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BACKGROUND: Use of intravascular ultrasound (IVUS) during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes over angiography alone. Despite this, the adoption of IVUS in clinical practice remains low. AIMS: To examine the cost-effectiveness of IVUS-guided PCI compared to angiography alone in patients with acute coronary syndromes (ACS). METHODS: A one-year decision tree and lifetime Markov model were constructed to compare the cost-effectiveness of IVUS-guided PCI to angiography alone for two hypothetical adult populations consisting of 1,000 individuals: ST-elevation myocardial infarction (STEMI) and unstable angina/ non-ST-elevation myocardial infarction (UA/NSTEMI) patients undergoing drug-eluting stent (DES) implantation. The UK healthcare system perspective was applied using 2019/20 costs. All-cause death, myocardial infarction (MI), repeat PCI, lifetime costs, life expectancy and quality-adjusted life-years (QALYs) were assessed. RESULTS: Over a lifetime horizon, IVUS-guided PCI was cost-effective compared to angiography alone in both populations, yielding an incremental cost-effectiveness ratio of £3,649 and £5,706 per-patient in STEMI and UA/NSTEMI patients, respectively. In the one-year time horizon, the model suggested that IVUS was associated with reductions in mortality, MI and repeat PCI by 51%, 33% and 52% in STEMI and by 50%, 29% and 57% in UA/NSTEMI patients, respectively. Sensitivity analyses demonstrated the robustness of the model with IVUS being 100% cost-effective at a willingness-to-pay (WTP) threshold of £20,000 per QALY-gained. CONCLUSIONS: From a UK healthcare perspective, an IVUS-guided PCI strategy was highly cost-effective over angiography alone amongst ACS patients undergoing DES implantation due to the medium- and long-term reduction in repeat PCI, death, and MI.
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PeRsOnalised Integrated CARE Solution for Elderly (PROCare4Life) was an EU-funded project that ran from January 2020 until June 2023, whose focus was to further develop and integrate previous ICT solutions developed by several previous EU-funded projects into a unique modular system able to support the autonomy and empowerment and to increase the Quality of Life (QoL) of elderly people living with Parkinson's, Alzheimer's, or similar dementia, having also tested the system for elderly people living with comorbidities. This article focuses on the methodology and results used to identify the internal lessons learned. PROCare4Life was developed using a codesign approach involving more than 2,000 participants whose input has been listened to and transformed into valuable changes of the system and also into lessons learned included in this case study report. Since the beginning of the implementation of PROCare4Life, there has been a commitment to make invisible knowledge visible through open discussion and including our lessons learned in each of our deliverables. In the last six months of implementation, qualitative research has been implemented by the PROCare4Life consortium to identify and select our most relevant challenges and recommendations for future projects and initiatives. PROCare4Life was highly impacted by the COVID-19 pandemic, and it is acknowledged in the lessons learned. However, the consortium has focused on the recommendations that could be more valuable for ordinary implementation of future projects and initiatives developing eHealth tools for elderly citizens living with conditions that might affect their cognitive or mobility capacities.
PeRsOnalised Integrated CARE Solution for Elderly (PROCare4Life) was an EU-funded project that ran from January 2020 until June 2023, aiming at improving the quality of life of older people living with Parkinson's, Alzheimer's or other dementia using ICT technologies. The term implementation refers to the process of putting a plan or idea into action. It is a complex process that involves multiple stages, including planning, execution, and evaluation. Implementation research is a growing field of health research that aims to study the factors that affect the implementation of health policies, programs, and practices. It can help identify the best strategies for introducing potential solutions into a health system or promoting their large-scale use and sustainability. For PROCare4Life, when using the term implementation it covers all the stages, including ideation and design phases, although focusing on the pilot 3 iterative codesign and testing of the system. Using daily life devices such as smartphones and smart watches, more than 2,000 people have contributed to co-creating PROCare4Life. The three profiles focused on were older people living with Parkinson's, Alzheimer's or other dementia, their main carers and their healthcare professionals, with an ICT system providing direct communication and allowing them to share their health status. Along the journey to develop PROCare4Life, our European consortium has learned many things that we have internally investigated and reported in this article. We have identified 20 challenges and 41 recommendations. We hope that our lessons learned might be inspiring and valuable for others, particularly future projects and initiatives developing eHealth tools for elderly EU citizens living with different conditions that might affect their cognitive or mobility capabilities.
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Bothrops asper is one of the most important snake species in Central America, mainly because of its medical importance in countries like Ecuador, Panama and Costa Rica, where this species causes a high number of snakebite accidents. Several basic phospholipases A2 (PLA2s) have been previously characterized from B. asper venom, but few studies have been carried out with its acidic isoforms. In addition, since snake venom is a rich source of bioactive substances, it is necessary to investigate the biotechnological potential of its components. In this context, this study aimed to carry out the biochemical characterization of PLA2 isoforms isolated from B. asper venom and to evaluate the antiparasitic potential of these toxins. The venom and key fractions were subjected to different chromatographic steps, obtaining nine PLA2s, four acidic ones (BaspAc-I, BaspAc-II, BaspAc-III and BaspAc-IV) and five basic ones (BaspB-I, BaspB-II, BaspB-III, BaspB-IV and BaspB-V). The isoelectric points of the acidic PLA2s were also determined, which presented values ranging between 4.5 and 5. The findings indicated the isolation of five unpublished isoforms, four Asp49-PLA, corresponding to the group of acidic isoforms, and one Lys49-PLA2-like. Acidic PLA2s catalyzed the degradation of all substrates evaluated; however, for the basic PLA2s, there was a preference for phosphatidylglycerol and phosphatidic acid. The antiparasitic potential of the toxins was evaluated, and the acidic PLA2s demonstrated action against the epimastigote forms of T. cruzi and promastigote forms of L. infantum, while the basic PLA2s BaspB-II and BaspB-IV showed activity against P. falciparum. The results indicated an increase of up to 10 times in antiplasmodial activity, when the Asp49-PLA2 and Lys49-PLA2 were associated with one another, denoting synergistic action between these PLA2 isoforms. These findings correspond to the first report of synergistic antiplasmodial action for svPLA2s, demonstrating that these molecules may be important targets in the search for new antiparasitic agents.
Assuntos
Antiprotozoários/farmacologia , Fosfolipases A2/química , Plasmodium falciparum/efeitos dos fármacos , Venenos de Serpentes/metabolismo , Sequência de Aminoácidos , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Bothrops/metabolismo , Sinergismo Farmacológico , Ponto Isoelétrico , Leishmania infantum/efeitos dos fármacos , Panamá , Testes de Sensibilidade Parasitária , Fosfolipases A2/isolamento & purificação , Fosfolipases A2/farmacologia , Isoformas de Proteínas/química , Isoformas de Proteínas/isolamento & purificação , Isoformas de Proteínas/farmacologia , Alinhamento de SequênciaRESUMO
Leishmaniasis is considered a neglected disease, which makes it an unattractive market for the pharmaceutical industry; hence, efforts in the search for biologically active substances are hampered by this lack of financial motivation. Thus, in the present study, we report the leishmanicidal activity and the possible mechanisms of action of compounds with promising activity against the species Leishmania (V.) braziliensis, the causative agent of the skin disease leishmaniasis. The natural compound 1a (piplartine) and the analog 2a were the most potent against promastigote forms with growth inhibition values for 50% of the parasite population (IC50) = 8.58 and 11.25 µM, respectively. For amastigote forms, the ICa50 values were 1.46 and 16.7 µM, respectively. In the molecular docking study, piplartine showed favorable binding energy (-7.13 kcal/mol) and with 50% inhibition of trypanothione reductase (IC50) = 91.1 µM. Preliminary investigations of the mechanism of action indicate that piplartine increased ROS levels, induced loss of cell membrane integrity, and caused accumulation of lipid bodies after 24 h of incubation at its lowest effective concentration (IC50), which was not observed for the synthetic analog 2a. The mode of action for the leishmanicidal activity of piplartine (1a) was assigned to involve affinity for the trypanothione reductase of Leishmania (V.) braziliensis TR.
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Amidas/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Piperidonas/farmacologia , Tripanossomicidas/farmacologia , Amidas/química , Animais , Linhagem Celular Tumoral , Chlorocebus aethiops , Simulação por Computador , Humanos , Simulação de Acoplamento Molecular , NADH NADPH Oxirredutases/antagonistas & inibidores , Piperidonas/química , Células VeroRESUMO
Scientific advances in nanotechnology and nanoscience have enabled stability optimization and signal amplification in immunoassays by taking advantage of unique properties of nanomaterials. Biosensors based on antibodies and their fragments, also called immunosensors, are compact tools capable of providing refined antigen detection capacity. Different immunoassays that utilize these molecules for biorecognition have been used as diagnostic tools. In this regard, camelid single domain antibodies fulfill several requirements, such as nanometric size, high affinity, specificity, solubility, stability, biotechnological versatility, and low cost of production, constituting an important source for the development of immunodiagnostic devices. In this review, the main technological advances involving this specific class of molecules, as well as their major biotechnological applications will be addressed, with emphasis on their use as biosensors applied to diagnostics in human health.
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Técnicas Biossensoriais/instrumentação , Técnicas e Procedimentos Diagnósticos , Imunoensaio/instrumentação , Anticorpos de Domínio Único/metabolismo , Saúde , Humanos , MedicinaRESUMO
Malaria is a parasitic infectious disease and was responsible for 400.000 deaths in 2018. Plasmodium falciparum represents the species that causes most human deaths due to severe malaria. In addition, studies prove the resistance of P. falciparum to drugs used to treat malaria, making the search for new drugs with antiplasmodial potential necessary. In this context, the literature describes snake venoms as a rich source of molecules with microbicidal potential, including phospholipases A2 (PLA2s). In this sense, the present study aimed to isolate basic PLA2s from Paraguayan Bothrops diporus venom and evaluate their antiplasmodial potential. Basic PLA2s were obtained using two chromatographic steps. Initially, B. diporus venom was subjected to ion exchange chromatography (IEC). The electrophoretic profile of the fractions from the IEC permitted the selection of 3 basic fractions, which were subjected to reverse phase chromatography, resulting in the isolation of the PLA2s. The toxins were tested for enzymatic activity using a chromogenic substrate and finally, the antiplasmodial, cytotoxic potential and hemolytic activity of the isolated toxins were evaluated. The electrophoretic profile of the fractions from the IEC permitted the selection of 3 basic fractions, which were subjected to reverse phase chromatography, resulting in the isolation of the two enzymatically active PLA2s, BdTX-I and BdTX-II and the PLA2 homologue BdTX-III. The antiplasmodial potential was evaluated and the toxins showed IC50 values of: 2.44, 0.0153 and 0.59 µg/mL respectively, presenting PLA2 selectivity according to the selectivity index results (SI) calculated against HepG2 cells. The results show that the 3 basic phospholipases isolated in this study have a potent antiparasitic effect against the W2 strain of P. falciparum. In view of the results obtained in this work, further research are necessary to determine the mechanism of action by which these toxins cause cell death in parasites.
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The complete knowledge of the toxins that make up venoms is the base for the treatment of snake accidents victims and the selection of specimens for the preparation of venom pools for antivenom production. In this work, we used a fast and direct venomics approach to identify the toxin families in the C.d. terrificus venom, a Southern American Neotropical rattlesnake. The RP-HPLC separation profile of pooled venom from adult specimens followed by mass spectrometry analysis revealed that C.d. terrificus' venom proteome is composed of 12 protein families, which are unevenly distributed in the venom, e.g., there are few major proteins in the venom's composition phospholipase A2, serine proteinase, crotamine and L-amino acid oxidase. At the same time, the proteome analysis revealed a small set of proteins with low quantity (less than 1.5%), both enzymes (metaloprotease, phospholipase B and 5'-nucleotidase) and proteins (Bradykinin potentiating and C-type natriuretic peptides, C-type lectin convulxin and nerve growth factor). To sum up, this research is the first venomic report of C.d.terrificus venom from Argentina. This proved to be crotamine positive venom that has a lower metalloprotease content than C.d. terrificus venoms from other regions. This information could be used in the discovery of future pharmacological agents or targets in antivenom therapy.
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BACKGROUND: The aim of the study was to evaluate the performance of "Acute Physiology and Chronic Health Evaluation II" (APACHE-II), "Simplified Acute Physiology Score 3" (SAPS-3), and "APACHE-II Score for Critically Ill Patients with a Solid Tumor" (APACHE-IICCP) models in cancer patients admitted to ICU. METHODS: Prospective cohort study of 414 patients with an active solid tumor. Discrimination was assessed by area under receiver operating characteristic (AROC) curves and calibration by Hosmer-Lemeshow goodness-of-fit C test (H-L). RESULTS: The hospital mortality rate was 32.6%. In the total cohort, discrimination for prognostic models were: APACHE-IICCP (AROC 0.98), APACHE-II (AROC 0.96), SAPS-3 for Central and South American countries (SAPS-3CSA) (AROC 0.95), and SAPS-3 (AROC 0.91). Calibration was good (p value of H-L test > 0.05) using APACHE-IICCP, APACHE-II and SAPS-3CSA models. Estimation of the probability of death was more precise with APACHE-IICCP (standardized mortality ratio, SMR = 1.03) and SAPS-3 (SMR = 1.08) models. Further analysis showed that discrimination was high with all prognostic model whether for patients with planned ICU admission (AROC APACHE-IICCP 0.97, APACHE-II 0.96, SAPS-3 0.95, SAPS-3CSA 0.95) or for patients with unplanned ICU admission (AROC APACHE-IICCP 0.97, APACHE-II 0.94, SAPS-3 0.86, SAPS-3CSA 0.95). Calibration was good for all predictive models in both subgroups (p value of H-L test > 0.05, except for APACHE-II model inpatients with planned ICU admission). CONCLUSIONS: In this prospective study, general predictive models (e.g., APACHE-II, SAPS-3) and cancer-specific models (e.g., APACHE-IICCP) are accurate in predicting hospital mortality. Other studies confirming these results are required.
Assuntos
APACHE , Modelos Estatísticos , Neoplasias/etiologia , Neoplasias/mortalidade , Idoso , Área Sob a Curva , Estado Terminal/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROCRESUMO
BACKGROUND: Functional and structural diversity of proteins of snake venoms is coupled with a wide repertoire of pharmacological effects. Snake venoms are targets of studies linked to searching molecules with biotechnological potential. METHODS: A homologue phospholipase A2 (BmatTX-IV) was obtained using two chromatographic techniques. Mass spectrometry and two-dimensional gel electrophoresis were used to determine the molecular mass and isoelectric point, respectively. By means of Edman degradation chemistry, it was possible to obtain the partial sequence of amino acids that comprise the isolated toxin. Trypanocidal, leishmanicidal and cytoxic activity against Trypanosoma cruzi, Leishmania infantum and murine fibrobasts was determinated. RESULTS: Combination of both chromatographic steps used in this study demonstrated efficacy to obtain the PLA2-Lys49. BmatTX-IV showed molecular mass and isoelectric point of 13.55 kDa and 9.3, respectively. Amino acid sequence of N-terminal region (51 residues) shows the presence of Lys49 residue at position 49, a distinctive trait of enzymatically inactive PLA2. Bothrops mattogrossensis snake venom showed IC50 values of 11.9 µg/mL against Leishmania infantum promastigotes and of 13.8 µg/mL against Trypanosoma cruzi epimastigotes, respectively. On the other hand, the venom showed a high cytotoxic activity (IC50 value of 16.7 µg/mL) against murine fibroblasts, whereas the BmatTX-IV showed IC50 value of 81.2 µg/mL. CONCLUSION: Physicochemical and biological characterization of snake venoms components is critically important, since these complex mixtures provide a source of molecules with antiparasitic potential, making further studies necessary to identify and characterize components with higher efficacy and selectivity.
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Antiparasitários/farmacologia , Leishmania infantum/efeitos dos fármacos , Fosfolipases A2/farmacologia , Venenos de Serpentes/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiparasitários/química , Antiparasitários/isolamento & purificação , Bothrops , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Camundongos , Paraguai , Testes de Sensibilidade Parasitária , Fosfolipases A2/química , Fosfolipases A2/isolamento & purificação , Venenos de Serpentes/química , Venenos de Serpentes/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
There is a growing need for research on new antimalarial agents against Plasmodium falciparum infection, especially in regards to planning molecular architecture for specific molecular targets of the parasite. Thus, a metalloprotease from Bothrops moojeni, known as BmooMPα-I, was explored in this study, through in silico assays, aiming at the development of a peptide generated from this molecule with potential inhibitory action on PfPNP, an enzyme necessary for the survival of the parasite. In order to isolate BmooMPα-I, cation exchange and reverse phase chromatographies were performed, followed by in vitro assays of antiparasitic activity against the W2 strain of P. falciparum. The interactions between BmooMPα-I and PfPNP were evaluated via docking, and the resulting peptide, described as Pep1 BM, was selected according to the BmooMPα-I region demonstrating the best interaction score with the target of interest. The values for the specific activities of the PfPNP reaction were measured using the inorganic phosphate substrate and MESG. The fraction corresponding to BmooMPα-I was identified as fraction 4 in the cation exchange chromatography step, due to proteolytic activity on casein and the presence of a major band at â 23â¯kDa. BmooMPα-I was able to inhibit in vitro growth of W2 P. falciparum, with an IC50 value of 16.14⯵g/mL. Virtual screening with Pep1 BM demonstrated two PfPNP target binding regions, with ΔG values at the interaction interface of -10.75â¯kcal/mol and -11.74â¯kcal/mol. A significant reduction in the enzymatic activity of PfPNP was observed in the presence of Pep 1 BM when compared to the assay in the absence of this possible inhibitor. BmooMPα-I showed activity in vitro against W2 P. falciparum. By means of in silico techniques, the Pep 1 BM was identified as having potential binding affinity to the catalytic site of PfPNP and of inhibiting its catalytic activity in vitro.
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Antimaláricos/farmacologia , Venenos de Crotalídeos/enzimologia , Metaloendopeptidases/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Purina-Núcleosídeo Fosforilase/metabolismo , Animais , Antimaláricos/química , Bothrops/metabolismo , Domínio Catalítico , Venenos de Crotalídeos/química , Venenos de Crotalídeos/farmacologia , Cinética , Malária Falciparum/tratamento farmacológico , Metaloendopeptidases/química , Simulação de Acoplamento Molecular/métodos , Peptídeos/química , Especificidade por SubstratoRESUMO
BACKGROUND: Research involving snake venom has gradually surpassed the simple discovery of new molecules using purification and structural characterization processes, and extended to the identification of their molecular targets and the evaluation of their therapeutic potential. Nevertheless, this only became possible due to constant progress in experimental biology and protein purification approaches. OBJECTIVE: This review aims to discuss the main components of snake venoms that have been investigated for biotechnological purposes, and to discover how these promising biomolecules were obtained with the satisfactory degree of purity that have enabled such studies. Advances in purification technologies of various snake venom molecules have allowed for important discoveries of proteins and peptides with different biomedical and biotechnological applications. RESULT AND CONCLUSION: It is believed that significant experimental and computational advances will arise in similar proportions in the coming years that will allow researchers to map the molecular regions responsible for their pharmacological actions, their respective mechanisms of action and their cell targets.
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Venenos de Serpentes/química , Venenos de Serpentes/farmacologia , Serpentes/fisiologia , Animais , Descoberta de Drogas , Humanos , Proteínas/química , Venenos de Serpentes/genética , Venenos de Serpentes/uso terapêuticoRESUMO
Phospholipases A2 (PLA2s) are important enzymes present in snake venoms and are related to a wide spectrum of pharmacological effects, however the toxic potential and therapeutic effects of acidic isoforms have not been fully explored and understood. Due to this, the present study describes the isolation and biochemical characterization of two new acidic Asp49-PLA2s from Bothrops brazili snake venom, named Braziliase-I and Braziliase-II. The venom was fractionated in three chromatographic steps: ion exchange, hydrophobic interaction and reversed phase. The isoelectric point (pI) of the isolated PLA2s was determined by two-dimensional electrophoresis, and 5.2 and 5.3 pIs for Braziliase-I and II were observed, respectively. The molecular mass was determined with values ââof 13,894 and 13,869Da for Braziliase-I and II, respectively. Amino acid sequence by Edman degradation and mass spectrometry completed 87% and 74% of the sequences, respectively for Braziliase-I and II. Molecular modeling of isolated PLA2s using acid PLA2BthA-I-PLA2 from B. jararacussu template showed high quality. Both acidic PLA2s showed no significant myotoxic activity, however they induced significant oedematogenic activity. Braziliase-I and II (100µg/mL) showed 31.5% and 33.2% of cytotoxicity on Trypanosoma cruzi and 26.2% and 19.2% on Leishmania infantum, respectively. Braziliase-I and II (10µg) inhibited 96.98% and 87.98% of platelet aggregation induced by ADP and 66.94% and 49% induced by collagen, respectively. The acidic PLA2s biochemical and structural characterization can lead to a better understanding of its pharmacological effects and functional roles in snakebites pathophysiology, as well as its possible biotechnological applications as research probes and drug leads.
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Fosfolipases A2/química , Inibidores da Agregação Plaquetária/química , Agregação Plaquetária/efeitos dos fármacos , Venenos de Serpentes/química , Sequência de Aminoácidos/genética , Animais , Bothrops/genética , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/patogenicidade , Modelos Moleculares , Fosfolipases A2/genética , Fosfolipases A2/isolamento & purificação , Fosfolipases A2/farmacologia , Inibidores da Agregação Plaquetária/isolamento & purificação , Inibidores da Agregação Plaquetária/farmacologia , Homologia de Sequência de Aminoácidos , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/patogenicidadeRESUMO
Snake venoms contain various proteins, especially phospholipases A2 (PLA2s), which present potential applications in diverse areas of health and medicine. In this study, a new basic PLA2 from Bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. B. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. The isolated toxin, BmajPLA2-II, was structurally characterized with MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) mass spectrometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by two-dimensional electrophoresis, partial amino acid sequencing, an enzymatic activity assay, circular dichroism, and dynamic light scattering assays. These structural characterization tests presented BmajPLA2-II as a basic Lys49 PLA2 homologue, compatible with other basic snake venom PLA2s (svPLA2), with a tendency to form aggregations. The in vitro anti-parasitic potential of B. marajoensis venom and of BmajPLA2-II was evaluated against Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes, showing significant activity at a concentration of 100µg/mL. The venom and BmajPLA2-II presented IC50 of 0.14±0.08 and 6.41±0.64µg/mL, respectively, against intraerythrocytic forms of Plasmodium falciparum with CC50 cytotoxicity values against HepG2 cells of 43.64±7.94 and >150µg/mL, respectively. The biotechnological potential of these substances in relation to leishmaniasis, Chagas disease and malaria should be more deeply investigated.
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Antiprotozoários/química , Antiprotozoários/farmacologia , Bothrops , Venenos de Crotalídeos/enzimologia , Fosfolipases A2/química , Fosfolipases A2/farmacologia , Homologia de Sequência de Aminoácidos , Sequência de Aminoácidos , Animais , Antiprotozoários/metabolismo , Fosfolipases A2/metabolismo , Tripsina/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Toads belonging to genus Rhinella are used in Paraguayan traditional medicine to treat cancer and skin infections. AIM OF THE STUDY: The objective of the study was to determine the composition of venoms obtained from three different Paraguayan Rhinella species, to establish the constituents of a preparation sold in the capital city of Paraguay to treat cancer as containing the toad as ingredient, to establish the effect of the most active Rhinella schneideri venom on the cell cycle using human breast cancer cells and to assess the antiprotozoal activity of the venoms. METHODS: The venom obtained from the toads parotid glands was analyzed by HPLC-MS-MS. The preparation sold in the capital city of Paraguay to treat cancer that is advertised as made using the toad was analyzed by HPLC-MS-MS. The effect of the R. schneideri venom and the preparation was investigated on human breast cancer cells. The antiprotozoal activity was evaluated on Leishmania braziliensis, L. infantum and murine macrophages. RESULTS: From the venoms of R. ornata, R. schneideri and R. scitula, some 40 compounds were identified by spectroscopic and spectrometric means. Several minor constituents are reported for the first time. The preparation sold as made from the toad did not contained bufadienolides or compounds that can be associated with the toad but plant compounds, mainly phenolics and flavonoids. The venom showed activity on human breast cancer cells and modified the cell cycle proliferation. The antiprotozoal effect was higher for the R. schneideri venom and can be related to the composition and relative ratio of constituents compared with R. ornata and R. scitula. CONCLUSIONS: The preparation sold in the capital city of Paraguay as containing the toad venom, used popularly to treat cancer did not contain the toad venom constituents. Consistent with this, this preparation was inactive on proliferation of human breast cancer cells. In contrast, the toad venoms of Rhinella species altered the cell cycle progression, affecting the proliferation of malignant cells. The findings suggest that care should be taken with the providers of the preparation and that the crude drug present a strong activity towards human breast cancer cell lines. The antiprotozoal effect of the R. schneideri venom was moderate while the venom of R. ornata was devoid of activity and that of R. scitula was active at very high concentration.
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Venenos de Anfíbios/isolamento & purificação , Venenos de Anfíbios/farmacologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Medicina Tradicional/métodos , Venenos de Anfíbios/química , Animais , Bufo marinus , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Células Cultivadas , Feminino , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , ParaguaiRESUMO
BACKGROUND: Multichamber bags (MCBs) may offer potential clinical, ergonomic, and economic advantages compared with (hospital) pharmacy compounded bags (COBs) and multibottle systems (MBSs). METHODS: A systematic literature review was performed to identify and assess the available evidence regarding advantages of MCBs compared with COBs and MBSs. Medline, Embase, the Cochrane Databases, and EconLit were searched for articles reporting clinical, ergonomic, and economic outcomes for MCBs compared with COBs or MBSs. The search was limited to studies conducted in hospitalized patients >2 years of age that were published in English between January 1990 and November 2014. The Population Intervention Comparison Outcomes Study Design (PICOS) framework was used for the analysis. RESULTS: From 1307 unique citations, 74 potentially relevant publications were identified; review of references identified 2 additional publications. Among the 76 publications, 18 published studies met the inclusion criteria. Most were retrospective in design. Ten studies reported clinical outcomes, including 1 prospective randomized trial and multiple retrospective analyses that reported a lower risk of bloodstream infection for MCBs compared with other delivery systems. Sixteen studies reported ergonomic and/or economic outcomes; most reported a potential cost benefit for MCBs, with consistent reports of reduced time and labor compared with other systems. The largest cost benefit was observed in studies evaluating total hospitalization costs. CONCLUSIONS: The systematic literature review identified evidence of potential clinical, ergonomic, and economic benefits for MCBs compared with COBs and MBSs; however, methodological factors limited evidence quality. More prospective studies are required to corroborate existing evidence.
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Análise Custo-Benefício , Equipamentos e Provisões , Custos Hospitalares , Hospitais , Nutrição Parenteral/métodos , Serviço de Farmácia Hospitalar , Comércio , Equipamentos e Provisões/economia , Ergonomia , Humanos , Farmácias , Serviço de Farmácia Hospitalar/economiaRESUMO
Cancer, a disease that currently affects approximately 14 million people, is characterized by abnormal cell growth with altered replication capacity, which leads to the development of tumor masses without apoptotic control. Resistance to the drugs used in chemotherapy and their side effects stimulate scientific research seeking new therapies to combat this disease. Molecules from flora and fauna with cytotoxic activity against tumor cells have been studied for their potential to become a source of pharmaceutical agents. In this regard, snake venoms have a variety of proteins and peptides that have proven biotechnological potential. In several studies, antibacterial action and antitumor activity have been observed. One of the most widely studied venom components are phospholipases A2. Snake venom phospholipases A2 (svPLA2s) comprise a large class of molecules that catalyze the hydrolysis of the sn-2 position of phospholipids releasing fatty acids and lysophospholipids and are related to a broad spectrum of biotechnological activities. In addition to their specific cytotoxicity against some tumor cell lines, inhibitory activity of angiogenesis, adhesion and cell migration has been described. The antitumor activity of svPLA2s was observed both in vitro and in vivo, but little is known about the mechanism of action of these proteins in promoting this activity. In this review, the main structural and functional characteristics of svPLA2s are discussed, along with the mechanisms proposed, thus far, to explain their antitumor activity, targeting their potential use as a therapeutic alternative against cancer.
Assuntos
Antineoplásicos/farmacologia , Neoplasias/patologia , Peptídeos/farmacologia , Fosfolipases A2/metabolismo , Venenos de Serpentes/enzimologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Peptídeos/síntese químicaRESUMO
We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigotes. 9c showed excellent in vivo activity (up to 97% inhibition of the parasite growth) in a short-term treatment murine model for acute infection by L. infantum. In addition, the effect of compounds 9c and 14d on tubulin as potential target was assessed by confocal microscopy analysis applied to L. infantum promastigotes.
Assuntos
Benzeno/química , Benzeno/farmacologia , Desenho de Fármacos , Leishmania/efeitos dos fármacos , Sulfonamidas/química , Sulfonamidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/química , Antiprotozoários/farmacocinética , Antiprotozoários/farmacologia , Antiprotozoários/toxicidade , Benzeno/farmacocinética , Benzeno/toxicidade , Linhagem Celular , Simulação por Computador , Feminino , Humanos , Camundongos , Relação Estrutura-Atividade , Sulfonamidas/farmacocinética , Sulfonamidas/toxicidadeRESUMO
Introducción: el Tumor Triquilemal Proliferante es un tumor con diferenciación hacia estructuras pilosas, generalmente se presenta como un nódulo solitario en el cuero cabelludo en mujeres de edad avanzada. es considerado benigno pero con un comportamiento incierto dada su agresividad local y tendencia a la recidiva. Su característica histológica principal es la presencia de queratinización triquilemal. Objetivo: hacer una caracterización clínica e histopatológica de esta entidad. Presentación del caso: se presenta un caso de un Tumor Triquilemal Proliferante en el cuero cabelludo de una mujer de 66 años como un nódulo solitario. Se explican los resultados del estudio y la importancia de su diagnóstico preciso dada la posibilidad de su confusión con otras lesiones cutáneas como el quiste epidérmico. Conclusiones: el Tumor Triquilemal Proliferante es una entidad a tener en cuenta en el diagnóstico diferencial de lesiones tumorales en el cuero cabelludo con características distintivas específicas.
Introduction: proliferating trichilemmal tumor is tumor with follicular isthmus, that usually presents as a solitary nodule on the scalp of elderly women. It is considered a benign neoplasm but with an uncertain behavior because of its local aggressiveness and recidivant tendency. Its main histological characteristic is the presence of trichilemmal keratinization. Objective: to make a clinical and histopathological characterization of this condition. Case presentation: we describe a case of a Proliferating trichilemmal tumor on the scalp of a 66-year-old female, presenting as a solitary nodule. Results of the anatomo-pathological study are presented emphasizing in the importance of its precise diagnosis because the possibility of confusion with other cutaneous conditions like epidermal cyst. Conclusions: proliferating trichilemmal tumor is an entity to keep in mind in the differential diagnosis of tumoral lesions of the scalp with distinctive and specific characteristics.
RESUMO
An 80-year-old man was admitted to hospital with low-grade fever, weight loss, asthenia and anorexia. Physical examination revealed generalised ichthyosis with palmoplantar hyperkeratosis. CT scan showed retroperitoneal and inguinal lymph node enlargement. An inguinal lymph node biopsy revealed Hodgkin's disease (nodular-sclerosing subtype). The patient received chemotherapy, showing a clear improvement of both skin lesions and lymph nodes.
Assuntos
Doença de Hodgkin/diagnóstico , Ictiose/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Idoso de 80 Anos ou mais , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Ictiose/patologia , Linfonodos/patologia , Masculino , Síndromes Paraneoplásicas/patologiaRESUMO
End-stage renal disease (ESRD) is a major health problem in the world, including Cuba. There is an increasing trend in both the incidence and prevalence of ESRD. Global projections consistently show an increase of patients in maintenance dialysis, and also an epidemic trend in diabetes mellitus and hypertension, two diseases that are leading causes of ESRD in most countries. A new paradigm is necessary to handle this major health problem, such as a public health model that integrates health promotion and disease prevention. In 1996, the Ministry of Public Health of Cuba launched a national program for the prevention of chronic renal failure (CRF). The progressive implementation of this program follows several steps: the analysis of the resources and health situation in the country; epidemiological research to define the burden of CRF; continuing education for nephrologists, family doctors, and other health professionals; and reorientation of primary health care toward increased nephrology services, intervention, and surveillance. The main outcomes of the program have been: a rational redistribution of nephrology services in corresponding health areas of primary health care; nephrologists being brought closer to the community; an improvement in the knowledge and ability of family doctors and nephrologists in the prevention of chronic renal disease; an increase in the number of patients with CRF (serum creatinine > or = 133 micromol/L or > or = 1.5 mg/dL, or a glomerular filtration rate < 60 mL/min) who are registered in primary health care every year, from a prevalence of 0.59 per 1,000 inhabitants at the beginning of the program in 1996 to 0.92 per 1,000 inhabitants in 2002, with a mean prevalence growth of 9.2% per year; a significant reduction (0.1%) in the incidence of viral hepatitis B in dialysis patients after the implementation of vaccination against viral hepatitis B in CRF patients who are registered in primary health care; and the implementation of CRF surveillance in primary health care, which provides periodic information on CRF burden, patterns, and trends to assist evidence-based public-health decision making, and measures the impact of interventions in the population. Primary health care is an essential tool, and the community is an appropriate social space for health promotion and the prevention of CRF and ESRD.