Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Complementary Therapies and Their Association with Problems in Therapeutic Adherence to Conventional Synthetic DMARDs in Rheumatoid Arthritis: A Cross-Sectional Study.

The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.

High-Resolution Mass Spectrometry Identification and Characterization of Flavonoids from Fridericia chica Leaves Extract with Anti-Arbovirus Activity.

Plant extracts are complex mixtures that are difficult to characterize, and mass spectrometry is one of the main techniques currently used in dereplication processes. Fridericia chica is a species with medicinal uses in Latin American countries, used in the treatment of inflammatory and infectious diseases. Extracts of this plant species are characterized by the presence of anthocyanidins. In this study, using high-resolution mass spectrometry coupled with liquid chromatography, it was possible to determine the molecular formula of thirty-nine flavonoids. Fragmentation analysis, ultraviolet spectrum and nuclear magnetic resonance data allowed the partial characterization of the structures of these compounds. The spectral dataset allowed the identification of a series of flavones in addition to the desoxyanthocyanidins common in extracts of the species. The occurrence of some of the proposed structures is uncommon in extracts of species of the Bignoniaceae family, and they are reported for the first time in the extract of this species. Quantitative analyses of total flavonoids confirmed the high content of these constituents in the species, with 4.09 ± 0.34 mg/g of dry plant material. The extract under study showed low in vitro cytotoxicity with CC50 ≥ 296.7 ± 1.4 µg/mL for Vero, LLC-MK2 and MRC-5 cell lines. In antiviral activity assays, inhibition of the cytopathic effects of Dengue, Zika and Mayaro viruses was observed, with EC50 values ranging between 30.1 and 40.9 µg/mL. The best result was observed against the Mayaro virus, with an EC50 of 30.1 µg/mL.

Real-Life Use of Ceftolozane/Tazobactam for the Treatment of Bloodstream Infection Due to Pseudomonas aeruginosa in Neutropenic Hematologic Patients: a Matched Control Study (ZENITH Study).

We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T.

Protein Intake, Adherence to Vitamin-Mineral Supplementation, and Dumping Syndrome in Patients Undergoing One Anastomosis Gastric Bypass.

INTRODUCTION: One anastomosis gastric bypass (OAGB) is an effective bariatric procedure. However, nutritional deficiencies or dumping syndrome (DS) may occur. The aim of this study was to assess adherence to nutritional recommendations and development of DS in a 3-year OAGB patient follow-up. METHODS: For 150 OAGB patients, in our center, data were collected through the electronic platform and by an individual telephone interview. The inclusion criterion is OAGB as a primary bariatric procedure, no revisional surgery, or no pregnancy. The adequacy of daily protein intake cutoff was defined as 60 g. Adherence to micronutrient supplementation protocol was considered if a minimum of 5 takes/week were reported. To evaluate the occurrence of DS, the Sigstad score questionnaire was used. For statistical analysis, a significance level less than 5% (p < 0.05) was considered. RESULTS: A total of 150 patients (80% females), BMI 44.3 ± 21.3 kg/m2, were subjected to the OAGB procedure. Of those, 128 fulfilled the study inclusion criteria. After 3 years, the mean %EBMIL was 78.4 ± 14.4. During the 3-year follow-up, the average protein intake was 60 g/day, and 48% reported an adequate daily protein intake. Adherence to the micronutrient supplementation protocol was reported by 70%. According to the Sigstad score questionnaire, DS was present in 24% of patients. CONCLUSION: A significant part of OAGB patients does not comply with the nutrition prescription assessed, emphasizing the need to improve team/patient communication strategies. Long-term studies are needed to characterize and assess the health impact of protein, vitamin, and mineral malnutrition in patients undergoing OAGB.

Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.

Aim: We evaluated the efficacy of a novel brain permeable "metformin-like" AMP-activated protein kinase activator, R481, in regulating glucose homeostasis. Materials and Methods: We used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively. Results: In vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo. Conclusions: These data demonstrate that peripheral administration of the brain permeable "metformin-like" AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.

Thrombin Inhibition: Preliminary Assessment of the Anticoagulant Potential of Turnera subulata (Passifloraceae).

Cardiovascular and thromboembolic disturbances are the main causes of disease-related deaths worldwide. Regardless of the etiological factors involved in thrombus formation, coagulation is mainly activated by thrombin, one of the most important blood clotting molecules. Thus, this study evaluated the Turnera subulata leaf crude extract, its ethyl acetate fraction effect on the coagulation cascade, and its possible side effects. Their phytocomposition indicated polyphenols, mainly flavonol-3-O-glycosylate and a flavone glycoside, without in vitro and in vivo toxicity. Regarding their potential anticoagulants, results displayed partial thromboplastin and prothrombin time activation, and Xa and IIa, and thrombin inhibition by heparin II cofactor, indicating significant anticoagulant activity, suggesting direct and indirect thrombin inhibition as the main mechanism of action. Therefore, T. subulata leaf active compounds exhibit therapeutic potential required to develop phytotherapeutic formulations to assist conventional anticoagulants in clinical treatments.

A Case-Control Study of Real-Life Experience with Ceftolozane-Tazobactam in Patients with Hematologic Malignancy and Pseudomonas aeruginosa Infection.

We present our experience in patients with hematologic malignancy and Pseudomonas aeruginosa infection treated with ceftolozane-tazobactam. We performed a single-center case-control study comparing patients with hematologic malignancy and P. aeruginosa infection treated with ceftolozane-tazobactam (study group) with similar patients not treated with ceftolozane-tazobactam (control group) to assess safety and efficacy. Nineteen cases and 38 controls were analyzed. Cases were younger (45.6 years versus 57.6 years; P = 0.012) and less frequently had bacteremia (52.6% versus 86.8%; P = 0.008). They also had worse Multinational Association for Supportive Care in Cancer (MASCC) scores (10.2 versus 16.1; P = 0.0001), more hospital-acquired infections (78.9% versus 47.4%; P = 0.013), and more extremely drug-resistant (XDR) P. aeruginosa infections (47.4% versus 21.1%; P = 0.015). Cases received a median of 14 days (7 to 18 days) of ceftolozane-tazobactam (monotherapy in 11 cases [57.9.6%]). Ceftolozane-tazobactam was mostly used as targeted therapy (16 cases; 84.2%) because of resistance (9 cases; 47.4%), failure (4 cases; 21.1%), and toxicity (3 cases; 15.8%). Ten cases had bacteremia (52.6%). The sources were pneumonia (26.3%), catheter-related bacteremia (21.1%), primary bacteremia (21.1%), and perianal/genital (15.7%), urinary (10.5%), and skin/soft tissue (5.3%) infection. No toxicity was attributed to ceftolozane-tazobactam. More than 60% had neutropenia, and 15.8% fulfilled the criteria for sepsis. There were no significant differences in clinical cure at day 14 (89.5% versus 71.1%; P = 0.183) or recurrence (15.8% versus 10.5%; P = 0.675). Thirty-day mortality was lower among cases (5.3% versus 28.9%; P = 0.045). Ceftolozane-tazobactam was well tolerated and at least as effective as other alternatives for P. aeruginosa infection in patients with hematologic malignancy, including neutropenic patients with sepsis caused by XDR strains.

Controlling Nerve Growth with an Electric Field Induced Indirectly in Transparent Conductive Substrate Materials.

Innovative neurostimulation therapies require improved electrode materials, such as poly(3,4-ethylenedioxythiophene) (PEDOT) polymers or IrOx mixed ionic-electronic conductors and better understanding of how their electrochemistry influences nerve growth. Amphibian neurons growing on transparent films of electronic (metal) conductors and electronic-ionic conductors (polymers and semiconducting oxides) are monitored. Materials are not connected directly to the power supply, but a dipole is created wirelessly within them by electrodes connected to the culture medium in which they are immersed. Without electrical stimulation neurons grow on gold, platinum, PEDOT-polystyrene sulfonate (PEDOT-PSS), IrOx , and mixed oxide (Ir-Ti)Ox , but growth is not related to surface texture or hydrophilicity. Stimulation induces a dipole in all conductive materials, but neurons grow differently on electronic conductors and mixed-valence mixed-ionic conductors. Stimulation slows, but steers neurite extension on gold but not on platinum. The rate and direction of neurite growth on PEDOT-PSS resemble that on glass, but on IrOx and (Ir-Ti)Ox neurites grow faster and in random directions. This suggests electrochemical changes induced in these materials control growth speed and direction selectively. Evidence that the electric dipole induced in conductive material controls nerve growth will impact electrotherapies exploiting wireless stimulation of implanted material arrays, even where transparency is required.

Vasorelaxant activity of Euphorbia furcillata Kunth mainly by activation of NO/cGMP pathway and calcium channel blockade / Actividad vasorrelajante de Euphorbia furcillata Kunth principalmente por activación de la vía NO/GMPc y bloqueo de canales de calcio]

The aim of current study was to determinate ex vivo and chromatographic fingerprint by HPLC of four extracts of Euphorbia furcillata K. Ethyl acetate extract of Euphorbia furcillata (EaEEf) was the most effective and potent extract (Emax=98.69±1.24%) and its effect was partially endothelium-dependent. Functional vasorelaxant mechanism of action of EaEEf was determinate, EaEEf showed efficient relaxation of KCl [80 mM]-induced contraction and norepinephrine and CaCl2 contraction curves showed diminution of maximal contraction in the presence of EAEEf and EaEEf-relaxation curve was shifted to the right in the presence of L-NAME (nitric oxide synthase inhibitor) and ODQ (guanylate cyclase inhibitor). Chromatographic fingerprints analysis suggests presence of diterpenoid such as abietane, tigliane, and ingenane skeletons. Our experiments suggest the EaEEf vasorelaxant activity could be attributed to diterpenoid molecules whose mechanism involves nitric oxide production and calcium channel blockade.

Se determinó el efecto vasorrelajante ex vivo y los perfiles cromatográficos mediante HPLC de cuatro extractos de Euphorbia furcillata K.. El extracto de acetato de etilo de E. furcillata (EaEEf) fue el más eficaz y potente en la contracción inducida por norepinefrina (Emax=98.69±1.24%) y el efecto fue parcialmente dependiente del endotelio vascular. Se determinó el mecanismo de acción vasorrelajante para EaEEf, este mostró ser eficaz sobre la contracción inducida por KCl [80 mM] y la curva de contracción en respuesta a norepinefrina y CaCl2 en presencia de EaEEf mostró disminución en la contracción máxima, mientras que la curva de relajación de EaEEf en presencia de L-NAME (inhibidor de óxido nítrico sintasa) y ODQ (inhibidor de guanilato ciclasa) se desplazó hacia la derecha. El análisis cromatográfico de EaEEf sugiere la presencia de moléculas diterpenoides como abietano, tigliano y esqueletos de ingenano. Nuestros resultados sugieren que el efecto vasorrelajante de EaEEf podría atribuirse a moléculas diterpenoides, cuyo mecanismo de acción involucra la producción de óxido nítrico y bloqueo de canales de calcio.

Immediate effects of Pilates based therapeutic exercise on postural control of young individuals with non-specific low back pain: A randomized controlled trial.

OBJECTIVES: Low back pain affects the person's ability to keep balance, especially in challenging conditions. The purpose of this study was to determine the immediate effects of Pilates exercises on postural sway and dynamic balance of young individuals with non-specific low back pain. DESIGN: Controlled laboratory design. SETTINGS AND MAIN OUTCOME MEASURES: Forty-six participants with non-specific low back pain were randomized to a Pilates (n=23, 10 males; age: 21.8±3.2years) and a control group (n=23, 9 males; age: 22.8±3.6years). Postural sway was assessed with a force platform and dynamic balance with the Star Excursion Balance Test, before and after the intervention or rest period. To assess postural sway, participants stood still on an unstable surface set on the force plate for 90s, with eyes closed. INTERVENTION: The intervention lasted 20min and consisted on four Pilates exercises: single leg stretch (level 1), pelvic press (level 1), swimming (level 1) and kneeling opposite arm and leg reach. RESULTS: At baseline, no differences were found between groups. The Pilates group improved in all the postural sway values (area of CoP: 11.5±3.4 to 9.7±2.7cm2, p=0.002 and CoP velocity: 2.8±0.6 to 2.3±0.5cm/s, p<0.001) and in the Star Excursion Balance Test. Control group only improved in CoP velocity, however, this improvement was significantly inferior compared to the Pilates group. CONCLUSIONS: Pilates exercises immediately improved postural sway and dynamic balance in young adults with non-specific low back pain.

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner.

AIM: To test the hypothesis that, given the role of AMP-activated protein kinase (AMPK) in regulating intracellular ATP levels, AMPK may alter ATP release from astrocytes, the main sources of extracellular ATP (eATP) within the brain. MATERIALS AND METHODS: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild-type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs). Cells were treated with drugs known to modulate AMPK activity: A-769662, AICAR and metformin, for up to 3 hours. Intracellular calcium was measured using Fluo4 and Fura-2 calcium-sensitive fluorescent dyes. RESULTS: In U373 cells, A-769662 (100 µM) increased AMPK phosphorylation, whereas AICAR and metformin (1 mM) induced a modest increase or had no effect, respectively. Only A-769662 increased eATP levels, and this was partially blocked by AMPK inhibitor Compound C. A-769662-induced increases in eATP were preserved in AMPK α1/α2 null MEF cells. A-769662 increased intracellular calcium in U373, HTAS and CRTAS cells and chelation of intracellular calcium using BAPTA-AM reduced A-769662-induced eATP levels. A-769662 also increased ATP release from a number of other central and peripheral endocrine cell types. CONCLUSIONS: AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 µM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway.

Evaluation of medicinal plants and colloidal silver efficiency against Vibrio parahaemolyticus infection in Litopenaeus vannamei cultured at low salinity.

In shrimp aquaculture, reduction in the use of synthetic antibiotics is a priority due to the high incidence of resistant bacteria (Vibrio) in the white shrimp Litopenaeus vannamei. An increasing number of studies show bactericidal activity of natural treatments in aquaculture. The effectiveness of neem (Azadirachta indica) and oregano (Lippia berlandieri) aqueous extracts and colloidal silver against V. parahaemolyticus were evaluated in low salinity shrimp culture. Results show that aqueous extracts of oregano and neem each present a minimum inhibitory concentration (MIC) of 62.50 mg ml-1 and inhibitory halos of 12.0 to 19.0 mm. Colloidal silver gave a MIC of 2 mg ml-1, and the inhibitory halos were found to be between 11.8 and 18.8 mm, depending on treatment concentrations. An in vivo challenge test was conducted on white shrimp postlarvae cultured at low salinity (5 practical salinity units, PSU), and a significant increase (p < 0.05) in survival was demonstrated in the presence of the aqueous extracts (oregano 64%, neem 76% and colloidal silver 90%), when compared to the control (0%) in the challenge test. However, no significant differences were observed between treatments, suggesting that they all act as alternative bactericidal source agents against V. parahaemolyticus infections for L. vannamei postlarvae when cultured at 5 PSU.

Avaliação da atividade antibacteriana dos extratos metanólico e hexânico do caule folhado de Melissa Officinalis / Evaluation of the Antibacterial Activity of Methanolic and Hexanic Extracts of Puff Pastry Stem, Melissa Officinalis / Evaluación de la actividad antibacterial de extractos metanol y hexano, el tallo rodadura Melissa Officinalis

Introdução: Melissa officinalis, da família Lamiaceae, é uma erva comumente utilizada na medicina popular. É conhecida no Brasil como Melissa, erva cidreira, cidrilha e melitéia. Tendo em vista que M.officinalis L é largamente utilizada na medicina popular, dentre elas para uso antibacteriano, este trabalho teve como principal objetivo avaliar a atividade antibacteriana e modulatória de extratos metanólico e hexânico do caule folhado de M. officinalis frente a cepas de bactérias padrões e multirresistentes. Materiais e métodos: Os extratosmetanólico e hexânico do caule folhado de M. officinalis L foram analisados para a atividade antibacteriana por meio de teste de microdiluição para determinação de concentração inibitória mínima (CIM) e modulação de aminoglicosídeos (gentamicina e amicacina). Resultados: Na avaliação DACIM foram obtidos resultados ≥1024 μg/mLcontra as bactérias (Escherichia coli e Staphylococcus aureus) em ambos extratos. O extrato metanólico mostrou resultados relevantes em associação com gentamicina potencializando o efeito contra E. coli e S. aureus quando associado à amicacina, nesta bactéria houve antagonismo. Já o extrato hexânico, resultou em uma redução da CIM de amicacina e gentamicina frente a linhagens de E. coli, mostrando efeito antagonista com a amicacina conta cepas de S. aureus. Conclusão: Conclui-se que o material vegetal influencia no comportamento dos antimicrobianos, tornando este trabalho importante como parâmetro para estudos mais aprofundados que possam combater a crescente resistência de bactérias patogênicas.

Introduction: Melissa officinalis, of the Lamiaceae family, is a herb commonly used on folk medicine. In Brazil it is known as Melissa, erva cidreira, cidrilha and meliteia. Considering that the M. Officinalis L is widely used in folk medicine, as for antibacterial use, among others, the main objective of this work was to evaluate the antibacterial and modulating activity of methanolic and hexanic extracts of M. officinalis L against pattern and multidrug resistant bacterial strains. Material and methods: The methanolic and hexanic extracts of the stem of puff pastry of M. officinalis L were analized to determine antibacterial activity by using the microdiluition for establishing the minimal inibitory concentration (MIC) and aminoglycosides (gentamicin and amikacin) modulation. Results: In the MIC evaluation, the results obtained were ≥1024 μg/mL against bacteria (Escherichia coli and Staphylococcus aureus) in both extracts. The methanolic extract showed important results when associated with gentamicin, since it potentiates its effect against E. coli and S. aureus when associated with amikacin, where antagonism was found. As to the hexanic extract, it showed a MIC reduction of amikacin and gentamicin against S. aureus strains. Conclusion: It was concluded that the plant material influences the antimicrobial behavior, a fact that makes this study an important parameter to deeper studies to combat the increase of pathogenic multidrug-resistant bacteria.

Introducción: Melissa Officinalis, de la familia Lamiaceae, es una hierba utilizada en la medicina popular. Es conocido en Brasil como erva cidreira, melisa, y melitéia cidrilha. Teniendo en cuenta que M. Officinalis L. se utiliza ampliamente en la medicina popular, entre ellos para uso antibacteriano, este trabajo tuvo como objetivo evaluar la actividad antibacteriana y modulador de extracto de metanol y hexano rodar el tallo de M. officinalis L. frente a las cepas de bacterias normas y las bacterias multirresistentes. Materiales y métodos: se analizó el extracto de metanol y hexano del tallo rodadura M. Officinalis L. para la actividad antibacteriana por una prueba de microdilución para la determinación de la Concentración Mínima Inhibitoria (MIC) y la modulación de aminoglucósidos (gentamicina y amikacina). Resultados: en la evaluación de la MIC los resultados obtenidos fueron ≥1024 μg/ml con contra las bacterias (Escherichia coli y Staphylococcus aureus) en ambos extractos. El extracto de metanol mostró resultados significativos en combinación con efecto potenciador gentamicina contra E. coli y s. Aureus cuando se combina con amikacina, esta bacteria era antagonismo. Ya extracto de hexano dio lugar a una reducción de la MIC de amikacina y gentamicina contra cepas de E. coli, que muestra el efecto antagónico con cepas de la cuenta de amikacina de S. Aureus. Conclusión: se concluye que el material vegetal influye en el comportamiento de los antimicrobianos, lo que hace este trabajo importante como parámetro para futuros estudios que puedan combatir la creciente resistencia de las bacterias.

Avaliação da atividade antibacteriana e moduladora dos extratos metanólico e hexânico da folha de Allium cepa / Evaluation of the Antibacterial and Modulating Activity of Methanolic and Hexanic Extracts of the Allium Cepa / Evaluación de la actividad antibacteriana y moduladora de los extractos metanol y hexano de la hoja de Allium cepa

Introdução: A resistência bacteriana tem crescido significativamente nos últimos tempos, tornando-se imprescindível a busca por novos alvos terapêuticos. Nesse contexto, compostos bioativos presentes em algumas plantas medicinais podem apresentar várias atividades biológicas, como ação antimicrobiana. Allium cepa conhecida popularmente como cebola é utilizada de maneira etnofarmacológica há muito tempo para o tratamento de diversas enfermidades: tuberculose, diabetes, hipertensão, reumatismo e assim por diante. Objetivo: O principal objetivo deste trabalho foi avaliar a atividade antimicrobiana e modulatória dos extratos metanólico e hexânicoda das folhas A. cepa frente às cepas de bactérias padrões e multirresistentes. Materiais e métodos: Pelos métodos e microdiluição e modulação com antibióticos. Resultados: Os resultados deste estudo demonstraram uma variação no CMI (Concentração Inibitória Mínima) de 128 a ≥ 1024 μg/mL dos extratos metanólico de A. cepa (EMAC) e hexânico de A. cepa (EHAC). Na modulação com os aminoglicosídeos (amicacina e gentamicina) observaram-se efeitos sinérgicos e antagônicos dos extratos EHAC e EMAC frente às cepas Escherichia coli e Staphylococcus aureus de linhagem multirresistente. Novas pesquisas são necessárias para uma possível utilização das plantas medicinais combinadas com os antimicrobianos frente às linhagens patogênicas. Conclusão: Através desses resultados sugere-se que os produtos naturais representam fontes promissoras no combate à resistência bacteriana.

Introduction: Bacterial resistance has grown significantly in recent years, making the search for new antibiotics imperative. Bioactive compounds in some medicinal plants may exhibit various biological activities as antimicrobial activity. Allium cepa, popularly known as onion, is ethnopharmacologically used for treating various diseases, such as tuberculosis, diabetes, hypertension and rheumatism; it is also considered a powerful bactericide. Objective: The main objective of this study was to evaluate the antimicrobial and modulating activity of methanol and hexane extracts of A. cepa against the strains of multiresistant bacteria. Materials and methods: Microdilution and modulation of antibiotics. Results: The results showed a variation in the MIC (Minimum Inhibitory Concentration) from 128 to ≥ 1024μg / mL between A. cepa methanol (EMAC) and A. cepa hexane (EHAC) extracts. Modulation with aminoglycosides (gentamicin and amikacin) have proved to have antagonistic effects of the extracts sinérgicose EHAC and EMAC against strains of multiresistant Escherichia coli and Staphylococcus aureus. Further research is needed related to the use of medicinal plants combined with antimicrobials against pathogenic strains. Conclusion: Through these results it can be inferred that natural products could constitute a promising source for combating bacterial resistance.

Introducción: la resistencia bacteriana ha crecido significativamente en los últimos años, por lo que es necesaria la búsqueda de nuevas dianas terapéuticas. En este contexto, los compuestos bioactivos presentes en algunas plantas medicinales pueden tener diversas actividades biológicas, tales como la acción antimicrobiana. Allium cepa, conocida como la cebolla, es utilizada, popularmente de forma etnofarmacológica para el tratamiento de diversas enfermedades tales como la tuberculosis, la diabetes, la hipertensión, el reumatismo y así sucesivamente. Objetivo: el objetivo de este estudio fue evaluar la actividad antimicrobiana y moduladora de extractos de metanol y hexano de Allium cepa frente a las cepas de bacterias y normas multirresistentes. Materiales y métodos: por los métodos microdilución y modulación con antibióticos. Resultados: los resultados mostraron una variación de MIC(concentración mínima inhibitoria) de 128 a ≥ 1024μg / mL dos extractos metanólicos A. cepa (EMAC) y hexano de A. cepa (EHAC). En la modulación con aminoglucósidos (amikacina y gentamicina), se observaron efectos sinérgicos y antagónicos de EHAC y EMAC, frente a las cepas de Escherichia coli y Staphylococcus aureus multirresistente. Se necesitan nuevas investigaciones para un posible uso de plantas medicinales combinadas con la cara antimicrobiana de las cepas patógenas. Conclusión: a partir de estos resultados, se sugiere que los productos naturales son fuentes prometedoras en la lucha contra la resistencia bacteriana.

New Trends on Antineoplastic Therapy Research: Bullfrog (Rana catesbeiana Shaw) Oil Nanostructured Systems.

Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable topical nanoemulsion and to evaluate its efficacy against melanoma cells. The oil samples were obtained by hot and organic solvent extraction processes and were characterized by titration techniques and gas chromatography mass spectrometry (GC-MS). The required hydrophile-lipophile balance and the pseudo-ternary phase diagram (PTPD) were assessed to determine the emulsification ability of the bullfrog oil. The anti-tumoral activity of the samples was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for normal fibroblast (3T3) and melanoma (B16F10) cell lines. Both extraction methods produced yielded around 60% and the oil was mainly composed of unsaturated compounds (around 60%). The bullfrog oil nanoemulsion obtained from PTPD presented a droplet size of about 390 nm and polydispersity = 0.05 and a zeta potential of about -25 mV. Both the bullfrog oil itself and its topical nanoemulsion did not show cytotoxicity in 3T3 linage. However, these systems showed growth inhibition in B16F10 cells. Finally, the bullfrog oil presented itself as a candidate for the development of pharmaceutical products free from cytotoxicity and effective for antineoplastic therapy.

Attitudes, Knowledge, Use, and Recommendation of Complementary and Alternative Medicine by Health Professionals in Western Mexico.

BACKGROUND: The use of complementary and alternative medicine (CAM) has increased in many countries, and this has altered the knowledge, attitudes, and treatment recommendations of health professionals in regard to CAM. METHODS: Considering Mexican health professionals׳ lack of knowledge of CAM, in this report we surveyed 100 biomedical researchers and Ph.D. students and 107 specialized physicians and residents of a medical specialty in Guadalajara, México (Western Mexico) with a questionnaire to address their attitudes, knowledge, use, and recommendation of CAM. RESULTS: We observed that significantly more researchers had ever used CAM than physicians (83% vs. 69.2%, P = .023) and that only 36.4% of physicians had ever recommended CAM. Female researchers tended to have ever used CAM more than male researchers, but CAM use did not differ between genders in the physician group or by age in either group. Homeopathy, herbal medicine, and massage therapy were the most commonly used CAMs in both the groups. Physicians more frequently recommended homeopathy, massage therapy, and yoga to their patients than other forms of CAM, and physicians had the highest perception of safety and had taken the most courses in homeopathy. All CAMs were perceived to have high efficacy (>60%) in both the groups. The attitude questionnaire reported favorable attitudes toward CAM in both the groups. CONCLUSIONS: We observed a high rate of Mexican health professionals that had ever used CAM, and they had mainly used homeopathy, massage therapy, and herbal medicine. However, the recommendation rate of CAM by Mexican physicians was significantly lower than that in other countries, which is probably due to the lack of CAM training in most Mexican medical schools.

Atividade antibacteriana e moduladora in vitro de extrato metanólico e hexânico de beta vulgaris spp. (Linnaeus) / Actividad antibacteriana y modulación in vitro de extractos de metanol y hexano del beta vulgaris spp. (Linnaeus) / Antibacterial activity and modulatory in vitro methanol and ethanol extracts of beta vulgaris spp. (Linnaeus)

Introdução: Beta vulgaris spp. conhecida popularmente como beterraba é bastante utilizada, além do consumo alimentar, de maneira etnofarmacológica para o combate de diversas infecções como: dores no trato gastrointestinal, inflamações crônicas, lesões nas genitais, inflamações nos ovários, cólicas, problemas renais, problemas cardíacos e diabetes. Objetivo: avaliar a atividade antibacteriana e modulatória dos extratos metanólicos e hexânicos dos frutos de B. vulgaris frente a cepas bacterianas padrões e multirresistentes, além de determinar as principais classes de metabólitos secundários. Métodos: os extratos metanólicos e hexânicos de B. vulgaris foram analisados para a atividade antibacteriana por meio de teste de microdiluição em caldo para determinação de Concentração Inibitória Mínima e modulação de aminoglicosídeos a gentamicina e amicacina. Resultados: às cepas de Staphylococcus aureus e Escherichia coli diminuiram a Concentração Inibitória Mínima de 64 µg/mL and 256 µg/mL quando combinadas aos antibióticos e extratos, Apresentando, portanto um efeito de aumento da atividade antibiótica, com exceção para o extrato hexânico em associação com a gentamicina contra cepas multirresistentes de Staphylococcus aureus. Conclusão: na prospecção fitoquímica foram evidenciados a presença de vários metabólitos secundários, o que pode explicar a ação bactericida desta planta. Portanto, diante dos resultados, B.vulgaris é uma fonte promissora no combate a resistência bacteriana(AU)

Introducción: Beta vulgaris SSP. conocido em lo popular como remolacha, es muy utilizado, además como consumo de alimentos, de manera etnofarmacológica para combatir varias infecciones como: dolores en el tracto gastrointestinal, inflamaciones crónicas, lesiones genitales, inflamaciones en ovarios, cólicos, problemas renales, diabetes y problemas del corazón. Objetivo: evaluar la actividad anti-bacteriana y moduladora de extractos metanólicos y hexânicos del fruto de B. vulgaris frente de cepas bacterianas multirresistentes estándares y además de determinar los principales metabolitos secundarios. Métodos: los extractos metanólicos y hexânicos de B. vulgaris fueron analizados para la actividad antibacteriana mediante prueba de microdilución en caldo para la determinación de la Concentración Mínima Inhibitoria y la modulación de aminoglicósidos gentamicina y amikacina. Resultados: las cepas de Staphylococcus aureus y Escherichia coli disminuyeron la Concentración Mínima Inhibitoria de 64 µ g/mL y 256 µ g/mL al combinarlos con antibióticos y los extractos, mostrando así un aumento de la actividad antibiótica. Excepto el extracto hexânico en combinación con la gentamicina contra cepas multirresistentes de Staphylococcus aureus. La fitoquímica evidencia la presencia de varios metabolitos secundarios que pueden explicar la acción bactericida de esta planta. Conclusión: los resultados de B. vulgaris muestran que es una fuente prometedora en la lucha contra la resistencia bacteriana(AU)

Introduction: Beta vulgaris spp. is popularly known as beets, widely used in ethno pharmacological way to fight various infections of the gastrointestinal tract such as pain, chronic inflammation, and sores on the genitals, inflammation of the ovaries, cramps, kidney problems, heart problems and diabetes. Objective: to evaluate the antibacterial and modulatory activity of methanol extracts of fruits and hexanic of B. vulgaris against strains of multiresistant bacterial and standards. In addition, to determining the major classes of secondary metabolites such as flavonoids and tannins. Methods: Hexane and methanol extracts of B. vulgaris were analyzed to antibacterial activity by the broth microdilution test for determination of Minimum Inhibitory Concentration and modulation and aminoglycosides such as amikacin, gentamicin. Results: the strains relevant of Escherichia coli and Staphylococcos aureus decreased Minimum Inhibitory Concentration of 64 mg/mL and 256 mg/mL thereof when combined antibiotic and extracts. Showing, so a enhancement effect of antibiotic activity, except for the hexane extract in combination with gentamicin against multidrug-resistant strains of Staphylococcus aureus. Conclusion: in phytochemical were shown the presence of various secondary metabolites, which may explain the bactericidal action of this plant. Therefore, given the results, B. vulgaris spp. is a promising source in combat bacterial resistance(AU)