The Cardiometabolic Impact of Rebaudioside A Exposure during the Reproductive Stage.

The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.

Large Immature Intracranial Teratoma in an Infant: A Case Report.

Intracranial immature teratomas are rare, highly malignant, and fast-growing with a poor prognosis. We report the case of an infant with a large immature teratoma in the intracranial compartment. A two-month-old child presented to the emergency room with drowsiness and seizures. CT and cranial MRI showed hydrocephalus with a large expansive process in the right cerebral hemisphere extending to the infratentorial compartment, compressing the cerebellum and brainstem. It was then decided to partially resect the lesion. Postoperatively, due to the aggressiveness of the residual tumor, the patient developed complications (status epilepticus, hyperthermia, and electrolyte disorders) and died. Histopathological and immunohistochemical studies confirmed an immature teratoma. Teratomas are a subtype of germ cell tumors. Immature teratomas contain a population of cells that retain embryonic characteristics and tissues with more primitive components derived from all or some of the three germ layers (ectoderm, mesoderm, and endoderm). The prognosis of immature teratomas is associated with the degree of tumor differentiation, and those composed of undifferentiated embryonic tissues have a poor prognosis. This case report illustrates the rare and severe occurrence of a bulky immature cerebral teratoma in an infant. Unfortunately, despite undergoing a planned partial resection, the infant ended up having complications and died. Therefore, due to the size of the lesion in an infant, these cases are always complex when deciding on a surgical approach.

Determination of phytocannabinoids in cannabis samples by ultrasound-assisted solid-liquid extraction and high-performance liquid chromatography with diode array detector analysis.

The characterisation of cannabis plants, especially the determination of specific phytocannabinoids, has gained enormous importance in the last decade, mainly due to the recent changes in cannabis control in several countries or states. This is particularly relevant for the forensic, medical or recreative industry to have a rapid, inexpensive, and reliable methodology to identify and quantify phytocannabinoids. Furthermore, spiking cannabis products with Δ8-tetrahydrocannabinol (THC) is a contemporary trend that demands improving or replacing current methods to include this cannabinoid. The current study presents an ultrasound-assisted solid-liquid extraction followed by high-performance liquid chromatography with diode array detection (HPLC-DAD) methodology to identify and quantify Δ9-THC, Δ8-THC, cannabidiol, cannabinol, Δ9-tetrahydrocannabinolic acid and cannabidiolic acid in cannabis products. The herbal samples were extracted with ethanol:acetonitrile (50:50, v:v) by ultrasonication using only 50 mg of sample. The plant oils were diluted in ethanol. The optimised procedure allowed ≈100% extraction efficiency of the target cannabinoids. The validation assays showed that the method is linear (R2 > 0.997), selective, sensitive, precise and accurate, with suitable limits of detection (0.125-0.250 µg mL-1) and quantification (0.500 µg mL-1). The method was successfully applied to cannabis samples, demonstrating its suitability for routine analyses. This contribution follows the current demand for fast and straightforward analysis services of this plant and its derivatives, using small amounts of sample. The present study compares very favourably against other works, particularly in regards to the extraction efficiency, speed of the overall procedure, method sensitivity, and ability to monitor Δ8-THC spiked samples using a novel solvent mixture.

Novel Psychoactive Substances: The Razor's Edge between Therapeutical Potential and Psychoactive Recreational Misuse.

BACKGROUND: Novel psychoactive substances (NPS) are compounds of natural and synthetic origin, similar to traditional drugs of abuse. NPS are involved in a contemporary trend whose origin lies in a thinner balance between legitimate therapeutic drug research and legislative control. The contemporary NPS trend resulted from the replacement of MDMA by synthetic cathinones in 'ecstasy' during the 2000s. The most common NPS are synthetic cannabinoids and synthetic cathinones. Interestingly, during the last 50 years, these two classes of NPS have been the object of scientific research for a set of health conditions. METHODS: Searches were conducted in the online database PubMed using boolean equations. RESULTS: Synthetic cannabinoids displayed protective and therapeutic effects for inflammatory, neurodegenerative and oncologic pathologies, activating the immune system and reducing inflammation. Synthetic cathinones act similarly to amphetamine-type stimulants and can be used for depression and chronic fatigue. CONCLUSIONS: Despite the scientific advances in this field of research, pharmacological application of NPS is being jeopardized by fatalities associated with their recreational use. This review addresses the scientific achievements of these two classes of NPS and the toxicological data, ending with a reflection on Illicit and NPS control frames.

Toxicological effects of the rare earth element neodymium in Mytilus galloprovincialis.

The wide range of applications of rare earth elements (REE) is leading to their occurrence in worldwide aquatic environments. Among the most popular REE is Neodymium (Nd), being widely used in permanent magnets, lasers, and glass additives. Neodymium-iron-boron (NdFeB) magnets is the main application of Nd since they are used in electric motors, hard disk drives, speakers and generators for wind turbines. Recent studies have already evaluated the toxic potential of different REE, but no information is available on the effects of Nd towards marine bivalves. Thus, the present study evaluated the biochemical alterations caused by Nd in the mussel Mytilus galloprovincialis exposed to this element for 28 days. The results obtained clearly demonstrated that Nd was accumulated by mussels, leading to mussel's metabolic capacity increase and GLY expenditure, in an attempt to fuel up defense mechanisms. Antioxidant and biotransformation defenses were insufficient in the elimination of ROS excess, resulting from the presence of Nd and increased electron transport system activity, which caused cellular damages (measured by lipid peroxidation) and loss of redox balance (assessed by the ratio between reduced and oxidized glutathione). The results obtained clearly highlight the potential toxicity of REEs and, in particular of Nd, with impacts at cellular level, which may have consequences in mussel's survival, growth and reproduction, affecting mussel's population.

Macrophage activation and leishmanicidal activity by galactomannan and its oxovanadium (IV/V) complex in vitro.

Compounds that activate macrophage antimicrobial activity are potential targets for treatment of leishmaniasis. The present study investigated the in vitro immunomodulatory effects of a galactomannan (GALMAN-A) isolated from seeds of Mimosa scabrella and its oxovanadium (IV/V) complex (GALMAN-A:VO(2+)/VO(3+)) on macrophage activity. GALMAN-A increased nitric oxide levels by ~33% at a concentration of 250µg/ml, while GALMAN-A:VO(2+)/VO(3+) decreased nitric oxide levels by ~33% at a concentration of 50µg/ml. Furthermore, GALMAN-A increased interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) levels by 5.5 and 2.3 times, respectively, at a concentration of 25µg/ml; at the same concentration, GALMAN-A:VO(2+)/VO(3+) promoted an increase in IL-1ß and IL-6 production by 8 and 5.5 times, respectively. However, neither GALMAN-A nor GALMAN-A:VO(2+)/VO(3+) affected tumor necrosis factor alpha (TNF-α) or interleukin-10 (IL-10) levels. Importantly, both GALMAN-A and GALMAN-A:VO(2+)/VO(3+) exhibited leishmanicidal activity on amastigotes of Leishmania (L.) amazonensis, reaching ~60% activity at concentrations of 100 and 25µg/ml, respectively. These results indicate that GALMAN-A is three times more potent and its oxovanadium complex is twelve times more potent than Glucantime (300µg/ml), which is the drug of choice in leishmaniasis treatment. The IC50 value for GALMAN-A:VO(2+)/VO(3+) was 74.4µg/ml (0.58µg/ml of vanadium). Thus, the significant activation of macrophages and the noted leishmanicidal effect demonstrate the need for further studies to clarify the mechanisms of action of these compounds.

Acetylcholinesterase inhibitory activity of uleine from Himatanthus lancifolius.

Application of acetylcholinesterase (AChE) inhibitors is the primary treatment for Alzheimer's disease. Alkaloids, such as physostigmine, galanthamine, and huperzine A, play an important role as AChE inhibitors. The aim of this work was to evaluate Himatanthus lancifolius (Muell. Arg.) Woodson, a Brazilian species of Apocynaceae, and its main indole alkaloid uleine, in order to identify new AChE inhibitors. The plant fluid extract, fractions, and uleine were tested for AChE inhibitory activity using Ellman's colorimetric method for thin-layer chromatography (TLC), 96-well microplates, and also Marston's TLC colorimetric method. Both TLC assays showed similar results. At 5 mg/mL, the fluid extract inhibited the AChE enzyme by (50.71 +/- 8.2)%. The ethyl acetate fraction exhibited the highest level of AChE inhibition, followed by the dichloromethane fraction. The isolated alkaloid uleine displayed an IC50 value of 0.45 microM.

A prevalência de fatores de risco para doenças cardiovasculares em estudantes universitários / Prevalence of risk factors for cardiovascular disease in students

JUSTIFICATIVA E OBJETIVOS: As doenças cardiovasculares constituem um grave problema de saúde pública no Brasil e no Mundo, responsáveis por aproximadamente 15 milhões de óbitos, representando os mais altos custos em assistência médica. O objetivo deste estudo foi verificar a existência de fatores de risco para doenças cardiovasculares em estudantes universitários do Centro Universitário Lusíada. MÉTODO: Trata-se de um estudo quantitativo explorativo descritivo, em que foram avaliados 90 indivíduos, submetidos à um questionário contendo os principais fatores de risco para doenças cardiovasculares e a aferição da pressão arterial, frequência cardíaca, frequência respiratória e a mensuração da altura e do peso. RESULTADOS: Os principais fatores de risco para doenças cardiovasculares encontrados foram antecedentes familiares, em 66,67% dos entrevistados; sedentarismo, em 44% e o sobrepeso (índice de massa corpórea 25-30 kg/m2) em 24,44%. CONCLUSÃO: O estudo demonstrou significância, onde os principais fatores de risco para doenças cardiovasculares foram antecedentes familiares, sedentarismo e sobrepeso. O reconhecimento do perfil dos universitários em relação a esses fatores de risco torna-se importante, para que sejam traçadas medidas preventivas.