RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases. AIM OF THE STUDY: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol. MATERIAL AND METHODS: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model. RESULTS: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg). CONCLUSION: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.

Asunto(s)

Monoterpenos Acíclicos , Analgésicos , Antiinflamatorios , Edema , Lippia , Aceites Volátiles , Hojas de la Planta , Animales , Lippia/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Brasil , Analgésicos/farmacología , Analgésicos/aislamiento & purificación , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Masculino , Hojas de la Planta/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Monoterpenos Acíclicos/farmacología , Plantas Medicinales/química , Dolor/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Dimensión del Dolor/efectos de los fármacos

RESUMEN

Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. To date, there is no specific treatment established for sepsis. In the extracellular compartment, purines such as adenosine triphosphate (ATP) and adenosine play essential roles in the immune/inflammatory responses during sepsis and septic shock. The balance of extracellular levels among ATP and adenosine is intimately involved in the signals related to immune stimulation/immunosuppression balance. Specialized enzymes, including CD39, CD73, and adenosine deaminase (ADA), are responsible to metabolize ATP to adenosine which will further sensitize the P2 and P1 purinoceptors, respectively. Disruption of the purinergic pathway had been described in the sepsis pathophysiology. Although purinergic signaling has been suggested as a potential target for sepsis treatment, the majority of data available were obtained using pre-clinical approaches. We hypothesized that, as a reflection of deregulation on purinergic signaling, septic patients exhibit differential measurements of serum, neutrophils and monocytes purinergic pathway markers when compared to two types of controls (healthy and ward). It was observed that ATP and ADP serum levels were increased in septic patients, as well as the A2a mRNA expression in neutrophils and monocytes. Both ATPase/ADPase activities were increased during sepsis. Serum ATP and ADP levels, and both ATPase and ADPase activities were associated with the diagnosis of sepsis, representing potential biomarkers candidates. In conclusion, our results advance the translation of purinergic signaling from pre-clinical models into the clinical setting opening opportunities for so much needed new strategies for sepsis and septic shock diagnostics and treatment.

Asunto(s)

Sepsis , Choque Séptico , Humanos , Apirasa/metabolismo , Adenosina , Adenosina Trifosfato/metabolismo , Biomarcadores , Sepsis/diagnóstico , Adenosina Difosfato , Adenosina Trifosfatasas

RESUMEN

INTRODUCTION AND OBJECTIVES: This study aimed to evaluate the role of two widely distributed natural phenolic compounds, gallic acid (GA) and methyl gallate (MG), in an in vitro model of urolithiasis, by using the methodology of calcium oxalate (CaOx) crystals formation, which is the most common type of urinary or kidney stones. MATERIAL AND METHODS: The compounds GA and MG were subjected to anti-crystallization activities in different concentrations (0.003-0.03 mg/mL), and the quantity and morphology of crystals were determined by microscopy after 60 min. RESULTS: GA inhibited about 44-57% of the total CaOx crystals formation, while MG inhibited about 48.35%, when compared to vehicle-exposed samples (distilled water; negative control group). GA and MG exposure inhibited monohydrate type calculi formation, which is considered the most common and harmful crystal category. The compounds also decreased absorbance, which in turn is related to reduced CaOx aggregation and precipitation. CONCLUSIONS: Altogether, this study shows, for the first time, that GA and MG are promising compounds with antiurolithiatic properties, opening new perspectives for future in vivo evaluations of the potential of these compounds in the treatment and/or prevention of urinary or kidney stones.

Asunto(s)

Cálculos Renales , Urolitiasis , Oxalato de Calcio , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Humanos , Urolitiasis/tratamiento farmacológico

RESUMEN

INTRODUCTION AND OBJECTIVES: This study aimed to evaluate the role of 2 widely distributed natural phenolic compounds, gallic acid (GA) and methyl gallate (MG), in an in vitro model of urolithiasis, by using the methodology of calcium oxalate crystals formation, which is the most common type of urinary or kidney stones. MATERIAL AND METHODS: The compounds GA and MG were subjected to anti-crystallization activities in different concentrations (0.003-0.03mg/mL), and the quantity and morphology of crystals were determined by microscopy after 60min. RESULTS: GA inhibited about 44-57% of the total calcium oxalate crystals formation, while MG inhibited about 48.35%, when compared to vehicle-exposed samples (distilled water; negative control group). GA and MG exposure inhibited monohydrate type calculi formation, which is considered the most common and harmful crystal category. The compounds also decreased absorbance, which in turn is related to reduced calcium oxalate crystals aggregation and precipitation. CONCLUSIONS: Altogether, this study shows, for the first time, that GA and MG are promising compounds with antiurolithiatic properties, opening new perspectives for future in vivo evaluations of the potential of these compounds in the treatment and/or prevention of urinary or kidney stones.

RESUMEN

Glioblastoma (GB) is the most common and aggressive form of primary brain tumor, in which the presence of an inflammatory environment, composed mainly by tumor-associated macrophages (TAMs), is related to its progression and development of chemoresistance. Toll-Like Receptors (TLRs) are key components of the innate immune system and their expression in both tumor and immune-associated cells may impact the cell communication in the tumor microenvironment (TME), further modeling cancer growth and response to therapy. Here, we investigated the participation of TLR4-mediated signaling as a mechanism of induced-immune escape in GB. Initially, bioinformatics analysis of public datasets revealed that TLR4 expression is lower in GB tumors when compared to astrocytomas (AST), and in a subset of TAMs. Further, we confirmed that TLR4 expression is downregulated in chemoresistant GB, as well as in macrophages co-cultured with GB cells. Additionally, TLR4 function is impaired in those cells even following stimulation with LPS, an agonist of TLR4. Finally, experiments performed in a cohort of clinical primary and metastatic brain tumors indicated that the immunostaining of TLR4 and CD45 are inversely proportional, and confirmed the low TLR4 expression in GBs. Interestingly, the cytoplasmic/nuclear pattern of TLR4 staining in cancer tissues suggests additional roles of this receptor in carcinogenesis. Overall, our data suggest the downregulation of TLR4 expression and activity as a strategy for GB-associated immune escape. Additional studies are necessary to better understand TLR4 signaling in TME in order to improve the benefits of immunotherapy based on TLR signaling.

Asunto(s)

Neoplasias Encefálicas/inmunología , Regulación hacia Abajo/inmunología , Glioblastoma/inmunología , Glioblastoma/metabolismo , Evasión Inmune/inmunología , Receptor Toll-Like 4/inmunología , Macrófagos Asociados a Tumores/inmunología , Anciano , Animales , Neoplasias Encefálicas/metabolismo , Línea Celular , Línea Celular Tumoral , Proliferación Celular/fisiología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Transducción de Señal/inmunología , Receptor Toll-Like 4/metabolismo , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/metabolismo

RESUMEN

BACKGROUND: The preemptive use of anti-inflammatory drugs, such as corticosteroids and NSAIDs, has the potential to reduce pain, swelling and trismus following oral surgery. The aim of this study was to compare the efficacy of dexamethasone and ketorolac tromethamine in reducing pain, swelling and trismus after mandibular third molar removal. MATERIAL AND METHODS: The researches implemented a triple-blind, randomized clinical trial. The study was conducted with ASA I individuals aging between 18 and 35 years, which were randomized and submitted to two interventions, one with 8mg dexamethasone and the other with 20mg ketorolac tromethamine given 1h before the procedure. The primary predictor variable was the use of dexamethasone or ketorolac. The primary outcome variable was the postoperative pain level, measured with a Visual Analogue Scale. The secondary outcome variables were the amount of rescue analgesic consumed, swelling and trismus. Repeated-measures ANOVA and t-test for paired samples were used to compare the means. Significance was set at p < 0.05. RESULTS: Fifty individuals were randomized and allocated to intervention, and the sample was composed of 40 subjects who completed the study (27 female and 13 male). Dexamethasone, when compared to ketorolac tromethamine, showed a significantly higher reduction in pain level at 8h, 16h, 24h, 32h, 40h and 72h, in swelling and trismus at 24h, 48h, 72h and 7 days and in total number of rescue analgesics taken up to 72h postoperative (p < 0.05). CONCLUSIONS: The clinical performance of dexamethasone in controlling pain, swelling and trismus after mandibular third molar removal was superior to ketorolac tromethamine's.

Asunto(s)

Ketorolaco , Diente Impactado , Dexametasona/uso terapéutico , Método Doble Ciego , Edema/etiología , Edema/prevención & control , Femenino , Humanos , Masculino , Tercer Molar/cirugía , Dolor Postoperatorio/prevención & control , Extracción Dental/efectos adversos , Diente Impactado/cirugía , Trismo/etiología , Trismo/prevención & control

RESUMEN

OBJECTIVE: The study aimed to review and report the current evidence supporting the use of mouthwashes as a preprocedural protocol on dental offices. MATERIALS AND METHODS: This study is a secondary one that performed a comprehensive literature search of scientific studies published up to 10th August 2020 in PubMed, Scopus, Web of Science, and Scientific Electronic Library Online (Scielo) databases. The electronic search strategy was performed using free text and DeCS/MeSH terms. RESULTS: Only five studies were included in this work, despite 140 studies that were identified with the research strategy. In vivo studies were carried out in two works, in vitro studies were described in two papers, and a in silico approach was used in one work. No cetylpyridinium chloride studies were identified, while chlorhexidine and povidone studies were more studied. CONCLUSIONS: There is reduced evidence about how preprocedural mouthwashes decrease SARS-CoV-2 salivary load.

Asunto(s)

COVID-19/prevención & control , Atención Odontológica/métodos , Antisépticos Bucales/farmacología , Antisépticos Bucales/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Humanos , Carga Viral/efectos de los fármacos

RESUMEN

BACKGROUND: Although there are no population-based studies that support an association, there are reports in the literature of mucocutaneous, vesiculobullous and ulcerated lesions in the oral mucosa in cases of arbovirus infection. The aim of this study is to analyze the prevalence of ulcerative stomatitis in individuals affected by arboviruses in a population of the municipality of Arcoverde, Pernambuco, Brazil. MATERIAL AND METHODS: 1,003 people living in an area assigned to a Primary Health Care Unit were interviewed. A structured questionnaire was used for data collection, with questions about sociodemographic variables, residence conditions, general health information, as well as information about the general signs and symptoms of arboviruses and specifically about oral lesions. RESULTS: Of the 1,003 individuals interviewed, 815 (81.25%) were infected by one or more arboviruses. Of these, 147 (18%) reported ulcerated oral lesions during arbovirus infections. The association between arbovirus infections and the presence of ulcerated oral lesions was statistically significant (p = 0.000). CONCLUSIONS: In these cases, the ulcerated lesions on the oral mucosa appear to be associated with arbovirus infection, especially Chikungunya, although the pathophysiological mechanisms are not defined, and the studies are not sufficient to confirm this association.

Asunto(s)

Infecciones por Arbovirus , Arbovirus , Fiebre Chikungunya , Infecciones por Arbovirus/epidemiología , Brasil/epidemiología , Humanos , Prevalencia

RESUMEN

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.

Asunto(s)

Antituberculosos/uso terapéutico , Oxadiazoles/uso terapéutico , Tuberculosis/tratamiento farmacológico , Animales , Antituberculosos/farmacología , Antituberculosos/toxicidad , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana , Femenino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Pruebas de Mutagenicidad , Mycobacterium tuberculosis/efectos de los fármacos , Oxadiazoles/farmacología , Oxadiazoles/toxicidad , Tuberculosis/microbiología

RESUMEN

PURPOSE: To analyze pain scores after surgery in a group of patients submitted to inguinal hernia repair under peripheral nerve block with local or spinal anesthesia. METHODS: Fifty patients were divided into two groups (both with 25 patients each). In the first group the patients were submitted to herniorrhaphy under peripheral block and local anesthesia (LG) and in the other group the patients were submitted to the same procedure under spinal anesthesia (RG). The pain was assessed using the international visual analog pain scale at four different moments. The analysis cost of the procedure was performed using the hospital's average final cost, without including medical expenses. RESULTS: The groups were homogeneous in relation to the epidemiological and clinical features. There was no significant difference between the pain in the intraoperative period and in the return visit for both groups (p = 0.17 and p = 0.18). In the immediate postoperative period, both groups reported no pain at all. In general, the RG reported a greater pain score (16% for RG and 12% for LG). Complications were more frequent in patients submitted to spinal anesthesia (40% versus 8%) (p = 0.008). The surgical time was higher in the LG (39.3 ± 9.2 min) versus (28.7 ± 7.5 min) (p = 0.01). The average final cost of the procedure was US$ 100.98 for the LG and US$ 166.19 for the RG (p = 0.00). CONCLUSION: The inguinal hernioplastia under local anesthesia plus sedation is a safe method, with a low incidence of complications, great acceptance by patients and less expensive.

Asunto(s)

Anestesia Local , Anestesia Raquidea , Hernia Inguinal/cirugía , Herniorrafia , Bloqueo Nervioso , Dolor Postoperatorio/prevención & control , Adulto , Anciano , Sedación Consciente , Femenino , Ingle/cirugía , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Periodo Posoperatorio

RESUMEN

BACKGROUND: This study estimated the inter-rater reliability and agreement of the somatosensory assessment performed at masseter and temporomandibular joint (TMJ) region in a group of healthy female and male participants. METHODS: Forty healthy participants (20 men and 20 women) were evaluated in two sessions by two different examiners. Cold detection threshold (CDT), warm detection threshold (WDT), thermal sensory limen (TSL), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind-up ratio (WUR) and pressure pain threshold (PPT) were assessed on the skin overlying TMJ and masseter body. Mixed ANOVA, intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were applied to the data (α = 5%). Nonoverlapping 95% confidence intervals (95% CI) of ICCs were considered significantly different. RESULTS: The ICCs of 77% of all quantitative sensory testing (QST) measurements were considered fair to excellent (ICCs: 0.47-0.97), and WUR presented the lowest values. The reliability of WDT, TSL and HPT of masseter was significantly higher than TMJ, whereas the MDT reliability of TMJ was higher than masseter. In addition, the following combination of test/sites presented significantly lower ICCs for women: HPT, MDT of TMJ and MPT of both TMJ and masseter. Finally, the highest SEM values were presented for CPT and MPT. CONCLUSION: The overall somatosensory assessment of the masticatory structures performed by two examiners can be considered sufficiently reliable to discriminate participants, except WUR. Possible site and sex influences on the reproducibility parameters should be taken into account for an appropriate interpretation and clinical application of QST. SIGNIFICANCE: The test site and participant's sex can significantly influence the relative reliability and agreement of quantitative sensory testing applied to musculoskeletal orofacial region, which affect the capacity to discriminate participants and to evaluate changes over time.

Asunto(s)

Calor , Músculo Masetero/fisiología , Umbral del Dolor/fisiología , Presión , Articulación Temporomandibular/fisiología , Sensación Térmica/fisiología , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Dolor , Dimensión del Dolor , Reproducibilidad de los Resultados , Umbral Sensorial/fisiología , Factores Sexuales , Piel , Adulto Joven

RESUMEN

Facial-onset sensory and motor neuronopathy (FOSMN) syndrome represents a rare, slowly progressive, lower motor neuron disease with sensory compromise, involving mainly the face, bulbar region and upper limbs. However, non-motor symptoms and neurogenetic studies have rarely been evaluated in large case series. In the present study, 10 unrelated Brazilian patients with FOSMN syndrome underwent extensive clinical, laboratory, neurophysiological and neurogenetic assessment. Median age at symptom onset was 52.1 years, and men and women were equally affected. Patients presented with hemifacial or bilateral facial paresthesia and weakness, which evolved with dysphagia, dysphonia, and facial and tongue atrophy and, finally, a dropped-head, upper limb weakness and syringomyelia-like sensory disturbances in the upper limbs. All 10 patients showed chronic diffuse neurogenic compromise of bulbar, cervical and thoracic myotomes, and abnormal blink reflex tests. A positive family history of neurodegeneration was identified in six cases, and revealed pathogenic gene variants in three families (involving VCP, TARDBP and CHCHD10). Thus, our case series has revealed new findings regarding FOSMN syndrome: (i) its clinical course is not always benign, with poorer prognoses associated with dropped-head syndrome and early bulbar compromise; (ii) FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; and (iii) a definite genetic basis may be observed in some cases.

Asunto(s)

Enfermedades del Nervio Facial/fisiopatología , Enfermedad de la Neurona Motora/fisiopatología , Adulto , Edad de Inicio , Anciano , Parpadeo , Brasil , Enfermedades del Nervio Facial/diagnóstico por imagen , Enfermedades del Nervio Facial/genética , Femenino , Pruebas Genéticas , Trastornos Heredodegenerativos del Sistema Nervioso/epidemiología , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/genética , Debilidad Muscular/etiología , Atrofia Muscular Espinal/epidemiología , Neuroimagen , Examen Neurológico , Parestesia/etiología

RESUMEN

Sepsis is a life-threatening condition with high mortality rates that is caused by dysregulation of the host response to infection. We previously showed that treatment with the cannabinoid CB1 receptor antagonist rimonabant reduced mortality rates in animals with sepsis that was induced by cecal ligation and puncture (CLP). This improvement in the survival rate appeared to be related to an increase in arginine vasopressin (AVP) levels 12 h after CLP. The present study investigated the effects of rimonabant on organ dysfunction, hematologic parameters, and vascular reactivity in male Wistar rats with sepsis induced by CLP. Intraperitoneal treatment with rimonabant (10 mg/kg, 4 h after CLP) abolished the increase in the plasma levels of lactate, lactate dehydrogenase, glucose, and creatinine kinase MB without altering hematological parameters (i.e., leukopenia and a reduction of platelet counts). CLP increased plasma levels of nitrate/nitrite (NOx) and induced vasoconstriction in the tail artery. The treatment of CLP rats with rimonabant did not alter NOx production but reduced the vasoconstriction. Rimonabant also attenuated the hyperreactivity to AVP induced by CLP without affecting hyporesponsiveness to phenylephrine in aortic rings. These results suggest that rimonabant reduces organ dysfunction during sepsis, and this effect may be related to AVP signaling in blood vessels. This effect may have contributed to the higher survival rate in rimonabant-treated septic animals.

Asunto(s)

Aorta/fisiopatología , Insuficiencia Multiorgánica/dietoterapia , Rimonabant/farmacología , Sepsis/fisiopatología , Vasoconstricción/efectos de los fármacos , Animales , Arginina Vasopresina/metabolismo , Antagonistas de Receptores de Cannabinoides/farmacología , Antagonistas de Receptores de Cannabinoides/uso terapéutico , Ciego/lesiones , Hemodinámica/efectos de los fármacos , Masculino , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Rimonabant/uso terapéutico , Transducción de Señal , Tasa de Supervivencia

RESUMEN

INTRODUCTION: Organ transplantation is often the only possible treatment to save the lives of patients with end-stage organ failure. Limiting factors include failure to notify in cases of patients with brain death, the inefficient procurement and distribution of organs, the lack of specific educational policies for health care professionals, lack of knowledge on the organ transplantation process, and family refusal for organ donation. OBJECTIVE: To evaluate the knowledge of students enrolled in different undergraduate university courses in Rio de Janeiro on the regulations and strategies governing transplant organ donation in Brazil. METHODS: This qualitative, observational study used a 10-item questionnaire aimed at obtaining data on respondents' general knowledge regarding organ donation and transplantation. The questionnaire was applied using either a printed or an electronic version developed on Google Forms and was completed anonymously. RESULTS: Overall, 587 questionnaires were completed. The participants were divided into 3 groups according to their field of study: 256 (43.6%) from courses related to arts and humanities, 159 (27.1%) from science and technology-related courses, and 172 (29.3%) from the biomedical field. Most respondents (396; 67.5%) were unaware of the criteria required to be an organ transplant donor. CONCLUSION: There is a significant lack of knowledge among university students on issues related to the organ donation and transplantation process in Brazil.

Asunto(s)

Conocimientos, Actitudes y Práctica en Salud , Donantes de Tejidos/psicología , Obtención de Tejidos y Órganos , Adulto , Brasil , Femenino , Humanos , Masculino , Estudiantes/psicología , Encuestas y Cuestionarios , Donantes de Tejidos/provisión & distribución , Universidades

RESUMEN

AIMS: To screen 20 micro-organisms for ω-transaminase (ω-TA) activity by the kinetic resolution of rac-1-phenylethylamine, followed by testing rac-amines of pharmaceutical interest with bulky substituents and to conduct the asymmetric synthesis of a chiral amine. METHODS AND RESULTS: Stemphylium lycopersici was selected as the best biocatalyst. By the central composite rotatable design (CCRD), it was found that, at lower pH (5·5 and 6·5), the lyophilized micro-organism biocatalysed the kinetic resolution of rac-1-phenylethylamine with 99% enantiomeric excess (e.e.) ((R)-enantiomer) with acetophenone conversions ranged from 41 to 45%. Interestingly, the lyophilized crude enzymatic extract lead to better results at pH from 7·0 to 9·0, with conversions up to 47% and about 99% e.e. We also attested that as much as higher is the pyruvate (amino acceptor) concentration, higher is the acetophenone conversion, corroborating the presence of ω-TA-type enzymes. Among different sterically hindered racemic amines tested, rac-1,2,3,4-tetrahydro-1-naphthylamine and rac-phenylbutylamine were satisfactorily kinetically resolved in up to 91% e.e. (R). The results for the asymmetric synthesis showed excellent conversion (>85%) for the S-1-phenylethylamine, indicating (S)-stereopreference. CONCLUSION: Stemphylium lycopersici showed to be an important tool for broader substrate scope transaminases and a relevant player on the development of new biocatalysts with ability in asymmetric synthesis reactions. SIGNIFICANCE AND IMPACT OF THE STUDY: Here in, we contribute to the improvement of the biocatalytic toolbox for chiral amines synthesis. Interestingly, we have found that the crude enzymatic extract of the endophytic fungus S. lycopersici could accept bulky substrates with reasonable activity, compared to the wild-type transaminase already published over literature, and with high enantioselectivity.

Asunto(s)

Aminas/química , Aminas/metabolismo , Ascomicetos/enzimología , Acetofenonas/metabolismo , Biocatálisis , Biotransformación , Cinética , Fenetilaminas/química , Fenetilaminas/metabolismo , Estereoisomerismo , Transaminasas/metabolismo

RESUMEN

Inherited neurometabolic disorders represent a growing group of inborn errors of metabolism that present with major neurological symptoms or a complex spectrum of symptoms dominated by central or peripheral nervous system dysfunction. Many neurological presentations may arise from the same metabolic defect, especially in autosomal-recessive inherited disorders. Motor neuron disease (MND), mainly represented by amyotrophic lateral sclerosis, may also result from various inborn errors of metabolism, some of which may represent potentially treatable conditions, thereby emphasizing the importance of recognizing such diseases. The present review discusses the most important neurometabolic disorders presenting with motor neuron (lower and/or upper) dysfunction as the key clinical and neuropathological feature.

Asunto(s)

Encefalopatías Metabólicas Innatas/complicaciones , Encefalopatías Metabólicas Innatas/genética , Enfermedad de la Neurona Motora/etiología , Enfermedad de la Neurona Motora/genética , Esclerosis Amiotrófica Lateral/genética , Humanos

RESUMEN

In this paper we show a very simple route for the incorporation of catalytically active niobium species on the surface of carbon materials, such as graphene oxide, carbon nanotubes and activated carbon. Some existing methods of incorporating a transition metal on a support have involved co-precipitation or wet impregnation, to obtain the corresponding oxides. These methods, however, cause reduction in the specific area of the support and can also form large metal oxide particles with loss of metal exposure. Therefore, here we present a novel way to add catalytically active species on the surfaces of different types of carbon through the formation of interaction complexes between the metal precursor and the functional groups of the carbon matrix. Because of the excellent catalytic properties exhibited by the niobium species we choose the NH4[NbO(C2O4)2(H2O)2]·2H2O salt as the model precursor. The characterization by XPS reveals the presence of the niobium species indicated by the displacement of the peaks between 206-212 eV related to the oxalate species according to the spectrum from pure niobium oxalate. Images obtained by TEM and SEM show the typical morphologies of carbonaceous materials without the niobium oxide formation signal, which indicates the presence of niobium complexes as isolated sites on the carbon surfaces. This new class of materials exhibited excellent properties as catalysts for pollutant oxidation. The presence of Nb promotes the catalytic activation of H2O2 generating hydroxyl radicals in situ, which allows their use in the organic compound oxidation processes. Tests for DBT oxidation indicate that Nb significantly improves the removal of such pollutants in biphasic reactions with removal around 90% under the tested conditions. Theoretical calculations showed that the most favorable adsorption model is an ionic complex presenting a ΔG = -108.7 kcal mol(-1) for the whole adsorption process.

RESUMEN

Polymorphisms in interleukin (IL)-18, IL-12 and interferon (IFN)-γ genes are associated with different levels of cytokines expression and have been associated with rheumatoid arthritis (RA). IL-18 +105 A/C, IL-12B +1188 A/C and IFN-γ +874 T/A polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (PCR) and amplification refractory mutation system PCR from 90 RA patients and 186 healthy individuals. There were significant differences to IL-18 +105 A/C polymorphism between the RA and control groups (odds ratio = 3.77; P < 0.0001). Individual carriers of the variant allele C had a 3.77-fold increased risk of for RA (P = 0.0032). No association was observed for IL-12B and IFN-γ polymorphisms. Our finds suggest a possible role for IL-18 polymorphism in the RA susceptibility in studied population.

Asunto(s)

Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Interferón gamma/genética , Subunidad p40 de la Interleucina-12/genética , Interleucina-18/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Brasil , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Humanos , Interferón gamma/inmunología , Subunidad p40 de la Interleucina-12/inmunología , Interleucina-18/inmunología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Riesgo

RESUMEN

INTRODUCTION: A few days after implantation, the embryo grows intensely and trophoblast giant cells (TGC) undergo cell rearrangement, especially of their cytoskeleton. Although we previously showed vimentin in mouse antimesometrial TGC at embryonic days (E) 8.5-10.5, by immunostaining, we did not demonstrate what is the first embryonic day that TGC synthesize vimentin and whether mouse chorioallantoic placental TGC express vimentin. This is of particular interest because cytokeratin is a marker for TGC in the placenta. METHODS: We performed in situ hybridization and immunolocalization, combined with histological and stereological techniques, to study vimentin expression between E6.5 and E12.5 and we investigated Vegf and Flt1/Vegfr1 expression in TGC. RESULTS: Analyses of morphologic parameters of TGC showed that the highest expansion of nuclear and cytoplasmic volumes (p ≤ 0.05) occurred at E7.5. We detected vimentin expression in TGC from E7.5 onwards; vimentin disappeared as TGC degeneration advanced. Primary and secondary TGC showed intense positive immunostaining for vimentin, Vegf and Flt1/Vegfr1 at E7.5. In the chorioallantoic placenta, parietal TGC (zone of giant cells), spiral artery-associated TGC, maternal blood canal-associated TGC and TGC within the sinusoidal spaces of the labyrinth exhibited an intense immunopositive-reaction for vimentin. DISCUSSION: At E7.5 TGC acquire vimentin, Vegf and Flt1/Vegfr1; at the same time, blood begins to drain from maternal vessels. Vimentin synthesis initiates during a differentiation process of TGC and continues throughout the stage of vascular TGC. CONCLUSIONS: We propose that vimentin is a characteristic factor of specialized (vascular) TGC, being a valuable tool for studying pathological pregnancies associated with defects in vascular trophoblasts in mice.

Asunto(s)

Células Gigantes/metabolismo , Trofoblastos/metabolismo , Vimentina/biosíntesis , Animales , Implantación del Embrión , Femenino , Edad Gestacional , Inmunohistoquímica , Hibridación in Situ , Ratones , Placenta/irrigación sanguínea , Placenta/citología , Embarazo , Trofoblastos/citología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/biosíntesis

RESUMEN

The observation that the fluidity must remain within a critical interval, outside which the stability and functionality of the cell tends to decrease, shows that stability, fluidity and function are related and that the measure of erythrocyte stability allows inferences about the fluidity or functionality of these cells. This study determined the biochemical and hematological variables that are directly or indirectly related to erythrocyte stability in a population of 71 volunteers. Data were evaluated by bivariate and multivariate analysis. The erythrocyte stability showed a greater association with hematological variables than the biochemical variables. The RDW stands out for its strong correlation with the stability of erythrocyte membrane, without being heavily influenced by other factors. Regarding the biochemical variables, the erythrocyte stability was more sensitive to LDL-C. Erythrocyte stability was significantly associated with RDW and LDL-C. Thus, the level of LDL-C is a consistent link between stability and functionality, suggesting that a measure of stability could be more one indirect parameter for assessing the risk of degenerative processes associated with high levels of LDL-C.

Asunto(s)

Membrana Eritrocítica/metabolismo , Hematología , Lípidos/sangre , Fluidez de la Membrana , Humanos , Persona de Mediana Edad , Análisis Multivariante