Vanilla from Brazilian Atlantic Forest: In vitro and in silico toxicity assessment and high-resolution metabolomic analysis of Vanilla spp. ethanolic extracts.

The natural vanilla market, which generates millions annually, is predominantly dependent on Vanilla planifolia, a species characterized by low genetic variability and susceptibility to pathogens. There is an increasing demand for natural vanilla, prized for its complex, authentic, and superior quality compared to artificial counterparts. Therefore, there is a necessity for innovative production alternatives to ensure a consistent and stable supply of vanilla flavors. In this context, vanilla crop wild relatives (WRs) emerge as promising natural sources of the spice. However, these novel species must undergo toxicity assessments to evaluate potential risks and ensure safety for consumption. This study aimed to assess the non-mutagenic and non-carcinogenic properties of ethanolic extracts from V. bahiana, V. chamissonis, V. cribbiana, and V. planifolia through integrated metabolomic profiling, in vitro toxicity assays, and in silico analyses. The integrated approach of metabolomics, in vitro assays, and in silico analyses has highlighted the need for further safety assessments of Vanilla cribbiana ethanolic extract. While the extracts of V. bahiana, V. chamissonis, and V. planifolia generally demonstrated non-mutagenic properties in the Ames assay, V. cribbiana exhibited mutagenicity at high concentrations (5000 µg/plate) in the TA98 strain without metabolic activation. This finding, coupled with the dose-dependent cytotoxicity observed in WST-1 (Water Soluble Tetrazolium) assays, a colorimetric method that assesses the viability of cells exposed to a test substance, underscores the importance of concentration in the safety evaluation of these extracts. Kaempferol and pyrogallol, identified with higher intensity in V. cribbiana, are potential candidates for in vitro mutagenicity. Although the results are not conclusive, they suggest the safety of these extracts at low concentrations. This study emphasizes the value of an integrated approach in providing a nuanced understanding of the safety profiles of natural products, advocating for cautious use and further research into V. cribbiana mutagenicity.

Marketable 1,3-dimethylamylamine and caffeine-based thermogenic supplements: Regulatory genotoxicity assessment through in vitro and in silico approaches.

The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing Salmonella/microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and in silico for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. In silico predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.

Toxicogenetic assessment of a pre-workout supplement: In vitro mutagenicity, cytotoxicity, genotoxicity and glutathione determination in liver cell lines and in silico ADMET approaches.

The benefits of practicing physical activity, such as weight loss and control, are commonly associated with caloric restriction diets and may be improved by the ingestion of thermogenic and ergogenic supplements. However, there is a lack of safety data on commonly marketed nutritional supplements. Therefore, this investigation aims to evaluate a pre-workout supplement for mutagenicity using the Ames test, hepatocytoxicity in HepG2 and F C3H cells after 24 h, 48 h and 72 h, genotoxicity using the CBMN assay, determination of gluthatione activity and computational prediction of the three major isolated compounds present in the supplement. The mutagenicity test showed a mutagenic response in TA98 His+ revertants of 5 mg/plate in the presence of metabolic activation, cytotoxicity in TA98 of 5 mg/plate in the absence of metabolic conditions, and in TA102 of 0.5 mg/plate both in the presence and absence of metabolic activation. In our in vitro eukaryotic cell viability, WST-1, LDH and alkaline phosphatase assays, the supplement showed hepatocytotoxicity both dose-dependently and time-dependently. In the cytokinesis blocking micronuclei assay, the supplement induced micronuclei, nuclear buds, nucleoplasmatic, bridge formation, and a decreased in nuclear division. In addition, the supplement decreased intra and extracellular GSH. Computational analysis showed that the three isolated compounds most present in the supplement have the potential to cause hepatotoxicity. In the present investigation, the pre-workout supplement induced mutagenic, genotoxic, and cytotoxic responses and GSH decrease. Thus, considering food safety and public health sanitary vigilance, the consumption of this pre-workout supplement may harm the health of its consumers.

Colonic Kaposi's sarcoma as the first clinical manifestation of undiagnosed HIV.

A 52-year-old male, without significant past medical history, is referred for new onset constipation, hematochezia and significant weight loss. Blood tests were unremarkable. A colonoscopy was performed, showing reddish, hematocystic and friable mucosa in a circumferential pattern in the rectum, with similar patches throughout the whole colon, one of them infiltrating the ileocecal valve. Biopsies were obtained and revealed spindle cell proliferation immunoreactive for CD34 and herpesvirus 8 (HHV-8), compatible with Kaposi's sarcoma (KS). HIV serologies were subsequently done, with a positive result, the patient then reporting previous heterosexual unprotected sexual activities. He was started on highly active antiretroviral therapy (HAART) and chemotherapy with liposomal doxorubicin, with a favorable outcome to this date. KS is a low-grade tumor of the vascular endothelium that requires infection with HHV-8. HIV-related KS is more commonly diagnosed in homosexual males with uncontrolled HIV infection and is associated with a variable clinical course. The gastrointestinal tract is involved in up to 51% of patients, but since the majority is clinically silent (70%), visceral involvement is probably underestimated. The treatment goal is symptomatic relief, and may range from HAART alone to a combination with systemic chemotherapy, depending on disease extent. We present this case given its endoscopic exuberance, with biopsies showing an HIV-defining condition, in a patient unaware of his diagnosis.

Hepatocellular Carcinoma with Atrial Extension: A Case Report.

Hepatocellular carcinoma is a common malignancy usually associated with cirrhosis. Despite being a highly aggressive tumor with several cases of vascular invasion, metastatic disease to the heart is a rare condition. A 65-year-old male cirrhotic patient was admitted with dyspnea, ascites, and lower extremity edema. A transthoracic echocardiogram showed a large mass in the right atrium. Further imaging studies revealed the presence of hepatocellular carcinoma extending from the liver to the right atrium through the inferior vena cava. The cardiac mass was surgically removed to treat the symptoms of right heart failure, but unfortunately the patient died on the 30th day after surgery due to septic shock.

O carcinoma hepatocelular é uma neoplasia comum, maioritariamente associada à cirrose hepática. Apesar de se tratar de uma entidade clínica agressiva com predisposição à invasão vascular, a doença metastática com envolvimento cardíaco é rara. Os autores reportam o caso de um homem de 65 anos com cirrose hepática que recorreu ao serviço de urgência por um quadro clínico de dispneia, ascite e edema periférico. Foi realização ecocardiograma transtorácico à admissão, que revelou presença de uma massa a nivel da aurícula direita. A investigação clínica, laboratorial e imagiológica realizada permitiu o diagnóstico de carcinoma hepatocelular com extensão desde o fígado até à aurícula direita através da veia cava inferior. A massa intracardíaca foi removida cirurgicamente para alivio sintomático, no entanto o doente faleceu no 30° dia de pós-operatório devido a choque séptico.

In vitro biochemical characterization and genotoxicity assessment of Sapindus saponaria seed extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Sapindus saponaria, also popularly known as soapberry, has been used in folk medicinal values because of its therapeutic properties and several compounds in its composition, which represent a target in potential for drug discovery. However, few data about its potential toxicity has been reported. AIM OF THE STUDY: Plant proteins can perform essential roles in survival, acting as defense mechanism, as well functioning as important molecular reserves for its natural metabolism. The aim of the current study was to investigate the in vitro toxicity profile of protein extract of S. saponaria and detect protein potentially involved in biological effects such as collagen hydrolysis and inhibition of viral proteases. MATERIALS AND METHODS: Protein extract of soapberry seeds was investigated for its cytotoxic and genotoxic action using the Ames test. The protein extract was also subjected to a partial purification process of a protease and a protease inhibitor by gel chromatography filtration techniques and the partially isolated proteins were characterized biochemically. RESULTS: Seed proteins extract of S. saponaria was evaluated until 100 µg/mL concentration, presenting cytotoxicity and mutagenicity in bacterial model mostly when exposed to exogenous metabolic system and causing cytotoxic and genotoxic effects in HepG2 cells. The purification and partial characterization of a serine protease (43 kDa) and a cysteine protease inhibitor (32.8 kDa) from protein extract of S. Saponaria, corroborate the idea of ​​the biological use of the plant as an insecticide and larvicide. Although it shows cytotoxic, mutagenic and genotoxic effects. CONCLUSION: The overall results of the present study provide supportive data on the potential use of proteins produced in S. saponaria seeds as pharmacological and biotechnological agents that can be further explored for the development of new drugs.

Lower Gastrointestinal Bleeding Associated With Sodium Polystyrene Sulfonate Use.

Sodium polystyrene sulfonate (kayexalate) is a cation-exchange resin widely used in the management of hyperkalemia. Gastrointestinal adverse events are uncommon; symptoms are nonspecific, and mucosal injury can range from mild ulceration to bowel perforation. An 81-year-old man was admitted because of decompensation of cirrhosis with acute kidney injury and hyperkalemia, treated with sodium polystyrene sulfonate. During admission, he presented multiple episodes of hematochezia, accompanied by tachycardia and hemoglobin drop. Colonoscopy revealed colonic ulceration, and histopathological findings were compatible with ulceration due to kayexalate injury. Despite rare, the widespread use of sodium polystyrene sulfonate puts a large population at risk of serious complications related to its use.

Plinia cauliflora (Mart.) Kausel (Jaboticaba) leaf extract: In vitro anti-Trypanosoma cruzi activity, toxicity assessment and phenolic-targeted UPLC-MSE metabolomic analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel, known as Brazilian grape or jaboticaba, is widely used in Brazilian traditional medicine to treat infectious and inflammatory disorders. However, several aspects of its biological potential remain unclear, such as toxicity and effects on pathogenic protozoa. AIM OF THE STUDY: Investigate the phenolic composition, the in vitro and in silico toxicity profile, and the anti-Trypanosoma cruzi activity of the phenolics-enriched hydromethanolic extract of P. cauliflora leaf. MATERIAL AND METHODS: Phytochemical analysis was performed ultra-performance liquid chromatography-mass spectrometry (UPLC-MSE). Mutagenicity, genotoxicity and eukaryotic cytotoxicity was evaluated by Ames test, cytokinesis-block micronucleus and colorimetric assays, respectively, alongside with a computational prediction of the major compound's pharmacokinetics and toxicity. Anti-T. cruzi activity was investigated on T. cruzi bloodstream trypomastigotes. RESULTS: A total of 14 phenolic compounds were identified, including 11 flavonoids and 2 phenolic acids. No positive response regarding mutagenic potential was detected in Salmonella strains TA97, TA98, TA100, TA102, TA104, both in absence or presence of metabolic activation. The extract induced significant dose-response reduction on nuclear division indexes of HepG2 cells, suggesting cytostatic effects, with no micronuclei induction on cytokinesis-block micronucleus assay. Likewise, it also presented cytotoxic effects, inducing HepG2 and F C3H dose and time dependently cell death through cell membrane damage and more evidently by mitochondrial dysfunction. A dose-response curve of in vitro trypanocidal activity was observed against T. cruzi bloodstream trypomastigotes after 2 and 24 h of exposure. In silico predictions of most abundant compounds' structural alerts, pharmacokinetics and toxicity profile indicates a moderately feasible druglikeness profile and low toxicity for them, which is compatible with in vitro results. CONCLUSIONS: The present study demonstrated that P. cauliflora leaf extract is a potential source of antiparasitic bioactive compounds, however it presents cytotoxic effects in liver cell lines.

Reduced heart-rate variability and increased risk of hypertension-a prospective study of the ELSA-Brasil.

Although autonomic disturbances are known to precede hypertension onset, the risks underlying different ranges of blood pressure and impaired cardiac autonomic modulation are still unknown. This study aimed to identify the risk of hypertension incidence related to low heart-rate variability profile in normotensive blood pressure subcategories: normal (<120/80 mmHg) and prehypertension (120/80-139/89 mmHg) in a 4-year follow-up. 7665 participants free of hypertension at baseline were examined. They were allocated into one of two groups (

Primary hepatic lymphoma in a patient with cirrhosis: a case report.

BACKGROUND: Primary hepatic lymphoma is a very uncommon disease. Due to its nonspecific clinical, laboratory, and imaging findings, it is often misdiagnosed. Liver biopsy is required to make a final diagnosis. Chemotherapy is the current gold standard of treatment. CASE PRESENTATION: An asymptomatic 65-year-old Caucasian man with Child-Pugh class A cirrhosis presented to our hospital with a nodular lesion seen on a routine surveillance abdominal ultrasound. His physical examination revealed hepatomegaly and no other significant findings. Magnetic resonance imaging of the abdomen showed a voluminous nodule on the left lobe with heterogeneous contrast enhancement. His liver biopsy was compatible with diffuse large B-cell lymphoma. Systemic staging showed no evidence of nodal or bone marrow involvement, confirming the diagnosis of primary hepatic lymphoma. He was treated with chemotherapy. However, he developed febrile neutropenia after one of the cycles and died. CONCLUSIONS: In this article, we report a rare presentation of non-Hodgkin lymphoma and review the current literature on clinical features, diagnosis, and management.

Diabetes and subclinical hypothyroidism on heart rate variability.

BACKGROUND: We aimed to analyse if the effects of coexistent diabetes and subclinical hypothyroidism extend to the cardio autonomic nervous system, using heart rate variability baseline data from the Brazilian Longitudinal Study of Adult Health. MATERIALS AND METHODS: Heart rate variability analyses were performed by linear time and frequency domains in 5-minute time series collected in the supine position. The associations of diabetes and subclinical hypothyroidism with the lowest quartile group for heart rate and the highest quartile group for each heart rate variability parameter were analysed using additive and multiplicative terms in logistic models. For the first approach, the subsample was categorized into four groups: subjects without diabetes and normal thyroid function (controls); subjects without diabetes and subclinical hypothyroidism; patients with diabetes and normal thyroid function; and patients with diabetes and subclinical hypothyroidism. For the interaction alnalysis, diabetes and subclinical hypothyroidism diagnoses were included in separate, along with a multiplicative interaction term between them. RESULTS: Point odds ratio estimates for the 4th quartiles of heart rate, and 1st quartiles of all heart rate variability measurements were higher for subjects with combined diabetes and subclinical hypothyroidism than for diabetes only, independently of main sociodemographic and clinical variables (HR: 8.33 vs 2.63; SDNN: 2.59 vs 1.61; RMSSD: 2.37 vs 1.42; LF: 2.83 vs 1.71; HF: 3.06 vs 1.39), but not independently of HbA1c and TSH. Only the interaction term for the association with heart rate, adjusted for sociodemographic and clinical variables, had borderline statistical significance. CONCLUSION: Diabetes and subclinical hypothyroidism exert a potential joint impact on cardiac autonomic control, showed by additive effects between diabetes and subclinical hypothyroidism, as well as a significant interaction term for the association with heart rate.

Prevalence, risk factors and global impact of musculoskeletal injuries among endoscopists: a nationwide European study.

Background and study aims Previous studies have suggested a high prevalence of musculoskeletal injuries (MI) in endoscopists. Little evidence has come from European countries. Our main aim was to evaluate the prevalence, type, and impact of MI among Portuguese endoscopists. We also sought to identify risk factors for the development, severity and number of endoscopy-related MI. Material and methods A 48-question electronic survey was developed by a multidisciplinary group. The electronic survey was sent to all members of Portuguese Society of Gastroenterology (n = 705) during May 2019. Study data were collected and managed using REDCap electronic data capture tools hosted at SPG - CEREGA. Results The survey was completed by 171 endoscopists (response rate of 24.3 %), 55.0 % female with a median age of 36 years (range 26-78). The prevalence of at least one MI related to endoscopy was 69.6 % (n = 119), the most frequent being neck pain (30.4 %) and thumb pain (29.2 %). The median time for MI development was 6 years (range 2 months-30 years). Severe pain was reported by 19.3 %. Change in endoscopic technique was undertaken by 61.3 % and reduction in endoscopic caseload was undertaken by 22.7 %. Missing work was reported by 10.1 %, with the median time off from work being 30 days (range 1-90). Female gender and ≥ 15 years in practice were independently associated with MI and severe pain. Years in practice, weekly-time performing endoscopy, and gender were significant predictors of the number of MI. Conclusions Prevalence of MI was significant among Portuguese endoscopists and had a relevant impact on regular and professional activities.

Experiência com a Transmissão de um programa sobre automedicação por meio de uma Web Rádio / Experience with the transmission of a program about self-medication through a Web Radio

Objetivo: descrever a experiência com alunos de uma escola estadual, após transmissão de um programa sobre automedicação por meio de uma web rádio com participação ativa da juventude. Metodologia: estudo descritivo do tipo relato de experiência, do projeto de extensão Web Cuidado em Infância e Juventude nas Escolas da Universidade Federal do Piauí, desenvolvido na cidade de Picos com alunos do nono ano de uma escola pública. Obteve aprovação do Comitê de Ética em Pesquisa da Universidade Estadual do Ceará com o parecer 11043817-5. Resultados: com o desenvolvimento da atividade foi verificado um grande aproveitamento com influência de melhorias educacionais sobre automedicação, um tema relevante para a saúde humana, envolvendo a tecnologia da Web Rádio. Teve a participação ativa dos alunos com aprendizado sobre o tema e as dúvidas mais frequentes foram relativas às consequências (50%). Conclusão: o encontro na escola mostrou-se um dia construtivo de aprendizagem, onde os alunos participantes tiveram a oportunidade de tirarem suas dúvidas sobre o tema em discussão e a transmissão de informações por recursos tecnológicos mostrou-se uma necessidade de atividades de promoção sobre a temática.

Objective: to describe the experience with students of a state school, after broadcasting a program on selfmedication through a web radio with active participation of youth. Methodology: it is a descriptive study of the experience report type, from the Web Care in Childhood and Youth extension project at the Schools of the Federal University of Piauí, developed in the city of Picos with students from the ninth year of a public school. It was approved by the Research Ethics Committee of the State University of Ceará with the report 11043817-5. Results: with the development of the activity was verified that there was a great use with the influence of educational improvements on self-medication, a relevant topic for human health, involving the technology of Web Radio. There was the active participation of students with learning on the topic and the most frequent doubts were related to the consequences (50%). Conclusion: the meeting at the school proved to be a constructive learning day, where the participating students had the opportunity to clarify their doubts about the topic under discussion and the transmission of information by technological resources proved to be a need for promotional activities on the subject thematic.