk proteins being, perhaps, the most recommended protein supplements. Consumption of a probiotic cheese can attenuate immune suppression induced by exhausting exercise in rats. A popular Brazilian fresh cheese (Minas Frescal cheese) containing Lactobacillus acidophilus LA14 and Bifidobacterium longum BL05 was fed for 2wk to adult Wistar rats, which then were brought to exhaustion on the treadmill. Two hours after exhaustion, the rats were killed and material was collected for the determination of serum uric acid, total and high-density lipoprotein cholesterol fraction, total protein, triacylglycerols, aspartate aminotransferase, alanine aminotransferase, creatine kinase, and blood cell (monocyte, lymphocyte, neutrophil, and leukocyte) counts. Exercise was efficient in reducing lymphocyte counts, irrespective of the type of ingested cheese, but the decrease in the group fed the probiotic cheese was 22% compared with 48% in the animals fed regular cheese. Monocyte counts were unaltered in the rats fed probiotic cheese compared with a significant decrease in the rats fed the regular cheese. Most importantly, ingestion of the probiotic cheese resulted in a >100% increase in serum high-density lipoprotein cholesterol and a 50% decrease in triacylglycerols. We conclude that probiotic Minas Frescal cheese may be a viable alternative to enhance the immune system and could be used to prevent infections, particularly those related to the physical overexertion of athletes.

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.

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.

X-ray laser microscopy of rat sperm nuclei.

The development of high brightness and short pulse width (< 200 picoseconds) x-ray lasers now offers biologists the possibility of high-resolution imaging of specimens in an aqueous environment without the blurring effects associated with natural motions and chemical erosion. As a step toward developing the capabilities of this type of x-ray microscopy, a tantalum x-ray laser at 44.83 angstrom wavelength was used together with an x-ray zone plate lens to image both unlabeled and selectively gold-labeled dried rat sperm nuclei. The observed images show approximately 500 angstrom features, illustrate the importance of x-ray microscopy in determining chemical composition, and provide information about the uniformity of sperm chromatin organization and the extent of sperm chromatin hydration.

Flight take-off and walking behavior of insecticide-susceptible and - resistant strains of Sitophilus zeamais exposed to deltamethrin.

Insects have evolved a variety of physiological and behavioral responses to various toxins in natural and managed ecosystems. However, insect behavior is seldom considered in insecticide studies although insects are capable of changing their behavior in response to their sensory perception of insecticides, which may compromise insecticide efficacy. This is particularly serious for insect pests that are physiologically resistant to insecticides since insecticide avoidance may further compromise their management. Locomotion plays a major role determining insecticide exposure and was, therefore, considered in investigating the behavioral responses of male and female adult insects from an insecticide-susceptible and two insecticide-resistant strains of the maize weevil Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), a major pest of stored cereals. Different dose-dependent behavioral responses were expected among strains with behavioral resistance less likely to occur in physiologically resistant insects since they are able to withstand higher doses of insecticide. The behavioral responses to deltamethrin-sprayed surfaces differed among the maize weevil strains. Such responses were concentration-independent for all of the strains. Stimulus-independent behavioral resistance was unrelated to physiological resistance with one resistant strain exhibiting higher rates of flight take-off and the other resistant strain exhibiting lower flight take-off. Female mobility was similar for all strains, unlike male mobility. Males of each strain exhibited a pattern of mobility following the same trend of flight take-off. Behavioral patterns of response to insecticide are, therefore, variable among strains, particularly among insecticide-resistant strains, and worth considering in resistance surveys and management programs.

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.

Bone Tissue Donation: Tendency and Hurdles.

INTRODUCTION: The aim of this study was to identify the percentage of bone tissue donation in a brain death situation and the tendency of donation rate of this tissue in an organ procurement organization in the county of Sao Paulo from 2001 to 2016. It is a retrospective and quantitative study, based on the Organ and Tissue Donation Term of donors who died of brain death between 2001 and 2016. METHODS: A logistic regression model was applied, and the odds of donation were identified throughout the years, regarding the odds ratio different from zero. Finally, it was measured the accuracy of the odds ratio through the confidence interval. RESULTS: The analysis has shown a significant change on the trend of bone donation (P < .001). In this case, the odds ratio was >1, indicating that the donation rate has increased. However, the percentage of growth is still considered low. CONCLUSIONS: The study evidences a growth trend regarding the donation of bone tissue, but the percentage is still too low to adequately meet the demand of patients who need this modality of therapeutic intervention. It is believed that educational campaigns of donation are not emphasizing the donation of tissues for transplantation, which may be directly impacting their consent rates.

Family Interview to Enable Donation of Organs for Transplantation: Evidence-based Practice.

BACKGROUND: In this study we propose a theoretical and practical basis for the best practices for interviewing relatives of brain-dead eligible organ donors. METHODS: This investigation was a reflective study of the methodologic factors of the family interview that affect their decision regarding the donation of a deceased patient's organs for transplantation. The articles that formed the empirical basis of the trial were obtained from PubMed, which is a free-access tool of the MEDLINE database of the United States National Library of Medicine. Published articles that allowed us to reflect on evidence-based family interview practice were selected. RESULTS: Thirty-six scientific articles were used to guide our assessment the family interview, providing evidence for its adequate execution in view of the following prerequisites: When should the family interview be performed? Where should it be done? How many and which people should participate in the interview? Who should perform it? How should it be done? CONCLUSION: Scientific studies offer evidence to donation and transplantation specialists that can help them in their daily work regarding their interactions with relatives in the process of decisionmaking and family consent.