Pomegranate sarcotesta lectin (PgTeL) inhibits planktonic growth and disrupts biofilm formed by Cryptococcus neoformans.

AIMS: We investigated the putative fungistatic and fungicidal activities of pomegranate sarcotesta lectin (PgTeL) against Cryptococcus neoformans B3501 (serotype D), specifically the ability of PgTeL to inhibit yeast capsule and biofilm formation in this strain. METHODS AND RESULTS: PgTeL showed a minimum inhibitory concentration of 172.0 µg ml-1, at which it did not exhibit a fungicidal effect. PgTeL concentrations of 4.0-256.0 µg ml-1 reduced biofilm biomass by 31.0%-64.0%. Furthermore, 32.0-256.0 µg ml-1 PgTeL decreased the metabolic activity of the biofilm by 32.0%-93.0%. Scanning electron microscopy images clearly revealed disruption of the biofilm matrix. Moreover, PgTeL disrupted preformed biofilms. At concentrations of 8.0-256.0 µg ml-1, PgTeL reduced metabolic activity in C. neoformans by 36.0%-92.0%. However, PgTeL did not inhibit the ability of B3501 cells to form capsules under stress conditions. CONCLUSIONS: PgTeL inhibited biofilm formation and disrupted preformed biofilms, demonstrating its potential for use as an anticryptococcal agent.

Impact of lead (Pb2+) on the growth and biological activity of Serratia marcescens selected for wastewater treatment and identification of its zntR gene-a metal efflux regulator.

Microorganisms isolated from contaminated areas play an important role in bioremediation processes. They promote heavy metal removal from the environment by adsorbing ions onto the cell wall surface, accumulating them inside the cells, or reducing, complexing, or precipitating these substances in the environment. Microorganism-based bioremediation processes can be highly efficient, low-cost and have low environmental impact. Thus, the present study aimed to select Pb2+-resistant bacteria and evaluate the growth rate, biological activity, and the presence of genes associated with metal resistance. Serratia marcescens CCMA 1010, that was previously isolated from coffee processing wastewater, was selected since was able to growth in Pb2+ concentrations of up to 4.0 mM. The growth rate and generation time did not differ from those of the control (without Pb2+), although biological activity decreased in the first hour of exposure to these ions and stabilized after this period. The presence of the zntR, zntA and pbrA genes was analysed, and only zntR was detected. The zntR gene encodes a protein responsible for regulating the production of ZntA, a transmembrane protein that facilitates Pb2+ extrusion out of the cell. S. marcescens CCMA 1010 demonstrated a potential for use as bioindicator that has potential to be used in bioremediation processes due to its resistance to high concentrations of Pb2+, ability to grow until 24 h of exposure, and possession of a gene that indicates the existence of mechanisms associated with resistance to lead (Pb2+).

Deep inspiration breath hold: dosimetric benefits to decrease cardiac dose during postoperative radiation therapy for breast cancer patients.

Background: Postoperative radiation therapy (RT) is the standard treatment for almost all patients diagnosed with breast cancer. Even with modern RT techniques, parts of the heart may still receive higher doses than those recommended by clinically validated dose limit restrictions, especially when the left breast is irradiated. Deep inspiration breath hold (DIBH) may reduce irradiated cardiac volume compared to free breathing (FB) treatment. This study aimed to evaluate the dosimetric impact on the heart and left anterior descending coronary artery (LAD) in FB and DIBH RT planning in patients with left breast cancer. Materials and methods: A retrospective cohort study of women diagnosed with left-sided breast cancer submitted to breast surgery followed by postoperative RT from 2015 to 2019. All patients were planned with FB and DIBH and hypofractionated dose prescription (40.05 Gy in 15 fractions). Results: 68 patients were included in the study. For the coverage of the planned target volume evaluation [planning target volume (PTV) eval] there was no significant difference between the DIBH versus FB planning. For the heart and LAD parameters, all constraints evaluated favored DIBH planning, with statistical significance. Regarding the heart, median V16.8 Gy was 2.56% in FB vs. 0% in DIBH (p < 0.001); median V8.8 Gy was 3.47% in FB vs. 0% in DIBH (p < 0.001) and the median of mean heart dose was 1.97 Gy in FB vs. 0.92 Gy in DIBH (p < 0.001). For the LAD constraints D2% < 42 Gy, the median dose was 34.87 Gy in FB versus 5.8 Gy in DIBH (p < 0.001); V16.8 Gy < 10%, the median was 15.87% in FB versus 0% in DIBH (p < 0.001) and the median of mean LAD dose was 8.13Gy in FB versus 2.92Gy in DIBH (p < 0.001). Conclusions: The DIBH technique has consistently demonstrated a significant dose reduction in the heart and LAD in all evaluated constraints, while keeping the same dose coverage in the PTV eval.

Polymorphisms in immune-mediator genes and the risk of dengue virus infection: Lights from a systematic revaluation by Bayesian approaches.

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.

Temporal Reduction in COVID-19-Associated Fatality Among Kidney Transplant Recipients: The Brazilian COVID-19 Registry Cohort Study.

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.

Infected Silicone Chin Implant After Implant-Supported Jaw Rehabilitation: Case Report and Literature Review.

This paper reports on an infected silicone chin implant due to the nonideal placement of dental implants, in a female patient aged 67 years old. A patient unsatisfied with her facial profile had received a silicone chin implant 25 years ago and had recently undergone surgery for placement of dental implants in a region close to the silicone implant. The nonideal positioning of dental implants and close contact with the silicone implant led to the absence of osseointegration, with consequent mobility and infection of both. The mobile dental implants and silicone implant were removed. Imaging exams revealed other complications of the silicone implant as bone resorption and formation of a narrow bone layer around the inferior silicone implant border. Alloplastic implants are an option for the esthetic correction of chin deformities. Solid silicone is biocompatible and highly resistant to degradation, with minimal allergic reaction and risk of toxicity. However, several postoperative complications may arise, such as migration or displacement, extrusion, foreign body reaction, bone resorption, heterotopic bone formation, and infection. Precise imaging exams are critical for diagnosis and to indicate the best treatment plan.

Metabolism of [1,6-13 C]glucose in the cerebellum of 18-day-old rats: Comparison with cerebral metabolism.

There is little information on metabolism in developing cerebellum despite the known importance of this region in cognition and motor tasks. Ex vivo 1 H- and 13 C-NMR spectroscopy were used to determine metabolism during late postnatal development in cerebellum and cerebrum from 18-day-old rat pups after intraperitoneal (i.p.) injection of [1,6-13 C]glucose. The concentration of several metabolites in cerebellum was distinctly different than cerebrum; alanine, glutamine, creatine and myo-inositol were higher in cerebellum than cerebrum, the concentrations of lactate, GABA, aspartate and N-acetylaspartate (NAA) were lower in cerebellum than in cerebrum, and levels of glutamate, succinate, choline and taurine were similar in both brain regions. The incorporation of label from the metabolism of [1,6-13 C]glucose into most isotopomers of glutamate (GLU), glutamine (GLN), GABA and aspartate was lower in cerebellum than in cerebrum. Incorporation of label into the C2 position of lactate via the pyruvate recycling pathway was found in both brain regions. The ratio of newly synthesized GLN/GLU was significantly higher in cerebellum than in cerebrum indicating relatively active metabolism via glutamine synthetase in cerebellar astrocytes at postnatal day 18. This is the first study to determine metabolism in the cerebellum and cerebrum of male and female rat brain.

White matter disturbances in phenylketonuria: Possible underlying mechanisms.

White matter pathologies, as well as intellectual disability, microcephaly, and other central nervous system injuries, are clinical traits commonly ascribed to classic phenylketonuria (PKU). PKU is an inherited metabolic disease elicited by the deficiency of phenylalanine hydroxylase. Accumulation of l-phenylalanine (Phe) and its metabolites is found in tissues and body fluids in phenylketonuric patients. In order to mitigate the clinical findings, rigorous dietary Phe restriction constitutes the core of therapeutic management in PKU. Myelination is the process whereby the oligodendrocytes wrap myelin sheaths around the axons, supporting the conduction of action potentials. White matter injuries are implicated in the brain damage related to PKU, especially in untreated or poorly treated patients. The present review summarizes evidence toward putative mechanisms driving the white matter pathology in PKU patients.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.

An International survey on living kidney donation and transplant practices during the COVID-19 pandemic.

The scope of the impact of the Coronavirus disease 19 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well-defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID-19 pandemic on LDKT practices. Respondents represented 16 countries on five continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in-person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID-19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus-building are needed to guide safe reopening of LDKT programs.

Topics and Sentiments of Public Concerns Regarding COVID-19 Vaccines: Social Media Trend Analysis.

BACKGROUND: As a number of vaccines for COVID-19 are given emergency use authorization by local health agencies and are being administered in multiple countries, it is crucial to gain public trust in these vaccines to ensure herd immunity through vaccination. One way to gauge public sentiment regarding vaccines for the goal of increasing vaccination rates is by analyzing social media such as Twitter. OBJECTIVE: The goal of this research was to understand public sentiment toward COVID-19 vaccines by analyzing discussions about the vaccines on social media for a period of 60 days when the vaccines were started in the United States. Using the combination of topic detection and sentiment analysis, we identified different types of concerns regarding vaccines that were expressed by different groups of the public on social media. METHODS: To better understand public sentiment, we collected tweets for exactly 60 days starting from December 16, 2020 that contained hashtags or keywords related to COVID-19 vaccines. We detected and analyzed different topics of discussion of these tweets as well as their emotional content. Vaccine topics were identified by nonnegative matrix factorization, and emotional content was identified using the Valence Aware Dictionary and sEntiment Reasoner sentiment analysis library as well as by using sentence bidirectional encoder representations from transformer embeddings and comparing the embedding to different emotions using cosine similarity. RESULTS: After removing all duplicates and retweets, 7,948,886 tweets were collected during the 60-day time period. Topic modeling resulted in 50 topics; of those, we selected 12 topics with the highest volume of tweets for analysis. Administration and access to vaccines were some of the major concerns of the public. Additionally, we classified the tweets in each topic into 1 of the 5 emotions and found fear to be the leading emotion in the tweets, followed by joy. CONCLUSIONS: This research focused not only on negative emotions that may have led to vaccine hesitancy but also on positive emotions toward the vaccine. By identifying both positive and negative emotions, we were able to identify the public's response to the vaccines overall and to news events related to the vaccines. These results are useful for developing plans for disseminating authoritative health information and for better communication to build understanding and trust.

Peripheral polyneuropathy associated with Chikungunya virus infection.

The Chikungunya virus (CHIKV) is an arbovirus transmitted to humans through mosquito bites and can cause a series of symptoms ranging from a benign febrile illness to severe neurological conditions. We report the identification of CHIKV in a serum sample from an elderly woman with febrile illness and severe arthralgia in Brazil. The occurrence was found of peripheral polyneuropathy affecting the upper and lower limbs evidenced by electroneuromyographic findings. The patient was treated with a corticoid associated with methotrexate, suggesting that the pathophysiological basis of the case in question may be related to an immune-mediated response by T cells and inflammatory cytokines. This finding reinforces the need to be aware of the emergence of neuroinfections related to CHIKV and effective diagnoses for the early detection of neurological alterations, favoring the clinical management of these patients.

Association of single nucleotide polymorphisms in TNF-α (-308G/A and -238G/A) to dengue: Case-control and meta-analysis study.

Dengue is an acute viral disease whose clinical condition is related to the interaction of factors related to the Dengue virus (DENV), environment and the host, with the immunity of the human host contributing a substantial role in the pathogenesis of DENV infection. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes such as tumor necrosis factor (TNF-α) affect transcription and/or expression; and therefore, may influence the pathogenesis of infectious diseases, such as dengue. Consequently, the objective of this study was to assess through a case-control study whether there was an association between the presence of SNPs -308G/A and -238G/A in the TNF-α gene and 158 patients with dengue and 123 controls. No association was found between the SNPs and the dengue cases in the study population. We then performed a meta-analysis, retrieving data from case-control studies in the literature for the same polymorphisms. For SNP-308G/A, the GG genotype was associated with dengue fever (DF) risk (OR = 1.24, 1.00-1.53; p = 0.05; I2 = 0%), while the GA genotype (OR = 0.75, 0.60-0.93; p = 0.01; I2 = 0%) and allele A (OR = 0.75, 0.60-0.93; p = 0.01; I2 = 0%) were associated with protection. The genotype GG population in the Asian continent (OR = 1.81 [1.06, 3.09], p = 0.03, I2 = 0%) and American (OR = 1.29 [1.00, 1.65], p = 0.05, I2 = 0%) was also associated with protection in the comparison between the cases versus the control group. In each comparison, the dominant model AA + GA (p < 0.00001) conferred protection. For SNP-238G/A the GA genotype was associated with risk for dengue hemorrhagic fever (DHF; OR = 2.17, 1.28-3.67; p = 0.004; I2 = 0%)), and the dominant AA + GA model (p < 0.00001) was associated with protection in each comparison. In summary, our results did not associate SNPs in the TNF-α gene to dengue in the Brazilian northeast population. However, combined literature data suggested the effect of the GG and GA genotypes of the SNP-308G/A on risk and protection, respectively, in Asian and American populations.

Effects of omega-3 fatty acids supplementation on inflammatory parameters after chronic administration of L-tyrosine.

Tyrosinemia type II is an autosomal recessive inborn error of metabolism caused by hepatic cytosolic tyrosine aminotransferase deficiency. Importantly, this disease is associated with neurological and developmental abnormalities in many patients. Considering that the mechanisms underlying neurological dysfunction in hypertyrosinemic patients are poorly understood, in the present work we investigated the levels of cytokines - tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-10 - in cerebellum, hippocampus, striatum of young rats exposed to chronic administration of L-tyrosine. In addition, we also investigated the impact of the supplementation with Omega-3 fatty acids (n-3 PUFA) on the rodent model of Tyrosinemia. Notably, previous study demonstrated an association between L-tyrosine toxicity and n-3 PUFA deficiency. Our results showed a significant increase in the levels of pro- and anti-inflammatory cytokines in brain structures when animals were administered with L-tyrosine. Cerebral cortex and striatum seem to be more susceptible to the inflammation induced by tyrosine toxicity. Importantly, n-3 PUFA supplementation attenuated the alterations on cytokines levels induced by tyrosine exposure in brain regions of infant rats. In conclusion, the brain inflammation is also an important process related to tyrosine neurotoxicity observed in the experimental model of Tyrosinemia. Finally, n-3 PUFA supplementation could be considered as a potential neuroprotective adjunctive therapy for Tyrosinemias, especially type II.

Oral Rehabilitation With Dental Implants and the Importance of a Preventive Evaluation for Osteonecrosis of the Jaws Associated With Medications.

Osteonecrosis of the jaw is a possible oral complication resulting from antiresorptive therapies, such as bisphosphonates (Bfs). Although the etiology is not entirely clear, it has been shown to be dependent on several factors, with the traumatic stimulation caused by the placement of teeth implants indicated as one of the predisposing factors to this pathology. The indications and preventive methods for performing these procedures have been questioned, making it essential to determine the proper protocols. Thus, the present study aims to discuss the risks of the development of osteonecrosis in patients undergoing dental implant surgery who use Bfs as well as to discuss related local and systemic factors and possible methods for preventing this side effect. The study also aims to present a clinical case of an osteopenic patient who used Bfs and underwent rehabilitation through implants according to specific protocols, which resulted in successful treatment.

Fundamentals of CNS energy metabolism and alterations in lysosomal storage diseases.

The brain has a very high requirement for energy. Adult brain relies on glucose as an energy substrate, whereas developing brain can utilize alternative substrates as well as glucose for energy and for the biosynthesis of lipids and proteins required for brain development. Metabolism provides the energy required to support all cellular functions and brain development and building blocks for macromolecules. Lysosomes are organelles involved in breakdown of biological compounds including proteins and complex lipids in the body and brain. Recent studies suggest that lysosomal dysfunction can damage neurons and/or alter neurotransmitter homeostasis. Several studies also implicate mitochondrial dysfunction in the pathophysiology of brain damage in lysosomal storage diseases. This manuscript provides a brief review of energy metabolism and the key pathways involved in metabolism in brain. Roles of lysosomes related to metabolism and neurotransmission are discussed, and evidence for mitochondrial dysfunction in several lysosomal storage diseases is presented. This article is part of the Special Issue "Lysosomal Storage Disorders".

Does Intradialytic Exercise Improve Removal of Solutes by Hemodialysis? A Systematic Review and Meta-analysis.

OBJECTIVE: To describe a systematic review and meta-analysis to identify if intradialytic exercise improves the removal of solutes and the hemodialysis adequacy. DATA SOURCES: A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed. The sources were MEDLINE (via PubMed), Web of Science, LILACS, and SciELO, from inception until July 2018. STUDY SELECTION: Clinical trials including patients on chronic hemodialysis submitted to the intervention of aerobic intradialytic exercise. DATA EXTRACTION: Evaluating as outcomes the removal of solutes (creatinine, phosphate, potassium) and/or adequacy parameters (Kt/V-urea). DATA SYNTHESIS: The systematic review included 23 studies (7 evaluating the effect of 1 exercise session and 16 evaluating the effect of training, lasting from 6 to 25 weeks). Eleven RCT were included in the meta-analyses. It was observed that the aerobic intradialytic exercise increased the Kt/V-urea (0.15; 95% confidence interval [95% CI], 0.08-0.21) and decreased creatinine (-1.82 mg/dL; 95% CI, -2.50 to -1.13), despite the high heterogeneity of the analysis. No differences were found in phosphorus and potassium removal. CONCLUSION: The aerobic intradialytic exercise may be suggested to improve the Kt/V-urea and the creatinine removal during the dialysis.

The "Hypertension Approaches in the Elderly: a Lifestyle study" multicenter, randomized trial (HAEL Study): rationale and methodological protocol.

BACKGROUND: Hypertension is a clinical condition highly prevalent in the elderly, imposing great risks to cardiovascular diseases and loss of quality of life. Current guidelines emphasize the importance of nonpharmacological strategies as a first-line approach to lower blood pressure. Exercise is an efficient lifestyle tool that can benefit a myriad of health-related outcomes, including blood pressure control, in older adults. We herein report the protocol of the HAEL Study, which aims to evaluate the efficacy of a pragmatic combined exercise training compared with a health education program on ambulatory blood pressure and other health-related outcomes in older individuals. METHODS: Randomized, single-blinded, multicenter, two-arm, parallel, superiority trial. A total of 184 subjects (92/center), ≥60 years of age, with no recent history of cardiovascular events, will be randomized on a 1:1 ratio to 12-week interventions consisting either of a combined exercise (aerobic and strength) training, three times per week, or an active-control group receiving health education intervention, once a week. Ambulatory (primary outcome) and office blood pressures, cardiorespiratory fitness and endothelial function, together with quality of life, functional fitness and autonomic control will be measured in before and after intervention. DISCUSSION: Our conceptual hypothesis is that combined training intervention will reduce ambulatory blood pressure in comparison with health education group. Using a superiority framework, analysis plan prespecifies an intention-to-treat approach, per protocol criteria, subgroups analysis, and handling of missing data. The trial is recruiting since September 2017. Finally, this study was designed to adhere to data sharing practices. TRIAL REGISTRATION: NCT03264443 . Registered on 29 August, 2017.

Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats.

Deficiency of hepatic enzyme tyrosine aminotransferase characterizes the innate error of autosomal recessive disease Tyrosinemia Type II. Patients may develop neurological and developmental difficulties due to high levels of the amino acid tyrosine in the body. Mechanisms underlying the neurological dysfunction in patients are poorly known. Importantly, Tyrosinemia patients have deficient Omega-3 fatty acids (n-3 PUFA). Here, we investigated the possible neuroprotective effect of the treatment with n-3 PUFA in the alterations caused by chronic administration of L-tyrosine on important parameters of energetic metabolism and oxidative stress in the hippocampus, striatum and cerebral cortex of developing rats. Chronic administration of L-tyrosine causes a decrease in the citrate synthase (CS) activity in the hippocampus and cerebral cortex, as well as in the succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) activities, and an increase in the α-ketoglutarate dehydrogenase activity in the hippocampus. Moreover, in the striatum, L-tyrosine administration caused a decrease in the activities of CS, SDH, creatine kinase, and complexes I, II-III and IV of the mitochondrial respiratory chain. We also observed that the high levels of L-tyrosine are related to oxidative stress in the brain. Notably, supplementation of n-3 PUFA prevented the majority of the modifications caused by the chronic administration of L-tyrosine in the cerebral enzyme activities, as well as ameliorated the oxidative stress in the brain regions of rats. These results indicate a possible neuroprotective and antioxidant role for n-3 PUFA and may represent a new therapeutic approach and potential adjuvant therapy to Tyrosinemia Type II individuals.

Assessment of Valeriana officinalis l. (Valerian) for Conscious Sedation of Patients During the Extraction of Impacted Mandibular Third Molars: A Randomized, Split-Mouth, Double-Blind, Crossover Study.

PURPOSE: The objective of the present study was to evaluate the effectiveness of an herbal drug (valerian) to control anxiety during mandibular third molar extraction compared with a reference benzodiazepine drug commonly used in dental procedures (midazolam). MATERIALS AND METHODS: Twenty anxious patients with an indication for bilateral extraction of mandibular third molars were selected. The patients received capsules containing valerian 100 mg or midazolam 15 mg orally 60 minutes before the procedures in a randomized, split-mouth, crossover design. Changes in the physiological parameters (eg, oxygen saturation, heart rate, blood pressure, respiratory rate) were assessed at specific times during surgery, and the patients completed a questionnaire postoperatively. The data were analyzed using the Wilcoxon and paired t tests, with a significance level of 5%. RESULTS: No statistically significant differences in oxygen saturation were observed, regardless of the drug used. However, the other physiological parameters were significantly lower when the patients had taken midazolam compared with valerian. Somnolence was the most common side effect reported with both drugs. CONCLUSIONS: Although midazolam was more effective in reducing the physiological parameters studied, valerian seemed to provide the comfort and relaxation required, with no sedation and less somnolence than midazolam, during third molar extraction. Further studies are necessary before valerian can be clinically recommended.