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Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

Asunto(s)

Própolis , Humanos , Própolis/farmacología , Simulación del Acoplamiento Molecular , Flavonoides/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Brasil

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OBJECTIVES: Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. METHODS: Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. RESULTS: MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p < 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1ß and Nuclear Transcription Factor-κB (NF-κB) (p < 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p < 0.05). CONCLUSION: NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Exosomas , MicroARNs , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Exosomas/genética , Exosomas/metabolismo , Exosomas/patología , Infecciones por Virus de Epstein-Barr/genética , Línea Celular Tumoral , Proliferación Celular , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Regulación Neoplásica de la Expresión Génica , Proteínas que Contienen Bromodominio , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo

RESUMEN

Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.

RESUMEN

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease closely linked to cardiovascular disease (CVD). This study aims to investigate the connection between early-stage NAFLD and atherosclerosis, as well as the correlation between liver fibrosis and coronary heart disease while exploring underlying inflammatory mechanisms. METHODS: In this retrospective study, the authors analyzed data from 607 patients who underwent both coronary computed tomography angiography (CCTA) and abdominal ultrasonography (US). Logistic regression was utilized to examine the association between NAFLD and atherosclerosis, while mediation analysis was conducted to explore whether inflammatory markers mediate the link between liver fibrosis and coronary artery disease. RESULTS: Among the 607 patients included, 237 (39.0 %) were diagnosed with NAFLD through ultrasonography. After adjusting for traditional cardiovascular risk factors, ALT, and AST, NAFLD demonstrated a significant correlation with carotid intimal thickening (1.58, 95 % CI 1.04‒2.40; p = 0.034) and non-calcified plaque (1.56, 95 % CI 1.03‒2.37; p = 0.038). Additionally, fibrosis predictive markers, including FIB-4 > 1.3 (1.06, 95 % CI 2.30‒5.00; p = 0.035) and APRI (6.26, 95 % CI 1.03‒37.05; p = 0.046), independently correlated with coronary heart disease after adjusting for cardiovascular risk factors. Conversely, among systemic inflammatory markers, only the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) are independently associated with coronary heart disease. ROC curve analysis indicated that combining predictive fibrosis markers or inflammatory markers with traditional cardiovascular risk factors enhanced the predictive accuracy for coronary heart disease. Mediation analysis revealed that NLR fully mediated the effect of liver fibrosis on coronary heart disease. CONCLUSION: NAFLD is associated with carotid intimal thickening and non-calcified plaque, suggesting an increased cardiovascular risk. Furthermore, liver fibrosis independently increases the risk of coronary heart disease in the early-stage NAFLD population, and inflammation may play a fully mediating role in the effect of liver fibrosis on coronary heart disease. Early intervention is crucial for NAFLD patients to mitigate future major adverse cardiovascular events.

Asunto(s)

Aterosclerosis , Enfermedad de la Arteria Coronaria , Enfermedad del Hígado Graso no Alcohólico , Placa Aterosclerótica , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios Retrospectivos , Aterosclerosis/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Cirrosis Hepática , Inflamación/complicaciones

RESUMEN

The neglected tropical disease schistosomiasis impacts over 700 million people globally. Schistosoma mansoni, the trematode parasite that causes the most common type of schistosomiasis, requires planorbid pond snails of the genus Biomphalaria to support its larval development and transformation to the cercarial form that can infect humans. A greater understanding of neural signaling systems that are specific to the Biomphalaria intermediate host could lead to novel strategies for parasite or snail control. This study examined a Biomphalaria glabrata neural channel that is gated by the neuropeptide FMRF-NH2. The Biomphalaria glabrata FMRF-NH2 gated sodium channel (Bgl-FaNaC) amino acid sequence was highly conserved with FaNaCs found in related gastropods, especially the planorbid Planorbella trivolvis (91% sequence identity). In common with the P. trivolvis FaNaC, the B. glabrata channel exhibited a low affinity (EC50: 3 x 10-4 M) and high specificity for the FMRF-NH2 agonist. Its expression in the central nervous system, detected with immunohistochemistry and in situ hybridization, was widespread, with the protein localized mainly to neuronal fibers and the mRNA confined to cell bodies. Colocalization of the Bgl-FaNaC message with its FMRF-NH2 agonist precursor occurred in some neurons associated with male mating behavior. At the mRNA level, Bgl-FaNaC expression was decreased at 20 and 35 days post infection (dpi) by S. mansoni. Increased expression of the transcript encoding the FMRF-NH2 agonist at 35 dpi was proposed to reflect a compensatory response to decreased receptor levels. Altered FMRF-NH2 signaling could be vital for parasite proliferation in its intermediate host and may therefore present innovative opportunities for snail control.

Asunto(s)

Biomphalaria , Esquistosomiasis mansoni , Esquistosomiasis , Trematodos , Animales , Masculino , Humanos , Schistosoma mansoni/fisiología , Biomphalaria/parasitología , FMRFamida , Esquistosomiasis/parasitología , Sistema Nervioso Central , Esquistosomiasis mansoni/parasitología , Interacciones Huésped-Parásitos/fisiología

RESUMEN

Abstract Background and aims Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease closely linked to cardiovascular disease (CVD). This study aims to investigate the connection between early-stage NAFLD and atherosclerosis, as well as the correlation between liver fibrosis and coronary heart disease while exploring underlying inflammatory mechanisms. Methods In this retrospective study, the authors analyzed data from 607 patients who underwent both coronary computed tomography angiography (CCTA) and abdominal ultrasonography (US). Logistic regression was utilized to examine the association between NAFLD and atherosclerosis, while mediation analysis was conducted to explore whether inflammatory markers mediate the link between liver fibrosis and coronary artery disease. Results Among the 607 patients included, 237 (39.0 %) were diagnosed with NAFLD through ultrasonography. After adjusting for traditional cardiovascular risk factors, ALT, and AST, NAFLD demonstrated a significant correlation with carotid intimal thickening (1.58, 95 % CI 1.04‒2.40; p= 0.034) and non-calcified plaque (1.56, 95 % CI 1.03‒2.37; p= 0.038). Additionally, fibrosis predictive markers, including FIB-4 > 1.3 (1.06, 95 % CI 2.30‒5.00; p= 0.035) and APRI (6.26, 95 % CI 1.03‒37.05; p= 0.046), independently correlated with coronary heart disease after adjusting for cardiovascular risk factors. Conversely, among systemic inflammatory markers, only the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) are independently associated with coronary heart disease. ROC curve analysis indicated that combining predictive fibrosis markers or inflammatory markers with traditional cardiovascular risk factors enhanced the predictive accuracy for coronary heart disease. Mediation analysis revealed that NLR fully mediated the effect of liver fibrosis on coronary heart disease. Conclusion NAFLD is associated with carotid intimal thickening and non-calcified plaque, suggesting an increased cardiovascular risk. Furthermore, liver fibrosis independently increases the risk of coronary heart disease in the early-stage NAFLD population, and inflammation may play a fully mediating role in the effect of liver fibrosis on coronary heart disease. Early intervention is crucial for NAFLD patients to mitigate future major adverse cardiovascular events.

RESUMEN

Freshwater snails of the genus Biomphalaria serve as intermediate hosts for the digenetic trematode Schistosoma mansoni, the etiological agent for the most widespread form of intestinal schistosomiasis. As neuropeptide signaling in host snails can be altered by trematode infection, a neural transcriptomics approach was undertaken to identify peptide precursors in Biomphalaria glabrata, the major intermediate host for S. mansoni in the Western Hemisphere. Three transcripts that encode peptides belonging to the FMRF-NH2 -related peptide (FaRP) family were identified in B. glabrata. One transcript encoded a precursor polypeptide (Bgl-FaRP1; 292 amino acids) that included eight copies of the tetrapeptide FMRF-NH2 and single copies of FIRF-NH2 , FLRF-NH2 , and pQFYRI-NH2 . The second transcript encoded a precursor (Bgl-FaRP2; 347 amino acids) that comprised 14 copies of the heptapeptide GDPFLRF-NH2 and 1 copy of SKPYMRF-NH2 . The precursor encoded by the third transcript (Bgl-FaRP3; 287 amino acids) recapitulated Bgl-FaRP2 but lacked the full SKPYMRF-NH2 peptide. The three precursors shared a common signal peptide, suggesting a genomic organization described previously in gastropods. Immunohistochemical studies were performed on the nervous systems of B. glabrata and B. alexandrina, a major intermediate host for S. mansoni in Egypt. FMRF-NH2 -like immunoreactive (FMRF-NH2 -li) neurons were located in regions of the central nervous system associated with reproduction, feeding, and cardiorespiration. Antisera raised against non-FMRF-NH2 peptides present in the tetrapeptide and heptapeptide precursors labeled independent subsets of the FMRF-NH2 -li neurons. This study supports the participation of FMRF-NH2 -related neuropeptides in the regulation of vital physiological and behavioral systems that are altered by parasitism in Biomphalaria.

Asunto(s)

FMRFamida/genética , Neuropéptidos/genética , Esquistosomiasis mansoni/genética , Transcriptoma/genética , Secuencia de Aminoácidos , Animales , Biomphalaria , FMRFamida/análisis , FMRFamida/metabolismo , Neuropéptidos/análisis , Neuropéptidos/metabolismo , Imagen Óptica/métodos , Schistosoma mansoni/genética , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/metabolismo

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BACKGROUND: The damage inflicted by the coronavirus diseases 2019 (COVID-19) pandemic upon humanity is and will continue to be considerable. Unprecedented progress made in global health over the past 20 years has reverted and economic growth has already evaporated, giving rise to a global recession, the likes of which we may not have experienced since the Second World War. Our aim is to draw the attention of the neglected tropical disease (NTD) community towards some of the major emerging economic opportunities which are quickly appearing on the horizon as a result of COVID-19. MAIN TEXT: This scoping review relied on a literature search comprised of a sample of articles, statements, and press releases on initiatives aimed at mitigating the impact of COVID-19, while supporting economic recovery. Of note, the donor scenario and economic development agendas are highly dynamic and expected to change rapidly as the COVID-19 pandemic unfolds, as are donor and lender priorities. CONCLUSIONS: The NTD community, particularly in low- and middle-income countries (LMICs), will need to work quickly, diligently, and in close collaboration with decision-makers and key stakeholders, across sectors at national and international level to secure its position. Doing so might enhance the odds of grasping potential opportunities to access some of the massive resources that are now available in the form of contributions from corporate foundations, trust funds, loans, debt relieve schemes, and other financial mechanisms, as part of the ongoing and future economic development agendas and public health priorities driven by the COVID-19 pandemic. This paper should serve as a starting point for the NTD community to seek much needed financial support in order to sustain and revitalize control and elimination efforts pertaining to NTDs in LMICs.

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COVID-19/economía , COVID-19/epidemiología , Enfermedades Desatendidas/economía , Enfermedades Desatendidas/epidemiología , Estatus Económico , Salud Global , Humanos , Pandemias , Pobreza , Salud Pública , Factores de Riesgo , SARS-CoV-2 , Clima Tropical , Naciones Unidas , Organización Mundial de la Salud

RESUMEN

Emerging and re-emerging zoonotic diseases represent a public health challenge of international concern. They include a large group of neglected tropical diseases (NTDs), many of which are of zoonotic nature. Coronavirus disease 2019 (COVID-19), another emerging zoonotic disease, has just increased the stakes exponentially. Most NTDs are subject to the impact of some of the very same human-related activities triggering other emerging and re-emerging diseases, including COVID-19, severe acute respiratory syndrome (SARS), bird flu and swine flu. It is conceivable that COVID-19 will exacerbate the NTDs, as it will divert much needed financial and human resources. There is considerable concern that recent progress achieved with control and elimination efforts will be reverted. Future potential strategies will need to reconsider the determinants of health in NTDs in order to galvanize efforts and come up with a comprehensive, well defined programme that will set the stage for an effective multi-sectorial approach. In this Commentary, we propose areas of potential synergies between the COVID-19 pandemic control efforts, other health and non-health sector initiatives and NTD control and elimination programmes.

Asunto(s)

Enfermedades Transmisibles Emergentes/prevención & control , Infecciones por Coronavirus/epidemiología , Enfermedades Desatendidas/prevención & control , Neumonía Viral/epidemiología , Medicina Tropical/métodos , Animales , Betacoronavirus , COVID-19 , Enfermedades Transmisibles Emergentes/epidemiología , Infecciones por Coronavirus/prevención & control , Salud Global , Humanos , Colaboración Intersectorial , Enfermedades Desatendidas/epidemiología , Pandemias/prevención & control , Neumonía Viral/prevención & control , Asignación de Recursos , SARS-CoV-2 , Medicina Tropical/tendencias , Zoonosis/epidemiología , Zoonosis/prevención & control

RESUMEN

BACKGROUND: Due to the relative short life span and the limited spatial movement, porcine cysticercosis is an excellent indicator of current local active transmission. The aim of this study was to map at province-level, the occurrence of T. solium and T. asiatica in pigs and areas at risk of transmission to pigs in East and Southeast Asia, based on the density of extensive pig production systems and confirmed reports of porcine cysticercosis. METHODS: This study covered East and Southeast Asia, which consist of the following countries: Brunei, Cambodia, China, East Timor, Indonesia, Japan, Laos, Malaysia, Mongolia, Myanmar, North Korea, Philippines, Singapore, South Korea, Thailand and Vietnam. Literature searches were carried out to identify current epidemiological data on the occurrence of porcine cysticercosis caused by T. solium and T. asiatica infections. Modelled densities of pigs in extensive production systems were mapped and compared to available data on porcine cysticercosis. RESULTS: Porcine cysticercosis was confirmed to be present during the period 2000 to 2018 in eight out of the 16 countries included in this study. Taenia solium porcine cysticercosis was confirmed from all eight countries, whereas only one country (Laos) could confirm the presence of T. asiatica porcine cysticercosis. Province-level occurrence was identified in five countries (Cambodia, Indonesia, Laos, Myanmar, and Vietnam) across 19 provinces. Smallholder pig keeping is believed to be widely distributed throughout the region, with greater densities predicted to occur in areas of China, Myanmar, Philippines and Vietnam. CONCLUSIONS: The discrepancies between countries reporting taeniosis and the occurrence of porcine cysticercosis, both for T. solium and T. asiatica, suggests that both parasites are underreported. More epidemiological surveys are needed to determine the societal burden of both parasites. This study highlights a straightforward approach to determine areas at risk of porcine cysticercosis in the absence of prevalence data.

Asunto(s)

Cisticercosis/parasitología , Cisticercosis/veterinaria , Enfermedades de los Porcinos/parasitología , Taenia solium/aislamiento & purificación , Taenia/aislamiento & purificación , Animales , Asia Sudoriental/epidemiología , Cisticercosis/epidemiología , Asia Oriental/epidemiología , Humanos , Porcinos , Enfermedades de los Porcinos/epidemiología , Taenia/clasificación , Taenia/genética , Taenia solium/clasificación , Taenia solium/genética

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Disfunção de prótese valvar cardíaca (PVC) é rara, porém é uma potencial ameaça à vida. Estabelecer o exato mecanismo da disfunção da PVC é desafiador, no entanto é essencial para determinar a estratégia terapêutica apropriada. Na prática clinica, uma abordagem abrangente que integra vários parâmetros de morfologia e função avaliados pelo eco transtorácico 2D/3D e transesofágico são fundamentais para detectar e quantificar a disfunção da PVC. A cinefluoroscopia, a tomografia computadorizada com multidectetores, a ressonância magnética cardíaca, e em menor escala, a imagem nuclear, são ferramentas complementares para o diagnóstico e abordagem das complicações das PVC. Este documento apresenta recomendações para o uso de imagem em multimodalidade para avaliação das PVCs

Asunto(s)

Humanos , Masculino , Femenino , Diagnóstico por Imagen , Ecocardiografía Transesofágica/métodos , Ecocardiografía/métodos , Prótesis Valvulares Cardíacas/normas , Espectroscopía de Resonancia Magnética/métodos , Tomografía Computarizada Multidetector/métodos , Válvula Aórtica , Bioprótesis , Diagnóstico Diferencial , Ecocardiografía Doppler/métodos , Ecocardiografía de Estrés/métodos , Hemodinámica , Válvula Mitral , Medicina Nuclear/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prótesis e Implantes , Estudios de Evaluación como Asunto , Estudios de Evaluación como Asunto , Stents , Volumen Sistólico , Trombosis , Tomografía Computarizada por Rayos X/métodos , Válvula Tricúspide

RESUMEN

ABSTRACT Introduction To evaluate the safety and efficacy of a novel penile circumcision suturing devices PCSD and Shang ring (SR) for circumcision in an adult population. Materials and Methods A total of 124 outpatients were randomly assigned to receive PCSD (n=62) or SR (n=62). Patient characteristics, operative time, blood loss, return to normal activities time (RNAT), visual analogue scale (VAS), scar width, wound healing time, cosmetic result, and complications were recorded. Results There were no significant differences in blood loss, RNAT, or complications between the two groups. There were no significant differences in the VAS scores at the operation, at 6 or 24 hours after surgery (P>0.05). The wound scar width was wider in the SR group than in the PCSD group (P<0.01). Patients in the SR group had significantly longer wound healing time compared with those in the PCSD group (P<0.01). Patients who underwent PCSD were significantly more satisfied with the cosmetic results (P<0.01). Conclusions SR and PCSD are safe and effective minimally invasive techniques for adult male circumcision. Compared with SRs, PCSDs have the advantages of faster postoperative incision healing and a good effect on wound cosmetics.

Asunto(s)

Humanos , Masculino , Adolescente , Adulto , Anciano , Adulto Joven , Fimosis/cirugía , Técnicas de Sutura/instrumentación , Circuncisión Masculina/instrumentación , Dolor Postoperatorio , Suturas , Estudios Prospectivos , Circuncisión Masculina/métodos , Resultado del Tratamiento , Tempo Operativo , Persona de Mediana Edad

RESUMEN

INTRODUCTION: To evaluate the safety and efficacy of a novel penile circumcision suturing devices PCSD and Shang ring (SR) for circumcision in an adult population. MATERIALS AND METHODS: A total of 124 outpatients were randomly assigned to receive PCSD (n=62) or SR (n=62). Patient characteristics, operative time, blood loss, return to normal activities time (RNAT), visual analogue scale (VAS), scar width, wound healing time, cosmetic result, and complications were recorded. RESULTS: There were no significant differences in blood loss, RNAT, or complications between the two groups. There were no significant differences in the VAS scores at theduring operation, and 6 or 24 hours after surgery (P>0.05). The wound scar width was wider in the SR group than in the PCSD group (P<0.01). Patients in the SR group had significantly longer wound healing time compared with those in the PCSD group (P<0.01). Patients who underwent PCSD wereere significantly more satisfied with the cosmetic results (P<0.01). CONCLUSIONS: SR and PCSD are safe and effective minimally invasive techniques for adult male circumcision. Compared with SRs, PCSDs have the advantages of faster postoperative incision healing and a good effect on wound cosmetics.

Asunto(s)

Circuncisión Masculina/instrumentación , Fimosis/cirugía , Técnicas de Sutura/instrumentación , Adolescente , Adulto , Anciano , Circuncisión Masculina/métodos , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dolor Postoperatorio , Estudios Prospectivos , Suturas , Resultado del Tratamiento , Adulto Joven

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Rubber tree is a major commercial source of natural rubber. Latex coagulation is delayed by thiols, which belong to the important type of antioxidants in laticifer submembrane, and is composed of glutathione (GSH), cysteine, and methionine. The rate-limiting enzyme, γ-ECS, plays an important role in regulating the biosynthesis of glutathione under any environment conditions. To understand the relation between γ-ECS and thiols and to correlate latex flow with one-time tapping and continuous tapping, we cloned and derived the full length of one γ-ECS from rubber tree latex (Hbγ-ECS1). According to qPCR analysis, the expression levels of Hbγ-ECS1 were induced by tapping and Ethrel stimulation, and the expression was related to thiols content in the latex. Continuous tapping induced injury, and the expression of HbγECS1 increased with routine tapping and Ethrel-stimulation tapping (more intensive tapping). According to expression in long-term flowing latex, the gene was related to the duration of latex flow. HbγECS1 was expressed in E. coli Rosetta using pET-sumo as an expression vector and the recombinant enzyme was purified; then we achieved 0.827 U/mg specific activity and about 66 kDa molecular weight. The present study can help us understand the complex role of Hbγ-ECS in thiols biosynthesis, which is influenced by tapping.

Asunto(s)

Glutamato-Cisteína Ligasa/genética , Glutamato-Cisteína Ligasa/metabolismo , Hevea/genética , Hevea/metabolismo , Látex/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Clonación Molecular/métodos , Glutatión/genética , Glutatión/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Compuestos de Sulfhidrilo/metabolismo

RESUMEN

Prosthetic heart valve (PHV) dysfunction is rare but potentially life-threatening. Although often challenging, establishing the exact cause of PHV dysfunction is essential to determine the appropriate treatment strategy. In clinical practice, a comprehensive approach that integrates several parameters of valve morphology and function assessed with 2D/3D transthoracic and transoesophageal echocardiography is a key to appropriately detect and quantitate PHV dysfunction. Cinefluoroscopy, multidetector computed tomography, cardiac magnetic resonance imaging, and to a lesser extent, nuclear imaging are complementary tools for the diagnosis and management of PHV complications. The present document provides recommendations for the use of multimodality imaging in the assessment of PHVs.

Asunto(s)

Bioprótesis , Técnicas de Imagen Cardíaca , Ecocardiografía Tridimensional/métodos , Prótesis Valvulares Cardíacas , Guías de Práctica Clínica como Asunto , Brasil , China , Cinerradiografía/métodos , Ecocardiografía/métodos , Ecocardiografía Transesofágica/métodos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Internacionalidad , Imagen por Resonancia Cinemagnética/métodos , Tomografía Computarizada Multidetector/métodos , Imagen Multimodal/métodos , Falla de Prótesis , Sociedades Médicas , Estados Unidos

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Exposure to the fungal pathogen Coccidioides immitis in normal hosts causes primarily self-limited pulmonary disease. We report a case of an immunocompetent patient who developed a Coccidioides-associated iliopsoas abscess with rare intra-abdominal dissemination at least one decade after primary exposure in an area endemic for this fungus.

Asunto(s)

Absceso Abdominal/diagnóstico , Absceso Abdominal/inmunología , Coccidioidomicosis/diagnóstico , Coccidioidomicosis/inmunología , Inmunocompetencia/inmunología , Absceso del Psoas/diagnóstico , Absceso del Psoas/inmunología , Absceso Abdominal/terapia , Adulto , Antibacterianos/administración & dosificación , Coccidioidomicosis/terapia , Drenaje , Humanos , Masculino , México , Epiplón/patología , Absceso del Psoas/terapia , Tomografía Computarizada por Rayos X

RESUMEN

GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive HIV-infected subjects. In the initial study, 10 subjects (8 active and 2 placebo) per dose received sequentially descending GSK2248761 monotherapy regimens of 800, 400, 200, and 100 mg QD for 7 days. Because a dose-response relationship was not identified, a second study examined a lower, 30-mg QD dose in 8 subjects (6 active and 2 placebo). Adverse events, viral load (VL), PK, and reverse transcriptase mutations were assessed and combined for analysis. Treatment with GSK2248761 for 7 days was well tolerated with no serious adverse events or discontinuations. The mean VL reductions from baseline on day 8 were 0.97, 1.87, 1.84, 1.81, and 1.78 log(10) copies/ml for GSK2248761 doses of 30, 100, 200, 400, and 800 mg QD, respectively. GSK2248761 PK (maximum drug concentration in serum [C(max)], area under the plasma concentration-time curve from 0 h to the end of the dosing interval [AUC(0-τ)], and concentration at the end of the dosing interval [C(τ)]) increased proportionally over the dose range of 30 to 800 mg QD. The relationship between short-term VL change and GSK2248761 PK was best described by a maximum-effect (E(max)) model using C(τ) (E(max) = 2.0; 50% effective concentration [EC(50)] = 36.9 ng/ml). No NNRTI resistance mutations emerged during the study. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Transcriptasa Inversa del VIH/antagonistas & inhibidores , VIH-1/efectos de los fármacos , Indoles/uso terapéutico , Ácidos Fosfínicos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Alquinos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/síntesis química , Argentina , Benzoxazinas , Ciclopropanos , Método Doble Ciego , Esquema de Medicación , Farmacorresistencia Viral , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Infecciones por VIH/virología , VIH-1/enzimología , VIH-1/genética , Humanos , Indoles/administración & dosificación , Indoles/síntesis química , Masculino , Mutación , Ácidos Fosfínicos/administración & dosificación , Ácidos Fosfínicos/síntesis química , Placebos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/síntesis química , Carga Viral/efectos de los fármacos

RESUMEN

A supramolecular dual emissive system incorporating two classical copper(I)-cluster-based luminophores, namely, Cu(4)I(4) and Cu(3)Pz(3) (Pz = pyrazolate), is reported. The targeted luminescent coordination polymer exhibits reversible thermochromism spanning from green to orange-red.

Asunto(s)

Cobre/química , Hidrocarburos/química , Sustancias Luminiscentes/química , Polímeros/química , Pirazoles/química , Temperatura , Color , Mediciones Luminiscentes , Modelos Moleculares , Conformación Molecular