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Introduction: The Mycobacterium chelonae species and the M. avium and M. abscessus complexes are emerging pathogens that cause mycobacteriosis. Treatment depends on the species and subspecies identified. The drugs of choice are macrolides and aminoglycosides. However, due to the resistance identified to these drugs, determining the microbe's sensitivity profile will allow clinicians to improve the understanding of the prognosis and evolution of these pathologies. Objective: To describe the macrolide and aminoglycoside susceptibility profile of cultures identified by Colombia's Laboratorio Nacional de Referencia de Mycobacteria from 2018 to 2022, as Mycobacterium avium complex, M. abscessus complex, and M. chelonae. Materials and methods. This descriptive study exposes the susceptibility profile to macrolides and aminoglycosides of cultures identified as M. avium complex, M. abscessus complex, and M. chelonae using the GenoType® NTM-DR method. Materials and methods: This descriptive study exposes the susceptibility profile to macrolides and aminoglycosides of cultures identified as M. avium complex, M. abscessus complex, and M. chelonae using the GenoType® NTM-DR method. Results: We identified 159 (47.3 %) cultures as M. avium complex, of which 154 (96.9 %) were sensitive to macrolides, and 5 (3.1 %) were resistant; all were sensitive to aminoglycosides. From the 125 (37.2 %) cultures identified as M. abscessus complex, 68 (54.4 %) were sensitive to macrolides, 57 (45.6 %) were resistant to aminoglycosides, and just one (0.8 %) showed resistance to aminoglycosides. The 52 cultures (15.5 %) identified as M. chelonae were sensitive to macrolides and aminoglycosides. Conclusions: The three studied species of mycobacteria have the least resistance to Amikacin. Subspecies identification and their susceptibility profiles allow the establishment of appropriate treatment schemes, especially against M. abscessus.
Introducción. Mycobacterium chelonae y los complejos Mycobacterium avium y M. abscessus, son agentes patógenos emergentes causantes de micobacteriosis. El tratamiento de esta infección depende de la especie y la subespecie identificadas. Los fármacos de elección son los macrólidos y aminoglucósidos, contra los cuales se ha reportado resistencia; por esta razón, el determinar el perfil de sensibilidad le permite al médico tratante comprender mejor el pronóstico y la evolución de estas infecciones. Objetivo. Describir los perfiles de sensibilidad ante macrólidos y aminoglucósidos, de los cultivos identificados como complejo Mycobacterium avium, complejo M. abscessus o especie M. chelonae, en el Laboratorio Nacional de Referencia de Micobacterias durante los años 2018 a 2022. Materiales y métodos. Se llevó a cabo un estudio descriptivo del perfil de sensibilidad a macrólidos y aminoglucósidos, de los cultivos identificados como complejo M. avium, complejo M. abscessus o M. chelonae, mediante la metodología GenoType® NTM-DR. Resultados. Los cultivos del complejo M. avium fueron 159 (47,3 %), de los cuales, 154 (96,9 %) fueron sensibles y 5 (3,1 %) resistentes a los macrólidos; todos fueron sensibles a los aminoglucósidos. Del complejo M. abscessus se estudiaron 125 (37,2 %) cultivos, 68 (54,4 %) resultaron sensibles y 57 (45,6 %) resistentes a los macrólidos; solo un cultivo (0,8 %) fue resistente a los aminoglucósidos. De M. chelonae se analizaron 52 cultivos (15,5 %), todos sensibles a los macrólidos y aminoglucósidos. Conclusiones. En las tres especies de micobacterias estudiadas, la resistencia contra la amikacina fue la menos frecuente. La identificación de las subespecies y los perfiles de sensibilidad permiten instaurar esquemas de tratamiento adecuados, especialmente en las micobacteriosis causadas por M. abscessus.
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Aminoglicosídeos , Macrolídeos , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Complexo Mycobacterium avium , Mycobacterium chelonae , Macrolídeos/farmacologia , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/genética , Mycobacterium abscessus/isolamento & purificação , Colômbia/epidemiologia , Mycobacterium chelonae/efeitos dos fármacos , Mycobacterium chelonae/genética , Mycobacterium chelonae/isolamento & purificação , Aminoglicosídeos/farmacologia , Humanos , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Prevalência , Farmacorresistência Bacteriana MúltiplaRESUMO
OBJECTIVE: To describe the reported cases of newborns subjected to tuberculosis preventive treatment (TPT) in the state of Paraná, Brazil, and to evaluate the safety and effectiveness in preventing the progression of TB disease in this population. METHOD: Observational, descriptive case series, with secondary data. The characteristics of the participants were analyzed from the information systems of preventive treatment of TB (of Paraná), between 2009 and 2016. To evaluate which children had developed tuberculosis later or died, we used the data from the information systems of TB (in Brazil), and mortality (in Paraná), covering the years 2009 to 2018. RESULTS: A total of 24 children underwent TPT with the age at treatment onset ranging from 0 to 87 days (median: 23 days). In 95.8 %, the exposure occurred at home, and in 33.3 % of cases, the mother was the source of the infection. A total of 20.8 % of the children tested positive for tuberculosis test at 3 months of age, 83.3 % completed treatment, and 2 experienced adverse events (gastrointestinal issues). No children developed TB or died during the minimum of a 2-year evaluation period through the official databases. CONCLUSIONS: In this case series, the adherence to the plan was high, with few adverse events and 100 % protection against infection.
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The latent potential of active ingredients derived from agro-industrial waste remains largely untapped and offers a wealth of unexplored resources. While these types of materials have applications in various fields, their ability to benefit human health needs to be further explored and investigated. This systematic review was conducted to systematically evaluate non-clinical studies that have investigated the biological effects of fractions, extracts and bioactive compounds from agro-industrial wastes and their potential therapeutic applications. Articles were selected via PubMed, Embase and Medline using the descriptors (by-products[title/abstract]) AND (agro-industrial[title/abstract]). The systematic review was registered in the International Prospective Register of Systematic Reviews (Prospero) under the number CRD42024491021. After a detailed analysis based on inclusion and exclusion criteria, a total of 38 articles were used for data extraction and discussion of the results. Information was found from in vitro and in vivo experiments investigating a variety of residues from the agro-industry. The studies investigated peels, pomace/bagasse, pulp, seeds, aerial parts, cereals/grains and other types of waste. The most studied activities include mainly antioxidant and anti-inflammatory effects, but other activities such as antimicrobial, cytotoxic, antiproliferative, antinociceptive, hypoglycemic, antihyperglycemic and anticoagulant effects have also been described. Finally, the studies included in this review demonstrate the potential of agro-industrial waste and can drive future research with a focus on clinical application.
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Agricultura , Resíduos Industriais , Animais , Humanos , Agricultura/métodos , AntioxidantesRESUMO
OBJECTIVE: To describe the findings of children with Robin Sequence (RS) who received sensory-motor-oral stimulation combined with early sucking during mandibular distraction osteogenesis (MDO), compared with children who did not receive the intervention. DESIGN: A quasi-experimental study. Setting: A tertiary public hospital. Patients: Children with RS referred to MDO. A historical group from the same population but managed according to the institution's standard protocol (no sucking) served as a control group. Interventions: Sensory-motor-oral stimulation, including sucking, starting 24â h after MDO (intervention group). Main Outcome Measure: Our hypothesis is that sensory-motor-oral stimulation, including sucking during the DOM process, do not negatively affect surgical outcomes. RESULTS: Twenty-nine children were included. Eight (72.7%) of the 11 patients in the intervention group and 13 (72.2%) of the 18 controls had MDO complications, with no significant difference between the groups (p = 1.000). The most common surgical outcome was antibiotic therapy for surgical site infection (76.2%). Six months after MDO, 22 (75.9%) children attained full oral feeding or associated with alternative feeding methods. CONCLUSION: The intervention group did not have higher complication rates, from a surgical point of view, than control group. The protocol adopted by some centers that contraindicates sucking during MDO should be revised to consider the benefits of such stimulation. Keywords: Pierre Robin Syndrome, deglutition, therapeutics, child development.
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BACKGROUND: Colombian indigenous Wiwas are exposed to a variety of partly complex medical conditions with a predominance of infectious diseases. The study provided here aims at verifying of falsifying previous suspicions on therapeutic shortcomings and neglect of disease categories. MATERIAL AND METHODS: Local diagnoses within various subpopulations of indigenous Wiwas obtained by a study physician and local health brigades and health points between 2017 and 2018 were coded following the ICD 10 classification from 2019. Proportions of diagnoses per ICD-10 sub-chapter were evaluated to find diseases and to rank the occurrence of diagnoses in the population of indigenous people. Thereafter, the available medication provided by the indigenous health care provider Dusakawi for the treatment of the indigenous patients was analyzed in regard of its sufficiency to cover the recorded diseases. RESULTS: The majority of the diseases found in the communities cannot at all (32%) or only partially (56%) be treated according to available guidelines. Only few (12%), predominantly infectious diseases, were covered completely by the provided medication. Notably, there are some ICD chapters with diseases that do only rarely appear at all in the gained datasets, e.g., complications during birth, mental disorders or cancer. CONCLUSIONS: An expansion and revision of the medical supply for the indigenous population of the Sierra Nevada de Santa Marta is needed. An emergency kit for medical brigades and health points should be provided and in place. Awareness for neglected diseases needs to be created.
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INTRODUCTION AND OBJECTIVES: The absence of melanoma 2 (AIM2) protein triggers the activation of the inflammasome cascade. It is unclear whether AIM2 plays a role in hepatocellular carcinoma (HCC) and radiofrequency ablation (RFA), which uses radiofrequency waves to treat tumors. In this study, we investigated if RFA could induce pyroptosis, also called cell inflammatory necrosis, in HCC through AIM2-inflammasome signaling in vivo and in vitro. MATERIALS AND METHODS: BALB/c nude mice were used to generate HepG2 or SMMC-7721 cell-derived tumor xenografts. HCC cells with knockdown or overexpression of AIM2 were created using short hairpin RNA (shRNA) and expression vector transfection, respectively, for functional and mechanistic studies. Downstream effects were examined using flow cytometry, qRT-PCR, ELISAs, and other molecular assays. RESULTS: RFA significantly suppressed tumor growth in HCC cell xenografts. Flow cytometry analysis revealed that RFA could induce pyroptosis. Furthermore, AIM2, NLRP3, caspase-1, γ-H2AX, and DNA-PKc had significantly greater expression levels in liver tissues from mice treated with RFA compared with those of the controls. Additionally, interleukin (IL)-1ß and IL-18 expression levels were significantly higher in the HCC cell-derived xenograft mice treated with RFA compared with those without RFA. Notably, a significantly greater effect was achieved in the RFA complete ablation group versus the partial ablation group. Knockdown or overexpression of AIM2 in HCC cells demonstrated that AIM2 exerted a role in RFA-induced pyroptosis. CONCLUSIONS: RFA can suppress HCC tumor growth by inducing pyroptosis via AIM2. Therefore, therapeutically intervening with AIM2-mediated inflammasome signaling may help improve RFA treatment outcomes for HCC patients.
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Monotherapy is the recommended initial treatment for early Parkinson's disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson's disease.
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Antiparkinsonianos , Agonistas de Dopamina , Levodopa , Doença de Parkinson , Humanos , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/farmacologia , Antiparkinsonianos/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/administração & dosagem , Índice de Gravidade de DoençaRESUMO
The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.
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Advances in molecular biology achieved during the last years have allowed us to know the genes involved in biliary secretion and the mutations capable of generating cholestasis. The mechanisms involved in forming bile and its circulation have been clarified. According to the biology of biliary secretion, we classify the genetic causes of cholestasis as follows: 1) transport abnormalities in canalicular or basolateral membranes, 2) alterations in intracellular vesicle transit, 3) increased paracellular permeability, 4) mutations in nuclear receptors, 5) cholangiopathies, and 6) hepatocellular diseases, due to disturbance of the function of intracellular organelles or errors of metabolism. This physiopathological classification of chronic cholestasis in childhood will facilitate pediatricians' diagnostic guidance and timely specialized referrals, as patients should receive early and appropriate treatment for its complications.
Los avances en biología molecular alcanzados durante los últimos años nos han permitido conocer los genes que intervienen en la secreción biliar y las mutaciones capaces de generar un cuadro de colestasis. Los mecanismos involucrados en la formación de la bilis y su circulación han sido precisados. De acuerdo a la biología de la secreción biliar, clasificamos las causas genéticas de colestasis en 1) anomalías del transporte en las membranas canalicular o basolateral, 2) alteraciones del tránsito de vesículas intracelulares, 3) aumento de la permeabilidad paracelular, 4) mutaciones en los receptores nucleares, 5) colangiopatías, 6) enfermedades hepatocelulares, por perturbación de la función de orgánulos intracelulares o errores del metabolismo. Esta clasificación fisiopatológica de las colestasis crónicas de la infancia facilitará la orientación diagnóstica de los pediatras y la derivación especializada oportuna, ya que los pacientes deben recibir tempranamente un tratamiento adecuado a las complicaciones de la colestasis.
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Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It's crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components.
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Inseticidas , Poliaminas , Venenos de Aranha , Vespas , Animais , Poliaminas/química , Venenos de Aranha/química , Venenos de Aranha/toxicidade , Inseticidas/farmacologia , Inseticidas/química , Inseticidas/toxicidade , Humanos , AranhasRESUMO
ABSTRACT Monotherapy is the recommended initial treatment for early Parkinson´s disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson´s disease.
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El objetivo de este estudio fue describir las alternativas terapéuticas ortodóncico-quirúrgicas más utilizadas en la actualidad para el manejo de la displasia cleidocraneal en pacientes en crecimiento. Se realizó una búsqueda de literatura durante mayo de 2023 en las bases de datos Pubmed, Epitemonikos, Dentistry & Oral Sciences Source y LILACS sobre reporte de casos que presentaran estrategias de tratamiento ortodóncico-quirúrgico en pacientes menores de 18 años con displasia cleidocraneal. Seis artículos cumplieron con los criterios de inclusión. De ellos se obtuvieron siete reportes de casos. Las edades de los pacientes fluctúan entre los 10 y 16 años. Las estrategias de tratamiento consisten en al menos dos etapas de tratamiento ortodóncico quirúrgicas que involucran la extracción de dientes primarios y supernumerarios y la exposición quirúrgica de dientes permanentes retenidos para permitir su erupción y/o su tracción ortodóncica. Algunos casos son finalizados con cirugía Ortognática (Osteotomía Le Fort I de avance maxilar). La extracción de dientes primarios y supernumerarios, fenestración y tracción ortodóncica de los dientes permanentes retenidos y la cirugía ortognática al finalizar el crecimiento (cuando sea necesario) se propone actualmente como la mejor alternativa terapéutica para el tratamiento de pacientes con displasia cleidocraneal.
The objective of this study was to describe the orthodontic-surgical therapeutic alternatives most used nowadays, for the management of CCD in growing patients. A literature search for case reports was carried out through May, 2023 in PubMed, Epitemonikos, Dentistry & Oral Sciences Source and LILACS databases. We included case reports that presented complete orthodontic-surgical treatment strategies in patients with DCC under 18 years of age. Six articles met the inclusion criteria and seven case reports were identified. The age of cases ranged from 10 to 16 years. Treatment strategies consisted of at least two stages of surgical orthodontic treatment involving extraction of primary and supernumerary teeth and surgical exposure of impacted permanent teeth to allow spontaneous eruption or orthodontic traction. Some cases were completed with orthognathic surgery. Extraction of primary and supernumerary teeth, fenestration and orthodontic traction of retained permanent teeth and orthognathic surgery at the end of growth (when necessary) is currently proposed as the best therapeutic alternative for the treatment of patients with DCC.
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Resumen El carcinoma sarcomatoide primario hepático es un tumor agresivo que representa el 0.4-0.7% de todas las neoplasias primarias hepáticas. Se asocia a hepa topatía por virus hepatotropos, es más prevalente en la población asiática y en su histología se evidencian componentes de carcinoma y sarcoma. No posee carac terísticas clínicas ni imagenológicas patognomónicas y su diagnóstico se realiza en base a los hallazgos de la anatomía patológica e inmunohistoquímica. La cirugía en estadio localizado representa la única modalidad terapéutica con impacto en la sobrevida. Reportamos el caso de una paciente de 72 años, coreana, con an tecedentes de hepatopatía crónica por virus B, a quien se le diagnosticó un carcinoma sarcomatoide hepático primario con metástasis ósea y ganglionares.
Abstract Primary hepatic sarcomatoid carcinoma is a very ag gressive tumor, representing 0.4-0.7% of all primary he patic neoplasms. The disease is associated with liver dis ease due to hepatotropic viruses and is more prevalent in Asians. Histology shows sarcomatous and carcinoma components. It does not have pathognomonic clinical or imaging characteristics and its diagnosis is based on the pathological and immunohistochemistry findings. Surgery could prolong survival in localized stages. We report the case of a 72-year-old Korean patient with a history of chronic liver disease due to B virus, who was diagnosed with primary hepatic sarcomatoid carcinoma with bone and lymph node metastases.
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BACKGROUND: Low targeting efficacy and high toxicity continue to be challenges in Oncology. A promising strategy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. RESULTS: Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identified 6-O-α-rhamnosyl-ß-glucosidase (αRßG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRßG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resorcinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without significant affecting normal pancreatic epithelial cells. PR exhibited the highest efficacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates significantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. CONCLUSIONS: αRßG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suitable option to enhance the anti-proliferative effect of bioactive compounds. This finding opens up new possibilities for developing more effective therapies for pancreatic cancer and other solid malignancies.
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Antineoplásicos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Hypocreales/metabolismo , Rutina/farmacologia , Rutina/química , Acremonium , Gencitabina , Dissacarídeos/farmacologia , Dissacarídeos/químicaRESUMO
MicroRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in regulating gene expression at the post-transcriptional level. These regulatory molecules are integral to many biological processes and have been implicated in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV) infection. This review aims to cover the current understanding of the multifaceted roles miRNAs assume in the context of HIV infection and pathogenesis. The discourse is structured around three primary focal points: (i) elucidation of the mechanisms through which miRNAs regulate HIV replication, encompassing both direct targeting of viral transcripts and indirect modulation of host factors critical for viral replication; (ii) examination of the modulation of miRNA expression by HIV, mediated through either viral proteins or the activation of cellular pathways consequent to viral infection; and (iii) assessment of the impact of miRNAs on the immune response and the progression of disease in HIV-infected individuals. Further, this review delves into the potential utility of miRNAs as biomarkers and therapeutic agents in HIV infection, underscoring the challenges and prospects inherent to this line of inquiry. The synthesis of current evidence positions miRNAs as significant modulators of the host-virus interplay, offering promising avenues for enhancing the diagnosis, treatment, and prevention of HIV infection.
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Infecções por HIV , MicroRNAs , Replicação Viral , Humanos , MicroRNAs/genética , Infecções por HIV/genética , Infecções por HIV/virologia , Replicação Viral/genética , HIV-1/genética , Interações Hospedeiro-Patógeno/genética , Biomarcadores , Regulação da Expressão GênicaRESUMO
Objective This study evaluated the epidemiological data and functional outcomes from patients with concomitant distal radial and scaphoid fractures treated in a single center specialized in hand surgery. Functional outcomes analysis used validated instruments. Methods Patients diagnosed with distal radial and scaphoid fractures treated from January 2011 to December 2021 underwent assessments using the Disabilities of the Arm, Shoulder and Hand (DASH), Patient-Rated Wrist Evaluation (PRWE), Visual Analog Scale (VAS) for pain, goniometry, radiographic consolidation, and complications six months after surgery. Results The study included 23 patients, 73.9% men and 26.1% women. Most (56.5%) fractures occurred on the right side, and 43.5% happened on the left side. Treatment of most (56%) distal radial fractures used a locked volar plate. Functional assessment by PRWE resulted in a mean score of 35.9 points (range, 14 to 71 points), while DASH showed a mean score of 37.8 points (range, 12 to 78 points). The mean VAS was 2.33 during activities (range, 0.6 to 6.2). Conclusion Distal radial fractures associated with scaphoid fractures resulted from high-energy trauma, and most patients were males. There was a low rate of complications with surgical treatment, and the patients had satisfactory functional evolution with a low level of pain.
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The objective of this work was to evaluate the combination of synthetic peptides based on the γ-core motif of defensin PvD1 with amphotericin B (AmB) at different concentrations against Candida albicans. We applied the checkerboard assay using different concentrations of the commercial drug AmB and the synthetic peptides γ31-45PvD1++ and γ33-41PvD1++ against C. albicans, aiming to find combinations with synergistic interactions. Between these two interactions involving γ31-45PvD1++ and AmB, an additive effect was observed. One such interaction occurred at concentrations of 0.009 µM of peptide γ31-45PvD1++ and 13.23 µM of AmB and another condition of 0.019 µM of peptide γ31-45PvD1++ and 6.61 µM of AmB. The other two concentrations of the interaction showed a synergistic effect in the combination of synthetic peptide γ31-45PvD1++ and AmB, where the concentrations were 1.40 µM peptide γ31-45PvD1++ and 0.004 µM AmB and 0.70 µM γ31-45PvD1++ peptide and 0.002 µM AmB. We proceeded with analysis of the mechanism of action involving synergistic effects. This examination unveiled a range of impactful outcomes, including the impairment of mitochondrial functionality, compromise of cell wall integrity, DNA degradation, and a consequential decline in cell viability. We also observed that both synergistic combinations were capable of causing damage to the plasma membrane and cell wall, causing leakage of intracellular components. This discovery demonstrates for the first time that the synergistic combinations found between the synthetic peptide γ31-45PvD1++ and AmB have an antifungal effect against C. albicans, acting on the integrity of the plasma membrane and cell wall.
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Anfotericina B , Candida albicans , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Peptídeos/farmacologia , Membrana Celular , Parede Celular , Testes de Sensibilidade MicrobianaRESUMO
Introduction: Management of pediatric cancer patients involves invasive procedures such as punctures, injections, catheter placements, and chemotherapy which can generate fatigue, nausea, vomiting, anxiety, and pain. Virtual Reality (VR) is a nonpharmacological intervention classified as a cognitive-behavioral method to relieve symptoms. Methods: We designed a crossover protocol and included 20 patients between 9 and 12 years old; ten were male. All patients had acute lymphoblastic leukemia diagnosis and were treatedwith St. Jude's XV protocol in the maintenance phase. Pain and anxiety were measured with validated scales in the pediatric population. Results: Although we used a small group of patients, we found statistical difference in the reduction of anxiety and perception of time. Discussion: These results open a window to non-pharmacological treatments and show a strategy to improve quality of life in children inside the hospital.