In Vitro and in Vivo Antimalarial Activity, Cytotoxicity and Phytochemical HRMS2 Profile of Plants from the Western Pará State, Brazilian Amazonia.

Ethnopharmacology and botanical taxonomy are valid criteria used to selecting plants for antimalarial bioprospection purposes. Based on these two criteria, ethanol extracts of 11 plants from Santarém City vicinities, Western Pará State, Brazilian Amazonia, had their in vitro antiplasmodial activity against chloroquine-resistant Plasmodium falciparum (W2 clone) assessed by the PfLDH method, whereas their cytotoxicity to HepG2-A16 cells was assessed through MTT assay. Acmella oleracea, Siparuna krukovii and Trema micrantha extracts disclosed the highest rate of parasite growth inhibition (90 %) in screening tests. In vivo antimalarial assays were conducted with these extracts against Plasmodium berghei (NK 65 strain) infected mice. Inhibition rate of parasite multiplication ranged from 41.4 % to 60.9 % at the lowest extract dose (25 mg/kg). HPLC-ESI-HRMS2 analyses allowed the putative identification of alkylamides, fatty acids, flavonoid glycosides and alkaloids in ethanol extracts deriving from these three plant species. Results pointed towards A. oleracea flowers ethanol extract as the most promising potential candidate to preclinical studies aiming the development of antimalarial phytomedicine.

Brazilian plants with antimalarial activity: A review of the period from 2011 to 2022.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria continues to be a serious global public health problem in subtropical and tropical countries of the world. The main drugs used in the treatment of human malaria, quinine and artemisinin, are isolates of medicinal plants, making the use of plants a widespread practice in countries where malaria is endemic. Over the years, due to the increased resistance of the parasite to chloroquine and artemisinin in certain regions, new strategies for combating malaria have been employed, including research with medicinal plants. AIM: This review focuses on the scientific production regarding medicinal plants from Brazil whose antimalarial activity was evaluated during the period from 2011 to 2022. 2. METHODOLOGY: For this review, four electronic databases were selected for research: Pubmed, ScienceDirect, Scielo and Periódicos CAPES. Searches were made for full texts published in the form of scientific articles written in Portuguese or English and in a digital format. In addition, prospects for new treatments as well as future research that encourages the search for natural products and antimalarial derivatives are also presented. RESULTS: A total of 61 publications were encountered, which cited 36 botanical families and 92 species using different Plasmodium strains in in vitro and in vivo assays. The botanical families with the most expressive number of species found were Rubiaceae, Apocynaceae, Fabaceae and Asteraceae (14, 14, 9 and 6 species, respectively), and the most frequently cited species were of the genera Psychotria L. (8) and Aspidosperma Mart. (12), which belong to the families Rubiaceae and Apocynaceae. Altogether, 75 compounds were identified or isolated from 28 different species, 31 of which are alkaloids. In addition, the extracts of the analyzed species, including the isolated compounds, showed a significant reduction of parasitemia in P. falciparum and P. berghei, especially in the clones W2 CQ-R (in vitro) and ANKA (in vivo), respectively. The Brazilian regions with the highest number of species analyzed were those of the north, especially the states of Pará and Amazonas, and the southeast, especially the state of Minas Gerais. CONCLUSION: Although many plant species with antimalarial potential have been identified in Brazil, studies of new antimalarial molecules are slow and have not evolved to the production of a phytotherapeutic medicine. Given this, investigations of plants of traditional use and biotechnological approaches are necessary for the discovery of natural antimalarial products that contribute to the treatment of the disease in the country and in other endemic regions.

Pharmacological Treatment of Alcohol Cravings.

(1) Background: The treatment of substance addiction is challenging and has persisted for decades, with only a few therapeutic options. Although there are some recommendations for specific treatments for Alcohol Use Disorder (AUD), there is no specific medication used to treat alcohol cravings, which could benefit millions of patients that are suffering from alcoholism. Cravings, or the urge to use drugs, refer to the desire to experience the effects of a previously experienced psychoactive substance. (2) Methods: We included original studies of alcohol abuse or dependence extracted from a controlled, blind, pharmacological treatment study which presented measures and outcomes related to alcohol cravings. (3) Results: Specific drugs used for the treatment of alcoholism, such as Naltrexone and Acamprosate, have had the best results in relieving craving symptoms, as well as promoting abstinence. Baclofen and anticonvulsants such as Gabapentin and Topiramate have shown good results in promoting abstinence and the cessation of cravings. (4) Conclusions: Specific drugs used for the treatment of alcoholism to obtain the best results can be considered the gold standard for promoting abstinence and relieving cravings. Anticonvulsants and Baclofen also had good results, with these medications being considered as second-line ones. Varenicline is an option for alcohol dependents who also concomitantly ingest tobacco.

RECURRENT SEPSIS IN A PATIENT WITH BILIARY HAMARTOMAS.

Biliary hamartomas or von Meyenburg complexes (VMCs) are hepatic tumour-like lesions related to congenital malformation of the ductal plate, and are part of the ciliopathy spectrum of disorders. The exact pathogenesis of VMCs is unclear and it remains controversial whether they have the potential for malignant transformation. Patients are often asymptomatic and VMCs are usually encountered as an incidental finding on imaging. We report a case of recurrent sepsis with an unidentified focus. It was later confirmed that biliary hamartomas were acting as a sanctuary for the persistent pathogenic agent. The authors hope to draw attention to the existence of this unusual focus of recurrent sepsis. LEARNING POINTS: Hepatobiliary sepsis is an unusual clinical presentation of biliary hamartomas.Clinicians should be aware of the infectious complications of these diffuse structural biliary ductal abnormalities.Early recognition of this atypical life-threatening clinical presentation is important for the prognosis.

Clinical and Epidemiological Features of Hospitalized and Ambulatory Patients with Human Monkeypox Infection: A Retrospective Observational Study in Portugal.

Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Ceftriaxone-induced Agranulocytosis.

Ceftriaxone is a widely used antibiotic regarded as safe and effective. Drug-induced agranulocytosis is a life-threatening adverse reaction and few reports related to ceftriaxone were found in a review of the literature. The authors present a case of ceftriaxone-induced agranulocytosis, in which a brain abscess was diagnosed and ceftriaxone was commenced. Neutropenic fever occurred on the 29th day of therapy with a cumulative dose of 116 g ceftriaxone and a neutrophil nadir of 0.1×109/l. Ceftriaxone was withheld, filgrastim was administered for 3 days and neutrophil normalization was achieved. Although rare, ceftriaxone-induced agranulocytosis may occur in patients on a long course of ceftriaxone therapy. Prompt recognition and drug withdrawal are required. LEARNING POINTS: Ceftriaxone-induced agranulocytosis is rare but may occur in patients with high cumulative doses.Prompt recognition, drug withdrawal and administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are the mainstay approach.

Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions.

BACKGROUND: Except for the northern region, where the Amazonian black scorpion, T. obscurus, represents the predominant and most medically relevant scorpion species, Tityus serrulatus, the Brazilian yellow scorpion, is widely distributed throughout Brazil, causing most envenoming and fatalities due to scorpion sting. In order to evaluate and compare the diversity of venom components of Tityus obscurus and T. serrulatus, we performed a transcriptomic investigation of the telsons (venom glands) corroborated by a shotgun proteomic analysis of the venom from the two species. RESULTS: The putative venom components represented 11.4% and 16.7% of the total gene expression for T. obscurus and T. serrulatus, respectively. Transcriptome and proteome data revealed high abundance of metalloproteinases sequences followed by sodium and potassium channel toxins, making the toxin core of the venom. The phylogenetic analysis of metalloproteinases from T. obscurus and T. serrulatus suggested an intraspecific gene expansion, as we previously observed for T. bahiensis, indicating that this enzyme may be under evolutionary pressure for diversification. We also identified several putative venom components such as anionic peptides, antimicrobial peptides, bradykinin-potentiating peptide, cysteine rich protein, serine proteinases, cathepsins, angiotensin-converting enzyme, endothelin-converting enzyme and chymotrypsin like protein, proteinases inhibitors, phospholipases and hyaluronidases. CONCLUSION: The present work shows that the venom composition of these two allopatric species of Tityus are considerably similar in terms of the major classes of proteins produced and secreted, although their individual toxin sequences are considerably divergent. These differences at amino acid level may reflect in different epitopes for the same protein classes in each species, explaining the basis for the poor recognition of T. obscurus venom by the antiserum raised against other species.

Operando monitoring the nanometric morphological evolution of TiO2 nanoparticles in a Na-ion battery.

Na-ion batteries are nowadays receiving renewed attention because of its propitiousness for large-scale stationary applications. Although the Na storage mechanism is still not completely understood, TiO2 nanoparticles are very promising active anode materials in Na-ion batteries provided that a correct dispersion is achieved within the battery electrode. Whilst the structural changes, either in crystallinity or crystalline phase, that occur during operation are receiving much recent attention, the nanometric morphological evolution of the TiO2 nanoparticles within the electrode is yet to be thoroughly addressed, despite its implication in battery efficiency. In the present work, operando small-angle x-ray scattering studies on TiO2/Na-ion batteries show that whereas the nanoparticle size is preserved during the discharge-charge cycles, the mean distance between nanoparticles increases. The observed morphological changes are consistent with electrode swelling and nanoparticle aggregation during operation, being one phenomenon dominant over the other depending on the applied density current; thus, depending on the differences in ion diffusion within the electrode.

Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions

Background Except for the northern region, where the Amazonian black scorpion, T. obscurus, represents the predominant and most medically relevant scorpion species, Tityus serrulatus, the Brazilian yellow scorpion, is widely distributed throughout Brazil, causing most envenoming and fatalities due to scorpion sting. In order to evaluate and compare the diversity of venom components of Tityus obscurus and T. serrulatus, we performed a transcriptomic investigation of the telsons (venom glands) corroborated by a shotgun proteomic analysis of the venom from the two species. Results The putative venom components represented 11.4% and 16.7% of the total gene expression for T. obscurus and T. serrulatus, respectively. Transcriptome and proteome data revealed high abundance of metalloproteinases sequences followed by sodium and potassium channel toxins, making the toxin core of the venom. The phylogenetic analysis of metalloproteinases from T. obscurus and T. serrulatus suggested an intraspecific gene expansion, as we previously observed for T. bahiensis, indicating that this enzyme may be under evolutionary pressure for diversification. We also identified several putative venom components such as anionic peptides, antimicrobial peptides, bradykinin-potentiating peptide, cysteine rich protein, serine proteinases, cathepsins, angiotensin-converting enzyme, endothelin-converting enzyme and chymotrypsin like protein, proteinases inhibitors, phospholipases and hyaluronidases. Conclusion The present work shows that the venom composition of these two allopatric species of Tityus are considerably similar in terms of the major classes of proteins produced and secreted, although their individual toxin sequences are considerably divergent. These differences at amino acid level may reflect in different epitopes for the same protein classes in each species, explaining the basis for the poor recognition of T. obscurus venom by the antiserum raised against other species.

Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions

Background Except for the northern region, where the Amazonian black scorpion, T. obscurus, represents the predominant and most medically relevant scorpion species, Tityus serrulatus, the Brazilian yellow scorpion, is widely distributed throughout Brazil, causing most envenoming and fatalities due to scorpion sting. In order to evaluate and compare the diversity of venom components of Tityus obscurus and T. serrulatus, we performed a transcriptomic investigation of the telsons (venom glands) corroborated by a shotgun proteomic analysis of the venom from the two species. Results The putative venom components represented 11.4% and 16.7% of the total gene expression for T. obscurus and T. serrulatus, respectively. Transcriptome and proteome data revealed high abundance of metalloproteinases sequences followed by sodium and potassium channel toxins, making the toxin core of the venom. The phylogenetic analysis of metalloproteinases from T. obscurus and T. serrulatus suggested an intraspecific gene expansion, as we previously observed for T. bahiensis, indicating that this enzyme may be under evolutionary pressure for diversification. We also identified several putative venom components such as anionic peptides, antimicrobial peptides, bradykinin-potentiating peptide, cysteine rich protein, serine proteinases, cathepsins, angiotensin-converting enzyme, endothelin-converting enzyme and chymotrypsin like protein, proteinases inhibitors, phospholipases and hyaluronidases. Conclusion The present work shows that the venom composition of these two allopatric species of Tityus are considerably similar in terms of the major classes of proteins produced and secreted, although their individual toxin sequences are considerably divergent. These differences at amino acid level may reflect in different epitopes for the same protein classes in each species, explaining the basis for the poor recognition of T. obscurus venom by the antiserum raised against other species.

Prevalence and correlates of cannabis use among athletes-A systematic review.

BACKGROUND AND OBJECTIVES: Despite scientific evidence that marijuana impairs performance and mental health, there is evidence that some athletes are at higher risk for use. This review aims to identify possible risk factors associated with marijuana use in athletes. METHODS: A search was conducted in the PubMed database with the keywords: (marijuana OR cannabis OR tetrahydrocannabinol OR delta-9-tetrahydrocannabinol OR THC) AND (sports OR sport OR athlete OR athletes). We retrieved 186 studies. After applying the inclusion/exclusion criteria, 15 studies remained for review. RESULTS: The review revealed a number of potential risk factors for marijuana use among adult athletes, including being male, Caucasian, using sport performance-enhancing drugs, using marijuana to enhance recreation or non-sport performance, and practicing specific types of sports including skeleton, bobsleding, and ice hockey. Contrary to use patterns in the general population, among athletes marijuana appears to take the place of tobacco as the second most widely used drug, after alcohol. Many elite athletes denied the use of marijuana, which suggests that toxicological testing is an important tool for identifying users, because it is more accurate than self-report. Geography appears important, as in areas of high consumption, prevalence among athletes appears to be greater as well. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Contrary to the image that athletes do not use psychoactive drugs, this review suggests that a number of athletic subgroups are at increased risk for marijuana use. Surprisingly, a common rationale for use appears to be to enhance sports performance. As in the general population, experimentation starts early-in pre-adolescence-at an age that prevention and guidance programs could have positive influences. (Am J Addict 2016;25:518-528).

Estudo comparativo das proteínas de alto peso molecular de veneno de escorpiões de interesse médico do Brasil

Os escorpiões do gênero Tityus são amplamente distribuídos no Brasil, seu veneno é constituído por uma complexa mistura de toxinas: proteínas de alta massa molecular (PM > 10 kDa), peptídeos (PM 3-10) e componentes de baixa massa molecular (PM 14 kDa) do veneno de três espécies de escorpiões do gênero Tityus : Tityus serrulatus (Ts), Tityus bahiensis (Tb) e Tityus obscurus (To). Os venenos dos escorpiões Ts, Tb e To foram obtidos no Laboratório de Artrópodes do Instituto Butantan. As proteínas dos venenos foram separadas por SDS-PAGE 1-DE e 2-DE e as densidades das bandas ou spots foram quantificados pelo programa Quantity One e Image Master Platinum, respectivamente.

Importance of cancer among the Brazilian elderly population from 2000 to 2005 / A importância das neoplasias na população idosa brasileira de 2000 a 2005

Objective: To describe cancer hospital morbidity and mortality in the Brazilian elderly population according to the primary site of neoplasms per Brazilian region and their importance on Public Health System expenses. Methods: The data were obtained from the Ministry of Health records from 2000 to 2005. Results: From 2000 to 2005, there were 507,174 deaths due to neoplasms of the population older than 60 years old. The largest mortality rates were found in South and South-East regions. Among women, breast cancer was the most fatal neoplasm; among men, prostate cancer and trachea, bronchi and lung cancer. In situ neoplasms accounted for the highest average hospitalizations and the highest average expenses of the total amount paid for hospitalizations, while brain neoplasms accounted for the highest average amount spent per hospitalization. Conclusions: The elderly population corresponds to the majority of deaths due to neoplasms in the Brazilian population and for most of the hospitalizations expenses due to oncologic causes and subsequent expenses of the public health system.

Objetivo: Descrever a mortalidade e a morbidade hospitalar por câncer em idosos no Brasil de acordo com o sítio primário das neoplasias por regiões do Brasil e o valor gasto no Sistema Público de Saúde. Métodos: Os dados foram obtidos dos registros do Ministério da Saúde, no Sistema de Informação sobre Mortalidade (SIM) e Sistema de Informação Hospitalar (SIH) no período de 2000 a 2005. Resultados: Nos anos de 2000 a 2005 ocorreram 507.174 óbitos por neoplasias em pessoas com mais de 60 anos. As maiores taxas de mortalidade foram encontradas nas regiões Sul e Sudeste. Entre as mulheres, o câncer de mama foi a neoplasia que apresentou maior mortalidade e, entre os homens, foi o câncer de próstata e o de traqueia, brônquios e pulmão. As neoplasias in situ apresentaram a maior média de internações e a maior média anual do valor total pago em internações enquanto as neoplasias de encéfalo apresentaram o maior valor médio gasto em reais por internação. Conclusões: A população geriátrica corresponde à maior parcela dos óbitos por neoplasia na população brasileira e por grande parte dos gastos em internações por causa oncológica e consequentes gastos com o sistema de saúde público.

[Analysis of delays in diagnosis and treatment of breast cancer patients at a public hospital]. / Análise do atraso no diagnóstico e tratamento do câncer de mama em um hospital público.

BACKGROUND: To identify potential delays in the management of patients with breast cancer examined at a public hospital, from time of suspicion until diagnosis and beginning of treatment. METHODS: Retrospective study which analyzed data related to time elapsed in different intervals between suspicion, diagnosis and onset of systemic cancer-directed treatments, of consecutive breast cancer patients cared for at the medical oncology clinic of the Mario Covas Hospital during 2006. RESULTS: Sixty-eight women, with a mean age of 56.3 years (standard deviation: 12.2 years), were included. Of all the intervals, the longest delay occurred between the mammographic suspicion of cancer and performance of biopsy (median of 72 days, range: 4 - 1095 days); this was significantly longer (P<0.001) than in the other intervals analyzed. Furthermore, this interval in particular, was significantly longer in patients with advanced stage breast cancer when compared to those at the initial stage (P=0.014). CONCLUSION: Breast cancer patients treated in a public hospital in Brazil suffer delays, especially during the diagnosis of their disease. Minimizing the time between mammography and biopsy of suspicious lesions appears to be the most critical step to correct this situation.

Análise do atraso no diagnóstico e tratamento do câncer de mama em um hospital público / Analysis of delays in diagnosis and treatment of breast cancer patients at a public hospital

OBJETIVO: Identificar as possíveis fases de atraso na condução de pacientes com câncer de mama atendidas em um hospital público, desde a suspeita até o diagnóstico e o início do tratamento. MÉTODOS: Estudo retrospectivo, no qual foram analisados em pacientes com câncer de mama atendidas consecutivamente no Serviço de Oncologia do Hospital Estadual Mário Covas, durante o ano de 2006, os dados relativos aos intervalos de tempo transcorrido entre a suspeita, o diagnóstico e o início do tratamento adjuvante sistêmico. RESULTADOS: Sessenta e oito mulheres foram incluídas. A média de idade foi de 56,3 anos (desvio padrão: 12,2 anos). Entre os intervalos analisados, o maior atraso ocorreu entre a suspeita mamográfica de câncer e a realização da biópsia (mediana de 72 dias, variação de 4 a 1095 dias), sendo este significativamente maior (p<0,001) quando comparado aos demais intervalos analisados. Além disso, considerando particularmente este intervalo, verifica-se que foi significativamente maior nas pacientes com câncer de mama de estadio avançado, comparativamente àquelas de estadio inicial (p=0,014). CONCLUSÃO: Pacientes com câncer de mama tratadas em serviço público sofrem atrasos importantes, principalmente no período de diagnóstico de sua doença. Com base em nossos dados, otimizar o intervalo entre a mamografia e a obtenção da biópsia de lesões suspeitas parece ser a estratégia mais profícua.

BACKGROUND: To identify potential delays in the management of patients with breast cancer examined at a public hospital, from time of suspicion until diagnosis and beginning of treatment. METHODS: Retrospective study which analyzed data related to time elapsed in different intervals between suspicion, diagnosis and onset of systemic cancer-directed treatments, of consecutive breast cancer patients cared for at the medical oncology clinic of the Mario Covas Hospital during 2006. RESULTS: Sixty-eight women, with a mean age of 56.3 years (standard deviation: 12.2 years), were included. Of all the intervals, the longest delay occurred between the mammographic suspicion of cancer and performance of biopsy (median of 72 days, range: 4 - 1095 days); this was significantly longer (P<0.001) than in the other intervals analyzed. Furthermore, this interval in particular, was significantly longer in patients with advanced stage breast cancer when compared to those at the initial stage (P=0.014). CONCLUSION: Breast cancer patients treated in a public hospital in Brazil suffer delays, especially during the diagnosis of their disease. Minimizing the time between mammography and biopsy of suspicious lesions appears to be the most crintical step to correct this situation.