Antitumoral photoinduced effects of crude extract, fractions, and naphthoquinones from Sinningia magnifica (Otto & A. Dietr.) Wiehler (Gesneriaceae) in a bioguided study.

Photodynamic therapy (PDT) has been used for various purposes, including as an antitumor resource in a noninvasive therapy with minimal side effects. Sinningia magnifica (Otto & A. Dietr.) Wiehler is a rupicolous plant found in rock crevices in Brazilian tropical forests. Initial studies indicate the presence of phenolic glycosides and anthraquinones in species of the genus Sinningia (Generiaceae family). It is known that anthraquinones are natural photosensitizers with potential PDT applications. This led us to investigate the potential compounds of S. magnifica for use as a natural photosensitizer against the melanoma (SK-MEL-103) and the prostate cancer (PC-3) cell lines in a bioguided study. Our results showed that singlet oxygen production by the 1,3-DPBF photodegradation assay greatly increased in the presence of crude extract and fractions. The biological activity evaluation showed photodynamic action against melanoma cell line SK-MEL-103 and prostate cell line PC-3. These results suggest the presence of potential photosensitizing substances, as demonstrated in this in vitro antitumor PDT study by the naphthoquinones Dunniol and 7-hydroxy-6-methoxy-α-dunnione for the first time. Naphthoquinones, anthraquinones and phenolic compounds were identified in the crude extract by UHPLC-MS/MS analysis, motivating us to continue with the bioguided phytochemical study aiming to discover more photochemically bioactive substances in Gesneriaceae plants.

Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society.

INTRODUCTION: Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. OBJECTIVE: To establish recommendations for CTD-ILD screening based on the current evidence. METHOD: Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. RESULTS: The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. CONCLUSIONS: Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.

Chimarrão, terere and mate-tea in legitimate technology modes of preparation and consume: A comparative study of chemical composition, antioxidant, anti-inflammatory and anti-anxiety properties of the mostly consumed beverages of Ilex paraguariensis St. Hil.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex paraguariensis St. Hil. (Aquifoliaceae) is a medicinal plant widely used by South American populations for centuries and is popularly attributed to stimulating and detoxifying properties. Nowadays, their consume traditionally occurs through three different beverages: chimarrão, terere and mate-tea. AIM OF THE STUDY: Although its composition and properties are well studied, literature lacks work comparing the potential of their extracts obtained by a legitimate preparation mode of their popular beverages. Therefore, the purpose of this research is to investigate changes in chemical composition, antioxidant activity, anti-inflammatory efficacy and anxiolytic effect from lyophilized aqueous extracts obtained simulating the legitimate popular preparation mode of chimarrão, terere and mate-tea. MATERIALS AND METHODS: In this work, were investigated differences related to preparation technology and dry material used through chemical composition analysis, with the lyophilized aqueous extracts obtained simulating the chimarrão, terere and mate-tea preparation. The chemical composition analysis comprises the total soluble phenolics content, chemical profiles by HPLC-ESI-MS/MS, and quantitative component detection by HPLC-UV/DAD. Moreover, evaluations of comparative antioxidant activity of the extracts (DPPH and ORACFL assays), anti-inflammatory efficacy and anxiolytic effect were performed in vivo. RESULTS: Our results showed that chimarrão extracts presented a richer composition in terms of phenolic compounds and purine alkaloids, and better antioxidant activity when compared to the other extracts. In pleurisy test, all products showed anti-inflammatory properties in the dose of 60 mg/kg. In the anxiolytic evaluation, although all extracts presented some effect, chimarrão and terere were better than mate-tea in general. No sign of toxicity was observed. CONCLUSIONS: Our findings support that the beverage made as chimarrão has the best composition and the most promising properties overall.

How much of skin improvement over time in systemic sclerosis is due to normal ageing? A prospective study with shear-wave elastography.

BACKGROUND: Measurement of skin involvement is essential for the diagnosis and assessment of prognosis and disease progression in systemic sclerosis (SSc). The modified Rodnan skin score (mRSS) is the gold standard measure of skin thickness, but it has been criticised for the lack of objectivity, poor inter-observer reproducibility and lack of sensitivity to change. Recently, shear-wave elastography (SWE) emerged as a promising tool for the objective and quantitative assessment of the skin in SSc patients. However, no studies have evaluated its sensitivity to change over time. OBJECTIVE: To assess changes in skin stiffness in SSc patients using SWE during a 5-year follow-up. METHODS: Skin stiffness [i.e. shear-wave velocity values (SWV) in metres per second] was assessed by SWE ultrasound (using virtual touch image quantification) at the 17 sites of the mRSS, in each participant, at baseline and follow-up. mRSS was performed at both time points. Differences between groups were analysed using the related-samples Wilcoxon signed-rank test and the Mann-Whitney U test. RESULTS: We included 21 patients [85.7% females; mean age 56.3 (10.4) years at baseline, 57.1% with limited SSc] and 15 healthy controls [73.3% females; mean age 53.6 (14.1) years)]. The median follow-up was 4.9 (0.4) years. Skin stiffness decreased significantly at all Rodnan sites (p ≤ 0.001) (except in the fingers), in SSc patients, over time. The same phenomenon occurred in controls, but to a lesser degree, in terms of percentage change. The percentage reduction in skin stiffness varied in the different Rodnan sites and in different phases of the disease. In addition, SWV values also decreased significantly in 15/16 skin sites with local normal Rodnan at baseline, whereas local Rodnan skin score only changed significantly in the upper arm (p = 0.046) and forearm (p = 0.026). CONCLUSION: This study provides first-time evidence suggesting that skin SWV values are more sensitive to change over time than mRSS and reduce significantly over time in SSc and normal controls.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

[Dermatomyositis-like syndrome in x-linked agammaglobulinemia]. / SÍNDROMA DERMATOMIOSITE-LIKE EM DOENTE COM AGAMAGLOBULINÉMIA LIGADA AO CROMOSSOMA X.

Primary immunodeficiencies (PIDs) encompass more than 250 different pathological conditions. X-linked agammaglobulinemia (XLA) has been occasionally associated with cutaneous and muscular manifestations resembling dermatomyositis, often termed dermatomyositis-like syndrome (DLS). This syndrome has been associated with cutaneous, muscular and central nervous system manifestations, accompanying a persistent infection by an Echovirus. According to sixteen previously reported cases, this syndrome has a poor prognosis. We report the case of a 27-years old male, with XLA and DLS, successfully treated with 6 cycles of human immunoglobulin and methotrexate. Clinical symptoms improved dramatically with a complete resolution of the musculoskeletal manifestations. Despite this clinical response, prognosis should remain reserved. The evolution of this syndrome remains unpredictable and therapeutic options are limited. To the best of our knowledge, there are only a few reports of similar cases which have survived so many months after the diagnosis.

Systematic screening of plant extracts from the Brazilian Pantanal with antimicrobial activity against bacteria with cariogenic relevance.

This study proposes a bioprospection methodology regarding the antimicrobial potential of plant extracts against bacteria with cariogenic relevance. Sixty extracts were obtained from ten plants--(1) Jatropha weddelliana, (2) Attalea phalerata, (3) Buchenavia tomentosa, (4) Croton doctoris, (5) Mouriri elliptica, (6) Mascagnia benthamiana, (7) Senna aculeata, (8) Unonopsis guatterioides, (9) Allagoptera leucocalyx and (10) Bactris glaucescens--using different extraction methods - (A) 70° ethanol 72 h/25°C, (B) water 5 min/100°C, (C) water 1 h/55°C, (D) water 72 h/25°C, (E) hexane 72 h/25°C and (F) 90° ethanol 72 h/25°C. The plants were screened for antibacterial activity at 50 mg/ml using the agar well diffusion test against Actinomyces naeslundii ATCC 19039, Lactobacillus acidophilus ATCC 4356, Streptococcus gordonii ATCC 10558, Streptococcus mutans ATCC 35688, Streptococcus sanguinis ATCC 10556, Streptococcus sobrinus ATCC 33478 and Streptococcus mitis ATCC 9811. The active extracts were tested to determine their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), cytotoxicity and chemical characterization. Forty-seven extracts (78%) were active against at least one microorganism. Extract 4A demonstrated the lowest MIC and MBC for all microorganisms except S. gordonii and the extract at MIC concentration was non-cytotoxic. The concentrated extracts were slightly cytotoxic. Electrospray ionization with tandem mass spectrometry analyses demonstrated that the extract constituents coincided with the mass of the terpenoids and phenolics. Overall, the best results were obtained for extraction methods A, B and C. The present work proved the antimicrobial activity of several plants. Particularly, extracts from C. doctoris were the most active against bacteria involved in dental caries disease.

Abarema cochliacarpos reduces LPS-induced inflammatory response in murine peritoneal macrophages regulating ROS-MAPK signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Abarema cochliacarpos (Gomes) Barneby and Grimes (Fabaceae), known by the vulgar name of Babatenã, has been traditionally used in Northeast Brazil, as an anti-inflammatory remedy. Previous studies have demonstrated its anti-inflammatory and antiulcer effects in skin lesion, alcohol gastric ulcer and acute and chronic colitis. AIMS: The present study was designed to evaluate the antioxidant and anti-inflammatory effects of the butanolic fraction from A. cochliacarpos (BFAC) and its major flavonoid, (+)-catechin, in LPS-stimulated murine peritoneal macrophages. Moreover, we studied the role of mitogen-activated protein kinase (MAPK)s and NF-kB signaling pathways possibly involved in the beneficial effects. MATERIALS AND METHODS: The quantification of the extract was carried out by ultra-performance liquid chromatography analysis. Cell viability was determined using SRB assay. Nitric oxide (NO) production was analyzed by Griess method and intracellular reactive oxygen species (ROS) by fluorescence analysis. In addition, cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) expression, MAPK activation and IkappaBalpha (IKBα) degradation, were determined by Western blot. RESULTS: After BFAC characterization, (+)-catechin was revealed as its major constituent. Both BFAC and (+)-catechin, exerted significant anti-oxidant and anti-inflammatory effects inhibiting LPS-induced intracellular ROS and NO production in peritoneal macrophages. Additionally, the extract but also its major component reduced pro-inflammatory proteins expression probably through c-Jun N-terminal kinase and p38 MAPK signaling pathways. CONCLUSION: These data suggest that the beneficial effects of BFAC might be mediated, at least in part, by the presence of (+)-catechin. Conclusively our findings confirm the potential of A. cochliacarpos as a new therapeutic strategy for the management of inflammatory and oxidative stress-related diseases.

[Septic arthritis and gout--a case report]. / Artrite séptica e gota--a propósito de um caso clínico.

The authors describe a 54 year-old male patient, admitted after presenting in the emergency room with acute oligoarthritis affecting the shoulders and right tibiotarsal and sternoclavicular joints, with a week's duration. He was non-febrile and related a purulent discharge from the stump of a traumatic amputation of the left thumb, starting a few days prior to the presenting complaints. There was a previous history of gouty arthritis and moderate alcoholism. Lab work revealed an elevation of the acute phase markers, with marked neutrophilia. Upon admittance, the patient underwent arthrocentesis, revealing a purulent discharge with sodium monourate crystals, which cultured positively for meticillin-sensitive Staphylococcus aureus. Besides antibiotherapy, on Day 5 the patient presented with a cervical abscess with extension to mediastinum; the abscess was drained by a cardiothoracic surgeon, and the right sternoclavicular and first costochondral articulations were found to be destroyed. The authors note that, although it is a rare occurrence septic arthritis can coexist with gout, while discussing the possible mecanisms of this association, as well as particular details of the clinical case presented.

[Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid syndrome: an unusual clinical association]. / Policondrite recidivante, dermatite intersticial granulomatosa e síndrome antifosfolípido: uma associação clínica invulgar.

The authors describe the case of a 49 year-old male patient with a 3-year history of antiphospholipid syndrome, admitted after presenting in the emergency room with erythematous nodular skin lesions, affecting the face and neck, with a week's duration. Local biopsies were suggestive of interstitial granulomatous dermatitis. The patient described lesions compatible with bilateral auricular chondritis, two weeks prior to the appearance of the nodules, which resolved spontaneously after 3 days. There was a previous episode of nasal chondritis, two years previously, and another episode starting at the 7th day of hospitalization. These findings, taken together with a diagnosis of seronegative polyarthritis established 5 years before the current events, lead to a diagnosis of relapsing polychondritis.

Anti-inflammatory activity of Blutaparon portulacoides ethanolic extract against the inflammatory reaction induced by Bothrops jararacussu venom and isolated myotoxins BthTX-I and II

This article reports the anti-inflammatory effect of Blutaparon portulacoides (B. portulacoides), specifically the ethanolic extract of its aerial parts, on the edema formation and leukocyte influx caused by Bothrops jararacussu (B. jararacussu) snake venom and Bothropstoxin-I and II (BthTX-I and II) isolated from this venom as an alternative treatment for Bothrops snakebites. The anti-inflammatory effect of B. portulacoides ethanolic extract was compared with an animal group pretreated with dexamethasone. B. portulacoides ethanolic extract significantly inhibited paw edema induced by B. jararacussu venom and by BthTX-I and II. Also, results demonstrated that the extract caused a reduction of the leukocyte influx induced by BthTX-I. However, the extract was not capable of inhibiting the leukocyte influx induced by the venom and by BthTX-II. In conclusion, these results suggest that the ethanolic extract of this plant possess components able to inhibit or inactivate toxins present in B. jararacussu venom, including its myotoxins, responsible for the edema formation. However, the leukocyte migration caused by the venom and BthTX-II was not inhibited by the plant, probably due to the different mechanisms involved in the edema formation and leukocyte influx. This is the first report of B. portulacoides extract as anti-inflammatory against snake venoms and isolated toxins.(AU)

[Hajdu-Cheney Syndrome: a case of acroosteolysis]. / Síndrome de Hajdu-Cheney: a proposito de um caso de acroosteolise.

Acroosteolysis is a rare clinical manifestation characterized by bone resorption of the terminal phalanges. It can occur in association with the variety of systemic diseases or be idiopathic. The authors describe a case of 47-year-old woman with acroosteolysis of distal phalanges since childhood, congenital amaurosis, premature loss of teeth and mal perforans. Because of the rate and exuberant manifestations found, with no etiological cause identified, the authors diagnosed Hajdu-Cheney Syndrome. Hajdu-Cheney is a rare, autosomal dominant disorder, with sporadic cases, apparently representing new mutations. Based on this case the authors review the differential diagnoses of acroosteolysis and the clinical manifestation of the Hajdu-Cheney syndrome

[Low back pain with 'red flags': a case of spondylodiscitis]. / Lombalgia com sinais de alarme: um ca50 de espondilodiscite.

Spondylodiscitis is a serious clinical entity. Despite the decrease in mortality from about 25% in the pre-antibiotic era to near 5%, it remains significant and the associated morbidity is still relevant. The rate of residual neurological deficits among survivors is around 7%. In 30% of patients some related symptoms persist, the most important being pain. The authors report the case of a 74-year-old male patient with recent onset low back pain, which caused considerable disability. With this work the authors intend to alert to the fact that in a patient with a common symptom such as low back pain, the presence of "red flags" requires a quick investigation and diagnosis in order to prevent serious damage.

Trypanocidal and antimicrobial activities of Moquinia kingii.

A chloroform crude extract (aerial part) and two compounds, apigenin (1) and cynaropicrin (2), isolated from Moquinia kingii were evaluated against Trypanosoma cruzi trypomastigotes in vitro. Antimicrobial activity was also screened using twenty-two strains including gram-positive and gram-negative bacteria and the yeasts Candida albicans and C. tropicalis. The chloroform crude extract, fractions and isolated compounds from M. kingii were active for both activities. The IC50 values for trypanocidal activity obtained for cynaropicrin and apigenin were 93.5 microg/ml and 181 microg/ml, respectively, while the minimum inhibitory concentrations (MICs) varied from 100 microg/ml to 2500 microg/ml, against the strains of bacteria and yeasts evaluated.

Antiprotozoal effect of crude extracts and flavonoids isolated from Chromolaena hirsuta (asteraceae).

Phytochemical study of Chromolaena hirsuta (Hook. & Arn.) R. King & H. Robinson crude extract (collected in Furnas, MG-Brasil) produced fifteen flavonoids, two triterpenes and five steroids. IR, UV,(1)H and (13)C NMR spectroscopy and GC analysis were used for the identification of these compounds. The dichloromethanic and ethanolic crude extracts (flowers and leaves) and six flavonoids isolated from this specie have been assayed for antiprotozoal activity against tripomastigote forms of Trypanosoma cruzi and promastigote forms of Leishmania amazonensis. The crude extracts significantly reduced the viability of T. cruzi and Leishmania amazonensis, and the six flavonoids showed considerable antiproliferative effect of development of two parasites evaluated. This is the fi rst report of antiprotozoal activity of extracts of C. hirsuta.

Bioactivity of crude extracts and some constituents of Blutaparon portulacoides (Amaranthaceae).

Crude extracts (aerial parts and roots, both dried), methylenedioxyflavonol, and a mixture of acyl steryl glycosides isolated from Blutaparon portulacoides, were assayed for their toxicity against Trypanosoma cruzi trypomastigotes and Leishmania amazonensis amastigotes from axenic cultures. The antimicrobial activity was also investigated, in a screening conducted using fifteen strains of Gram-positive and Gram-negative bacteria, along with the yeasts, Candida albicans and Candida tropicalis. To assess the antibacterial activity of the isolated compounds, the minimum inhibitory concentrations (MICs) were determined. There are no reports of acyl steryl glycosides in the genus Blutaparon and their biological activities are being evaluated for the first time.

Hypertension with orthostatic hypotension: interest of verapamil.

The purpose of this study was to investigate the effects of the calcium channel blocker verapamil in the management of patients with both high blood pressure and orthostatic hypotension. Six hypertensive patients, aged 37-78 years, mean 60.8 +/- 3.2 years, four men and two women, with symptomatic orthostatic hypotension were included in this open study. Verapamil, 240 to 360 mg/day, decreased blood pressure and did not impair orthostatic hypotension with a mean follow-up of 6 months. Blood pressure and heart rate were, in lying and standing position, respectively, as follows: 177.5 +/- 5.9/99.1 +/- 9.9 mm Hg and 81.0 +/- 9.0 beats/min and 120.0 +/- 4.8/83.3 +/- 4.0 mm Hg and 91.0 +/- 9.5 beats/min before treatment; then, 155.8 +/- 5.5/89.1 +/- 4.2 mm Hg and 74.5 +/- 8.6 beats/min and 127.5 +/- 7.3/83.3 +/- 4 mm Hg and 83.0 +/- 9.1 beats/min after verapamil. In three patients with orthostatic hypotension successfully treated by the peripheral dopaminergic antagonist domperidone 60 mg/day, the subsequent introduction of verapamil 240 mg/day did not modify the standing-induced decrease in systolic blood pressure: 46.6 mm Hg under domperidone and 30.0 mm Hg under domperidone plus verapamil. Verapamil increased baroreflex sensitivity from 1.4 to 3.5 ms/mm in all patients. This preliminary study shows the interest of verapamil in the difficult management of hypertension with orthostatic hypotension. It is suggested that verapamil could increase the baroreflex sensitivity in patients with orthostatic hypotension.