Improved Sleep, Memory, and Cellular Pathological Features of Tauopathy, Including the NLRP3 Inflammasome, after Chronic Administration of Trazodone in rTg4510 Mice.

Several cellular pathways contribute to neurodegenerative tauopathy-related disorders. Microglial activation, a major component of neuroinflammation, is an early pathologic hallmark that correlates with cognitive decline, while the unfolded protein response (UPR) contributes to synaptic pathology. Sleep disturbances are prevalent in tauopathies and may also contribute to disease progression. Few studies have investigated whether manipulations of sleep influence cellular pathologic and behavioral features of tauopathy. We investigated whether trazodone, a licensed antidepressant with hypnotic efficacy in dementia, can reduce disease-related cellular pathways and improve memory and sleep in male rTg4510 mice with a tauopathy-like phenotype. In a 9 week dosing regimen, trazodone decreased microglial NLRP3 inflammasome expression and phosphorylated p38 mitogen-activated protein kinase levels, which correlated with the NLRP3 inflammasome, the UPR effector ATF4, and total tau levels. Trazodone reduced theta oscillations during rapid eye movement (REM) sleep and enhanced REM sleep duration. Olfactory memory transiently improved, and memory performance correlated with REM sleep duration and theta oscillations. These findings on the effects of trazodone on the NLRP3 inflammasome, the unfolded protein response and behavioral hallmarks of dementia warrant further studies on the therapeutic value of sleep-modulating compounds for tauopathies.SIGNIFICANCE STATEMENT Dementia and associated behavioral symptoms such as memory loss and sleep disturbance are debilitating. Identifying treatments that alleviate symptoms and concurrently target cellular pathways contributing to disease progression is paramount for the patients and their caregivers. Here we show that a chronic treatment with trazodone, an antidepressant with positive effects on sleep, has beneficial effects on several cellular pathways contributing to neuroinflammation and tau pathology, in tauopathy-like rTg4510 mice. Trazodone also improved rapid eye movement (REM) sleep, the slowing of brain oscillations, and olfactory memory disturbances, which are all early symptoms observed in Alzheimer's disease. Thus, trazodone and compounds with REM sleep-promoting properties may represent a promising treatment approach to reduce the early symptoms of tauopathy and slow down disease progression.

Treatment patterns and outcomes for Hodgkin Lymphoma patients aged 60 and older: a report from the Brazilian Prospective Hodgkin Lymphoma Registry.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.

Metabolomic profile of seminal plasma from Guzerá bulls (Bos indicus) with contrasting sperm freezability phenotypes.

The present study evaluated the seminal plasma metabolome of Bos indicus Guzerá bulls with good (n = 4) and poor (n = 5) sperm freezability. Animals were raised in natural pasture of a 'Caatinga' ecosystem, in the semi-arid region of Brazil. Seminal plasma samples were subjected to gas chromatography coupled to mass spectrometry and data, analysed using bioinformatics tools (Cytoscape with the MetScape plug-in). Sixty-two metabolites were identified in the bovine seminal plasma. Fatty acids and conjugates and organic compounds were the predominant seminal fluid metabolites, followed by carboxylic acids and derivatives, amino acids, benzenes and steroids and derivatives, carbohydrates and carbohydrate conjugates and prenol lipids. Multivariate analysis indicated a distinct separation of seminal plasma metabolomes from bulls with contrasting sperm freezability. Abundances of propanoic acid, d-ribose and glycine were greater in the seminal plasma of bulls with good sperm freezability. Heptadecanoic acid and undecanoic acid were the predominant in bulls of poor sperm freezability. Propanoic acid is an energy source for spermatozoa and may act as an antimicrobial component in semen. Glycine acts against oxidizing and denaturing reactions. d-ribose is also an energy source and reduces apoptosis and oxidative stress. Undecanoic acid may protect sperm against fungal damage. This study provides fundamental information approximately the seminal plasma metabolome of tropically adapted bulls and its association with sperm freezability. However, further studies with larger groups of animals are needed to validate those metabolites as markers of sperm freezability. This strategy could support the selection of sires with superior sperm cryoresistance.

Radiographic study of the axial and appendicular skeleton of Callithrix jacchus and Callithrix penicillata.

BACKGROUND: Marmosets are small arboreal primates. Knowledge of normal radiographic parameters and frequent disorders is limited. The objectives of this study were to evaluate possible variations between quantitative analyses and injuries to the appendicular and axial skeleton of Callithrix jacchus and Callithrix penicillata and their relationship with the environment. METHODS: Radiographic images of 29 marmosets were used. Skeletal lesions were described, long bones were measured, and pelvimetry, vertebrae, and sternebras were counted. RESULTS: Measurements of long bones and pelvimetry were similar between species. Evaluation of vertebrae and sternebras exhibited variations relative to the literature. Lesions on the skull, spine, thoracic and pelvic limbs were present in 48%, 54%, 44%, and 52% of marmosets, respectively. CONCLUSION: Skeletal disorders, especially of traumatic and metabolic origin, have a high prevalence in marmosets.

Combined conventional speech therapy and functional electrical stimulation in acute stroke patients with dyphagia: a randomized controlled trial.

BACKGROUND: Stroke is the main cause of oropharyngeal neurogenic dysphagia. Electrostimulation has been used as a therapeutic tool in these cases. However, there are few studies that prove its effectiveness. We evaluated the effect of functional electrostimulation as a complement to conventional speech therapy in patients with dysphagia after a stroke in a stroke unit. METHODS: We performed a clinical, randomized, and controlled trial divided into intervention group (IG) (n = 16) and control group (CG) (n = 17). All patients were treated with conventional speech therapy, and the IG also was submitted to the functional electrotherapy. Primary outcomes were Functional Oral Ingestion Scale (FOIS) and Swallowing videoendoscopy (FEES). The degree of dysphagia was scored in functional, mild, moderate and severe dysphagia according to FEES procedure. Dysphagia Risk Evaluation Protocol (DREP) was considered a secondary outcome. RESULTS: There was a significant difference regarding FOIS scores after 5 days of intervention in groups. Both groups also showed a tendency to improve dysphagia levels measured by FEES, although not statistically significant. Improvements on oral feeding was seen in both groups. No significant differences between groups before and after the intervention were detected by DREP scores. Electrical stimulation did not show additional benefits beyond conventional therapy when comparing outcomes between groups. CONCLUSION: Conventional speech therapy improved oral ingestion even regardless the use of electrostimulation in a stroke unit. TRIAL REGISTRATION: This research was registered in ClinicalTrials.gov (Identifier: NCT03649295 ) in 28/08/2018 and in the Brazilian Registry of Clinical Trials (ReBEC) (Register Number: RBR-56QK5J), approval date: 18/12/2018. HGF Ethics Committee Approval Number: N. 2.388.931.

Wheezing trajectories from childhood to adulthood in a population-based cohort.

BACKGROUND: Wheezing may lead to asthma and reduced pulmonary function in later life. The study aims to identify wheezing trajectories and investigate their relation with pulmonary function and asthma-related outcomes at 22 years of age. METHODS: Individuals from a population-based cohort in Brazil (1993 Pelotas Birth Cohort) with post-bronchodilator pulmonary function data at 22 years (3350) were included in the study. From parentally reported (4 and 11 years) and self-reported (15, 18 and 22 years) history of wheezing in the last 12 months, we used a group-based trajectory modelling approach to derive wheezing trajectories. RESULTS: Four trajectories were identified: never/infrequent, transient-early, late-onset and persistent wheeze. After adjustments, wheezing trajectories remained associated with lower post-bronchodilator values of pulmonary function. Individuals in the persistent wheeze trajectory had a markedly poorer pulmonary function and also showed greater odds of asthma-related outcomes compared to other trajectories groups. Those following this trajectory had on average -109 ml (95% CI: -188; -35), -1.80 percentage points (95% CI: -2.73; -0.87) and -316 ml/s (95% CI: -482; -150) lower FEV1, FEV1/FVC ratio and FEF25-75% respectively; higher odds of self-reported medical diagnosis of allergy (OR 6.18; 95% CI: 3.59; 10.61) and asthma (OR 12.88; 95% CI: 8.91; 18.61) and asthma medication use (OR 9.42; 95% CI: 5.27; 16.87) compared to the never/infrequent group. CONCLUSIONS: Wheezing trajectories, especially the persistent wheeze trajectory, were related to lower pulmonary function values and increased risk of asthma and allergy diagnosis in early adulthood.

In situ synthesis of Fe3O4 nanoparticles coated by chito-oligosaccharides: physico-chemical characterizations and cytotoxicity evaluation for biomedical applications.

Fe3O4 nanoparticles coated with chito-oligosaccharides (COS) were prepared in situ by a simple co-precipitation method through a mixing of iron ions (Fe3+ and Fe2+) and COS aqueous solutions followed by precipitation with ammonia. The impact of COS with different degree of polymerization (DP 10, 24 and 45) and degree of N-acetylation (DA) âˆ¼ 24% and 50% (exhibiting high solubility) on the synthesis and physical properties of the coated magnetic nanoparticles was evaluated. Several advantages were found when the magnetic nanoparticles were prepared in the presence of the studied COS, such as: preparation of functionalized magnetic nanoparticles with narrower size distributions and, consequently, higher saturation magnetization (an increase of up to 22%); and an expressive increasing in the concentration of COS-coated magnetic nanoparticles (up to twice) in the cell viability test in comparison with pure Fe3O4 nanoparticles. Furthermore, among the analyzed samples, the magnetic nanoparticles coated by COS with DA âˆ¼ 50% present a higher cytocompatibility. Our results allow envisioning various biomedical applications, valorizing the use of coated-magnetic nanoparticles for magnetic-field assisted drug delivery, enzyme or cell immobilization, or as a marker for specific cell tracking, among others.

Nanoparticles and Colloidal Hydrogels of Chitosan-Caseinate Polyelectrolyte Complexes for Drug-Controlled Release Applications.

Chitosan-caseinate nanoparticles were synthesized by polyelectrolyte complex (PEC) formation. Caseinate is an anionic micellar nanocolloid in aqueous solutions, which association with the polycationic chitosan yielded polyelectrolyte complexes with caseinate cores surrounded by a chitosan corona. The pre-structuration of caseinate micelles facilitates the formation of natural polyelectrolyte nanoparticles with good stability and sizes around 200 nm. Such natural nanoparticles can be loaded with molecules for applications in drug-controlled release. In the nanoparticles processing, parameters such as the chitosan degree of acetylation (DA) and molecular weight, order of addition of the polyelectrolytes chitosan (polycation) and caseinate (polyanion), and added weight ratio of polycation:polyanion were varied, which were shown to influence the structure of the polyelectrolyte association, the nanoparticle size and zeta potential. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) analyses revealed the chemical structure of hydrogel colloidal systems consisting of nanoparticles that contain chitosan and caseinate. Transmission electron microscopy (TEM) allowed further characterization of the spherical morphology of the nanoparticles. Furtherly, insulin was chosen as a model drug to study the application of the nanoparticles as a safe biodegradable nanocarrier system for drug-controlled release. An insulin entrapment efficiency of 75% was achieved in the chitosan-caseinate nanoparticles.

Use of mycorrhizal fungi releases the application of organic fertilizers to increase the production of leaf vitexin in yellow passion fruit.

BACKGROUND: Low-cost organic fertilizers, such as coconut powder and vermicompost, and arbuscular mycorrhizal fungi (AMF) may benefit the Passiflora edulis f. flavicarpa plant. However, it has not been established whether the joint application of these inputs may increase the production of vitexin and other molecules associated with the phytotherapeutic properties of this plant. Here, we tested the hypothesis that the application of AMF and organic fertilizers maximizes the production of bioactive compounds in leaves of P. edulis. RESULTS: The inoculation of Acaulospora longula into P. edulis grown in fertilization-free soil promoted an increase of 86% in the concentration of leaf vitexin, 10.29% in the concentration of total phenols, and 13.78% in the concentration of total tannins in relation to the AMF-free control, rendering soil fertilization superfluous. CONCLUSION: The application of A. longula increases the production of foliar biomolecules, such as vitexin, in yellow passion fruit plants. Thus, the addition of coconut powder and vermicompost to the substrate composition is not necessary, leading to the commercialized production of phytomass in the herbal medicines industry. © 2019 Society of Chemical Industry.

Prevalence and associated factors of supine sleep position in 3-month-old infants: findings from the 2015 Pelotas (Brazil) Birth Cohort.

BACKGROUND: Non-supine infant sleep position is an important modifiable risk factor for sudden unexpected death in infancy. The aim of this study was to assess the prevalence of supine sleep position and associated factors among 3-month-old infants from a birth cohort in the city of Pelotas, southern Brazil. METHODS: The present study evaluated longitudinal data from the 2015 Pelotas Birth Cohort. Study outcome was supine infant sleep position, defined as the appropriate position, among 3-month-old children. Demographic, socioeconomic, behavioral, and health characteristics collected at birth and at the 3-month follow-up were investigated as possible associated factors. The prevalence of each associated factor was investigated, and crude and hierarchical adjusted analyses were performed using Poisson regression. RESULTS: Among the 4108 infants assessed in this study, 2274 (55.4%) slept in supine position at 3 months and only 66 (1.6%) in prone position. Maternal white skin color, higher family income and maternal schooling, advanced maternal age, maternal cohabiting with a partner, receiving counseling from health care professionals and non-bed-sharing were associated with higher prevalence of infants sleeping in supine position at 3 months. All these variables remained associated in our hierarchical adjusted analyses except maternal cohabitation with a partner. Participants with white mothers were more likely to sleep in supine position (PR: 1.23; 95%CI: 0.75-0.89) compared to participants with black mothers. Those belonging to the richest quintile were more likely to sleep in supine position (PR: 1.49; 95%CI: 1.35-1.65) compared to those who belong to the poorest. Mothers aged 31-36 years were more likely to choose supine sleep position (PR: 1.65; 95%CI: 1.42-1.92) compared to mothers younger than 19 years. CONCLUSIONS: The findings of the present study showed the influence of maternal age, socioeconomic status, and counseling on infant sleep habits as predictors of choice of infant sleep position in a Brazilian population. It is recommended to implement informative campaigns and public policies to at-risk population and to improve recommendations from health care professionals.

Ridge Architecture Preservation Following Minimally Traumatic Exodontia Techniques and Guided Tissue Regeneration.

OBJECTIVE: To compare hard-tissue healing after 3 exodontia approaches. MATERIALS AND METHODS: Premolars of dogs were extracted: (1) flapless, (2) flap, and (3) flap + socket coverage with polytetrafluoroethylene (dPTFE) nonresorbable membrane (flap + dPTFE). Animals were euthanized at 1 and 4 weeks. Amount of bone formation within socket and socket total area were measured. RESULTS: Amount of bone formation revealed significant difference between 1 and 4 weeks; however, there was no differences among groups. Socket total area decreased after 4 weeks, and the flap + dPTFE group showed significantly higher socket total area. As a function of time and group, flap + dPTFE 4 weeks presented similar socket total area values relative to flap + dPTFE at 1 week, and significantly higher socket total area than flapless and flap. The histological sections revealed almost no bone formation within socket after 1 week, which increased for all groups at 4 weeks. CONCLUSION: Socket coverage with polytetrafluoroethylene (dPTFE) membrane showed to effectively preserve bone architecture. Bone formation within sockets was not influenced by tooth extraction technique.

Production of biomolecules of interest to the anxiolytic herbal medicine industry in yellow passionfruit leaves (Passiflora edulis f. flavicarpa) promoted by mycorrhizal inoculation.

BACKGROUND: Our contemporary way of life has led us to consume high amounts of chemically-synthesized allopathic medicinal products and anxiolytics to which a viable alternative is the use of Passiflora-based herbal medicines with composition containing vitexin, a flavonoid with anxiolytic and antidepressant properties. Arbuscular mycorrhizal fungi (AMF) are known for enhancing the production of biomolecules, however, increase production of phytochemistry in Passiflora edulis f. flavicarpa has not been reported in the literature. Our aim was to select AMF to benefit the production of vitexin in leaves of P. edulis by inoculating seedlings in the region of roots with Acaulospora longula, Claroideoglomus etunicatum and Gigaspora albida. RESULTS: The inoculation increased the concentration of vitexin in 63.64% and the inoculation with A. longula also increased the content of flavonoids and total saponins in the leaves in relation to the control. CONCLUSION: The increase in the production of vitexin in the leaf in response to the inoculation with AMF, with emphasis to A. longula, interests the pharmaceutical industry and can generate profit to the production of yellow passionfruit-based anxiolytic herbal medicine. © 2019 Society of Chemical Industry.

Visceral and subcutaneous abdominal adiposity and pulmonary function in 30-year-old adults: a cross-sectional analysis nested in a birth cohort.

BACKGROUND: Several studies have verified body fat distribution in association with pulmonary function (PF), mainly waist circumference, but few have used measures able to distinguish abdominal fat compartments. The present study aims to verify the association of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with PF measures. METHODS: In 1982, all hospital births occurring in Pelotas, Brazil, were identified and those livebirths have been followed. In 2012-13, the cohort participants were evaluated and VAT and SAT measured using ultrasound; forced expiratory volume in the first second (FEV1) or forced vital capacity (FVC) were patronized in z-scores stratified by sex. The associations were verified using crude and adjusted linear regressions. RESULTS: The present analyses comprised 3438 individuals (1721 women). VAT was inversely associated with spirometric parameters, in both crude and adjusted models. SAT showed inverse associations in the crude analyzes in males and a positive trend after adjustment, except for SAT and FVC in males. To each centimeter of VAT, mean adjusted FEV1 z-scores decreased 0.072 (95% CI -0.107; -0.036) in men and 0.127 (95% CI -0.164; -0.090) in women, and FVC z-scores decreased -0.075 (95% CI -0.111; -0.039) and 0.121 (95% CI -0.158; -0.083), in men and women, respectively. CONCLUSIONS: VAT has a consistent inverse association with FEV1 and FVC in both sexes. On the other hand, SAT showed inconsistent results with PF parameters.

What to Do With Recurrent Prolapse After Vaginal Mesh Failure?

STUDY OBJECTIVE: To show that in selected cases laparoscopic sacrocolpopexy can be used for the treatment of recurrent pelvic organ prolapse after vaginal mesh surgery. METHODS: Step-by-step examination of the technique using an educative video. Institutional review board approval was obtained. SETTING: The authors describe two clinical cases of treatment of recurrent pelvic organ prolapse, after a vaginal mesh surgery, using laparoscopic sacrocolpopexy. PATIENTS: A 56-year old patient (para 3, gravida 2) presented with the sentation of bulging in the vagina. On physical examination, the patient had a grade 2-3 vaginal apical prolapse and a stage 4 rectocele. She had a slight mesh contraction but no vaginal extrusion and no pain were reported. Eleven years before, she had a vaginal total hysterectomy for pelvic organ prolapse correction and one year before she had a vaginal prolapse repair using a synthetic mesh. A laparoscopic sacrocolpopexy with bilateral ooforectomy was performed. The second case is of a 54-year old patient (para 2, gravida 2) that presented stress urinary incontinence. On physical examination, the patient had a grade 3 uterine prolapse and grade 2 cystocele. Eleven years before she had a vaginal prolapse repair using a synthetic mesh and a miduretral sling for stress urinary incontinence. Two years before, she had the miduretal sling removed for recurrent urinary infections and dysuria. A laparoscopic sub-total hysterectomy with salpingectomy and ovarian conservation, sacrocolpopexy and a Burch colposuspension was performed. MEASUREMENTS AND MAIN RESULTS: The procedures and postoperative recovery were uneventful. No minor or major complications occurred. The patients were discharged three days after surgery. CONCLUSION: Laparoscopic sacrocolpopexy is a promising approach for the treatment of recurrent pelvic organ prolapse after vaginal mesh surgery. It appears to be feasible, safe, and effective.

Social skills and psychopathic traits in maltreated adolescents.

Child maltreatment has frequently been associated with impaired social skills and antisocial features, but there are still controversies about the effect of each type of maltreatment on social behaviour. The aim of this study was to compare the social functioning and psychopathic traits of maltreated adolescents (MTA) with a control group (CG) and to investigate what types of maltreatments and social skills were associated with psychopathic traits in both groups. The types and intensity of maltreatment were evaluated through the Childhood Trauma Questionnaire (CTQ) in 107 adolescents, divided into the MTA group (n = 66) and non-maltreated youths (n = 41), our CG. The Hare Psychopathy Checklist: Youth Version (PCL: YV) and a detailed inventory for evaluation of social skills in adolescents were also applied in all individuals. MTA presented more psychopathic traits than the CG, in all domains measured by PCL: YV, independently of IQ levels and the presence of psychiatric disorders. Interestingly, the groups did not differ significantly from each other on indicators of social skills. Multiple regression analysis revealed that emotional neglect was the only maltreatment subtype significantly associated with psychopathic traits, more specifically with the PCL: YV interpersonal factor (F1), and that some social skills (empathy, self-control and social confidence) were related to specific psychopathic factors. The results highlight that emotional neglect may be more detrimental to social behaviours than physical and sexual abuse, and that neglected children require more specific and careful attention.

Adjunctive effect of antimicrobial photodynamic therapy in induced periodontal disease. Animal study with histomorphometrical, immunohistochemical, and cytokine evaluation.

Scaling and root planing (SRP) may not always be effective in preventing periodontal disease (PD) progression. The aim of this study was to evaluate the adjunctive effect of antimicrobial photodynamic therapy (aPDT) to SRP on induced PD in rats, analyzing histomorphometrical, immunohistochemical, and immunoenzymatic parameters. Ligatures were placed around the first mandibular molars and second maxillary molars of 60 rats to induce PD. After 14 days, they were removed and the animals were divided into six groups, with nine animals each: G1 = no treatment, G2 = SRP, G3 = light-emitting diode (LED), G4 = SRP + aPDT, G5 = aPDT, and G6 = erythrosine. The animals were euthanized after 3, 7, and 15 days. There were also two control groups (n = 3): without PD (WPD) induction and with maximum PD (PD+). In the histomorphometrical analysis of linear bone loss, G4 showed a statistically significant difference from the other experimental groups after 3 and 15 days. The tartrate-resistant acid phosphatase (TRAP)-positive cell counting was significantly lower in G4 when compared to G2 and PD+ after 3 days. Immunoenzymatic assay shows the values of the ratio (RANKL/OPG × 100). The lowest value is from the WPD group, and the group that received the SRP + aPDT treatment tended to approach this value over time. After 3 days, statistically significant differences were observed between G4 and all other experimental groups, as well as versus PD+ (one-way ANOVA + Tukey's post hoc test were performed, p < 0.05). It was concluded that the adjunctive use of aPDT in combination with SRP showed the best therapeutic results in the treatment of periodontal disease in rats.

Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells.

Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteins in the vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposed to these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation.

The effect of low-level laser on bone healing in critical size defects treated with or without autogenous bone graft: an experimental study in rat calvaria.

OBJECTIVE: The objective of this study was to evaluate the effect of low-level laser (LLL) on bone healing process in surgically created critical size defects in rat calvaria treated with or without autogenous bone graft (AB). MATERIAL AND METHODS: The study was conducted on 40 male rats (Rattusnorvegicus, albinus, Wistar), weighing 250-300 g. For accomplishment of the experimental procedures, the rats were anesthetized with an intramuscular injection of xylazine (0.02 ml/kg) and ketamine hydrochloride (0.4 ml/kg). Acritical size defect with 5-mm diameter was created. The animals were divided into four groups: Group C (Control- filled with blood clot), Group LLL, Group AB (autogenous bone graft), Group AB + LLL (autogenous bone graft and LLL). The animals treated with LLL received applications of LLL at the infrared spectrum wavelength (λ = 810 nm) and energy density of 6 J/cm(2) per point, 60 s per point, adding up to five points on the entire created defect. The animals were euthanized at 30 days postoperatively. After decalcification, each specimen was longitudinally divided into two blocks, exactly along the center of the original surgical defect, processed and embedded in paraffin. Longitudinal serial sections with 6-µm thickness were made, initiating from the center of the original surgical defect. The sections were stained with hematoxylin and eosin (HE) for light microscopy analysis for histomorphometric analysis. RESULTS: Group C presented smaller quantity of new bone formation than Groups LLL (P < 0.01), AB (P < 0.01), and AB + LLL (P < 0.01). CONCLUSIONS: Utilization of LLL favored the healing process in rat calvaria. The quantity of new bone formation with use of the LLL was similar to the autogenous bone graft.

Evaluation of the anti-inflammatory effect of 1,4-dihydropyridine derivatives.

INTRODUCTION: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities. OBJECTIVE: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice. RESULTS: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture. CONCLUSION: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.