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Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.
La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.
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Transtornos de Proteínas de Coagulação , Conjuntivite , Criança , Lactente , Feminino , Humanos , Plasminogênio/genética , Conjuntivite/etiologia , Transtornos de Proteínas de Coagulação/complicações , FibrinaRESUMO
Resumen La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseu do membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se trans mite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitan tes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y ni ños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simu ló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.
Abstract Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the de position of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is trans mitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since child hood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflam matory bowel disease and resolved spontaneously.
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OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
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Norepinefrina , Choque Séptico , Animais , Suínos , Norepinefrina/uso terapêutico , Microcirculação , Circulação Esplâncnica , Vasoconstritores/farmacologia , Vasoconstritores/uso terapêutico , Choque Séptico/tratamento farmacológico , Hemodinâmica , Lactatos/farmacologia , Lactatos/uso terapêuticoRESUMO
Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii. Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid (T1m) caused a decrease in the median inhibitory concentration (IC50) on the K562 cell line. Its mode of action was apparently apoptosis, ROS generation, and loss of mitochondrial membrane potential (MMP). Molecular docking analysis showed T1m to produce lower binding energies than its precursor for the Bcl-2 and EGFR proteins. Small, simple, and viable modifications to triterpenes can improve their activity against leukemia cell lines. T1m is a potentially promising element for future research. Clarifying the targets in its mode of action will improve its applicability.
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Leucemia , Triterpenos , Humanos , Triterpenos/química , Lupanos , Simulação de Acoplamento Molecular , Apoptose , Leucemia/tratamento farmacológico , Linhagem Celular TumoralRESUMO
General anaesthesia is often homologated to physiological sleep whereas they only share some of the same characteristics. The differences are remarkable in electroencephalographic characteristics and in the way in which the state of disconnection from the environment is established. General anaesthesia and surgery are phenomena that alter the physiological cycles of postoperative sleep depending on the drugs used, the neurological depression achieved, the functional reserve of the patient and specific phenomena of neuroinflammation triggered by the surgery. Anaesthesia shares very partially the mechanisms that trigger sleep but shares a common phenomenon: the sleep inertia; They do share a common phenomenon: the inertia of awake- ning, possibly enhanced by anaesthesia in susceptible patients. Given the physiological importance of sleep in the postoperative reparative process, it is essential to recognize which patients are likely to influence their reconnection and to take preventive actions to minimize the impact on postoperative sleep architecture. This article describes the differences and similarities between anaesthetic and physiological sleep, including electroencephalographic differences, the effect of different anaesthetics on postoperative sleep architecture, the phenomenon of common inertia and neuroinflammation.
La anestesia general se la homologado frecuentemente al sueño fisiológico cuando solo comparten algunas de sus características. Las diferencias son llamativas en características electroencefalográficas y en la forma de instalar el estado de desconexión al medio. La anestesia general y la cirugía son fenómenos que alteran los ciclos fisiológicos del sueño posoperatorio dependiendo de las drogas, la depresión neurológica alcanzado, la reserva funcional del paciente y fenómenos específicos de neuroinflama- ción desencadenados por la cirugía. La anestesia comparte muy parcialmente los mecanismos que desencadenan el sueño. Si comparten un fenómeno común: la inercia del despertar, eventualmente potenciada por la anestesia. Dada la importancia fisiológica del sueño en el proceso reparativo post operatorio, son fundamentales el reconocimiento de los pacientes susceptibles de enlentecer su reconexión y eventuales acciones preventivas para minimizar efectos en la arquitectura del sueño posoperatorio y su requerimiento en el proceso de recuperación. El presente artículo, describe las diferencias y similitudes entre el sueño anestésico y el fisiológico, incluyendo las diferencias electroencefalograficas entre ambos, el impacto de diferentes anestésicos en la arquitectura del sueño posoperatorio, el fenómeno de la inercia común, comentando algunas acciones que ayudarían a disminuir estos problemas.
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Humanos , Sono/fisiologia , Anestesia GeralRESUMO
IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.
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COVID-19/complicações , Intubação Intratraqueal/estatística & dados numéricos , Oxigenoterapia/métodos , Oxigênio/uso terapêutico , Insuficiência Respiratória/terapia , Idoso , Idoso de 80 Anos ou mais , COVID-19/terapia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/instrumentação , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , SARS-CoV-2 , Fatores de Tempo , Resultado do TratamentoRESUMO
Secundiflorol G (SG) is an isoflavan isolated from the root bark of Aeschynomene fascicularis, a Mayan medicinal plant used to treat cancer-like symptoms. SG has been shown to have cytotoxic effects on cervical cancer cells (HeLa). Assays were done to identify the mechanisms of SG's cytotoxic effect.HeLa cells treated with SG exhibited early and late apoptosis, and caspase-9, -8 and -3 activities. It also induces generation of reactive oxygen species and disrupted mitochondrial membrane potential.SG isolated from A. fascicularis induces apoptosis through extrinsic and intrinsic pathways on HeLa cells. SG could be a candidate for in vivo studies and a promising natural compound in cervical cancer treatment.
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Apoptose/efeitos dos fármacos , Benzopiranos/isolamento & purificação , Benzopiranos/farmacologia , Fabaceae/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Plantas Medicinais/química , Neoplasias do Colo do Útero/patologia , Antineoplásicos/farmacologia , Benzopiranos/química , Caspases/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ativação Enzimática/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Isoflavonas/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/enzimologia , Proteína X Associada a bcl-2/metabolismoRESUMO
Septic shock involves a complex interaction between abnormal vasodilation, relative and/or absolute hypovolemia, myocardial dysfunction, and altered blood flow distribution to the tissues. Fluid administration, vasopressor support and inotropes, represent fundamental pieces of quantitative resuscitation protocols directed to assist the restoration of impaired tissue perfusion during septic shock. Indeed, current recommendations on sepsis management include the use of inotropes in the case of myocardial dysfunction, as suggested by a low cardiac output, increased filling pressures, or persisting signals of tissue hypoperfusion despite an adequate correction of intravascular volume and mean arterial pressure by fluid administration and vasopressor support. Evidence supporting the use of inotropes in sepsis and septic shock is mainly based on physiological studies. Most of them suggest a beneficial effect of inotropes on macro hemodynamics especially when sepsis coexists with myocardial dysfunction; others, however, have demonstrated variable results on regional splanchnic circulation, while others suggest favorable effects on microvascular distribution independently of its impact on cardiac output. Conversely, impact of inodilators on clinical outcomes in this context has been more controversial. Use of dobutamine has not been consistently related with more favorable clinical results, while systematic administration of levosimendan in sepsis do not prevent the development of multiorgan dysfunction, even in patients with evidence of myocardial dysfunction. Nevertheless, a recent metanalysis of clinical studies suggests that cardiovascular support regimens based on inodilators in sepsis and septic shock could provide some beneficial effect on mortality, while other one corroborated such effect on mortality specially in patients with proved lower cardiac output. Thus, using or not inotropes during sepsis and septic shock remains as controversy matter that deserves more research efforts.
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BACKGROUND: Loss of vascular tone is a key pathophysiological feature of septic shock. Combination of gradual diastolic hypotension and tachycardia could reflect more serious vasodilatory conditions. We sought to evaluate the relationships between heart rate (HR) to diastolic arterial pressure (DAP) ratios and clinical outcomes during early phases of septic shock. METHODS: Diastolic shock index (DSI) was defined as the ratio between HR and DAP. DSI calculated just before starting vasopressors (Pre-VPs/DSI) in a preliminary cohort of 337 patients with septic shock (January 2015 to February 2017) and at vasopressor start (VPs/DSI) in 424 patients with septic shock included in a recent randomized controlled trial (ANDROMEDA-SHOCK; March 2017 to April 2018) was partitioned into five quantiles to estimate the relative risks (RR) of death with respect to the mean risk of each population (assumed to be 1). Matched HR and DAP subsamples were created to evaluate the effect of the individual components of the DSI on RRs. In addition, time-course of DSI and interaction between DSI and vasopressor dose (DSI*NE.dose) were compared between survivors and non-survivors from both populations, while ROC curves were used to identify variables predicting mortality. Finally, as exploratory observation, effect of early start of vasopressors was evaluated at each Pre-VPs/DSI quintile from the preliminary cohort. RESULTS: Risk of death progressively increased at gradual increments of Pre-VPs/DSI or VPs/DSI (One-way ANOVA, p < 0.001). Progressive DAP decrease or HR increase was associated with higher mortality risks only when DSI concomitantly increased. Areas under the ROC curve for Pre-VPs/DSI, SOFA and initial lactate were similar, while mean arterial pressure and systolic shock index showed poor performances to predict mortality. Time-course of DSI and DSI*NE.dose was significantly higher in non-survivors from both populations (repeated-measures ANOVA, p < 0.001). Very early start of vasopressors exhibited an apparent benefit at higher Pre-VPs/DSI quintile. CONCLUSIONS: DSI at pre-vasopressor and vasopressor start points might represent a very early identifier of patients at high risk of death. Isolated DAP or HR values do not clearly identify such risk. Usefulness of DSI to trigger or to direct therapeutic interventions in early resuscitation of septic shock need to be addressed in future studies.
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BACKGROUND: Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS. METHODS: Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production ([Formula: see text]) and CO2 exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after. RESULTS: Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman's rho = - 0.66, p < 0.001; R2 = 0.67, p < 0.001). CONCLUSION: Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.
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BACKGROUND: Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS: A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS: Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION: A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.
Assuntos
Hidratação , Norepinefrina , Choque Séptico , Vasoconstritores , Injúria Renal Aguda/complicações , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Terapia de Substituição Renal , Choque Séptico/tratamento farmacológico , Fatores de Tempo , Vasoconstritores/administração & dosagemRESUMO
INTRODUCTION: (3S)-16,17-Didehydrofalcarinol (1) has been isolated from Tridax procumbens and has proved to have notorious bioactivity against Leishmania mexicana. In this study, hexane fractions obtained from the methanol extract of each plant part (roots, stems, leaves, flowers, and fruits) of T. procumbens collected monthly during a year were analysed in order to determine the quantity of 1 associated with biotic variables. OBJECTIVE: The aim of this study was to find the season of the year in which the bioactive metabolite 1 is at the highest concentration and to correlate it with temperature, length of day light, and rainfall. METHODS: Hexane fractions were obtained by liquid-liquid extraction and an accurate quantitation of 1 was performed using gas chromatography with a flame ionisation detector (GC-FID) employing pelargonic acid vanillyl amide (2) as internal standard. Partial validation was based on linearity and precision. RESULTS: Our results indicated that the total content of 1 has significant variation (P ≤ 0.05) during the different collecting months. The total content of the metabolite reached its highest level in the roots of the plant during June in the rainfall season (0.0358 ± 0.001 mg/g), and its lowest values in February and March during the drought season (0.0015 ± 0.000 and 0.0008 ± 0.000 mg/g, respectively). CONCLUSION: Our study provided evidence that the content of 1 in roots is strongly influenced by the variables of the harvesting season, also indicating that the biosynthesis of the active metabolite is enhanced during the warm and rainy months.
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Extratos Vegetais , Polímero Poliacetilênico , Di-Inos , Álcoois Graxos , Estações do Ano , Distribuição TecidualRESUMO
Urban adaptation to climate change is likely to emerge from the responses of residents, authorities, and infrastructure providers to the impact of flooding, water scarcity, and other climate-related hazards. These responses are, in part, modulated by political relationships under cultural norms that dominate the institutional and collective decisions of public and private actors. The legacy of these decisions, which are often associated with investment in hard and soft infrastructure, has lasting consequences that influence current and future vulnerabilities. Making those decisions visible, and tractable is, therefore, an urgent research and political challenge in vulnerability assessments. In this work, we present a modeling framework to explore scenarios of institutional decision-making and socio-political processes and the resultant effects on spatial patterns of vulnerability. The approach entails using multi-criteria decision analysis, agent-based models, and geographic information simulation. The approach allows for the exploration of uncertainties, spatial patterns, thresholds, and the sensitivities of vulnerability outcomes to different policy scenarios. Here, we present the operationalization of the framework through an intentionally simplified model example of the governance of water in Mexico City. We discuss results from this example as part of a larger effort to empirically implement the framework to explore sociohydrological risk patterns and trade-offs of vulnerability in real urban landscapes.
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Mudança Climática , Inundações , Cidades , Tomada de Decisões , MéxicoRESUMO
Neurological disorders are a public health problem worldwide for which there is currently no direct treatment of the cause of the disorder. The goal of this study was to investigate the potential in vitro neuroprotective property of plants used in Mayan traditional medicine. Plant ethanolic extracts were prepared and tested on models in which neuronal damage was induced by glutamate, i.e., a human neuroblastoma cell line (SH-SY5Y) and rat cortical neurons. HPLC profiles from active extracts were also obtained. A total of 51 plant species were identified in the literature as plant species used in Mayan traditional medicine for the treatment of symptoms suggestive of neurological disorders, and we studied 34 of these in our analysis. Six extracts had a neuroprotective effect on SH-SY5Y cells, with the most active extract being that from Schwenckia americana roots (half maximal effective concentration [EC50] 11.3 ± 2.9 µg/mL), and three extracts exhibited a neuroprotective effect in the rat neuron cortical model, with the most active extract being that from Elytraria imbricata aerial parts (EC50 6.8 ± 3.1 µg/mL). These results suggest that the active extracts from such plants have the potential to be a great resource. Future studies should be performed that are more extensive and which isolate the active constituents.
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Ácido Glutâmico/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/química , Plantas Medicinais/química , Animais , Humanos , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos WistarRESUMO
Current literature shows the association of post-intubation hypotension and increased odds of mortality in critically ill non-trauma and trauma populations. However, there is a lack of research on potential interventions that can prevent or ameliorate the consequences of endotracheal intubation and thus improve the prognosis of trauma patients with post-intubation hypotension. This review paper hypothesizes that the deployment of REBOA among trauma patients with PIH, by its physiologic effects, will reduce the odds of mortality in this population. The objective of this paper is to review the current literature on REBOA and post-intubation hypotension, and, furthermore, to provide a rational hypothesis on the potential role of REBOA in severely injured patients with post-intubation hypotension.
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Aorta , Oclusão com Balão/métodos , Hipotensão/etiologia , Hipotensão/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Choque Hemorrágico/etiologia , Choque Hemorrágico/prevenção & controle , Ferimentos e Lesões/complicações , Hemodinâmica , Humanos , Ressuscitação , Análise de SobrevidaRESUMO
Three new lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxolup-20(29)-en-28-oic acid (2), and 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), together with eight known compounds (4-11) were isolated from a methanol extract of Phoradendron vernicosum aerial parts. The chemical structures of 1-3 were determined on the basis of spectroscopic data interpretation. The isolated compounds were tested against seven human cancer cell lines and two normal cell lines.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Phoradendron/química , Componentes Aéreos da Planta/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células KB , Células MCF-7 , México , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Folhas de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
BACKGROUND: Systemic inflammation is characterised by high circulating levels of inflammatory cytokines and increased macrophage infiltration in peripheral tissues. Most importantly, this inflammatory state does not involve damage or loss of function of the infiltrated tissue, which is a distinctive feature of the low-grade systemic inflammation. The term "meta-inflammation" has also been used to refer to the low-grade systemic inflammation due to its strong relationship with the development of cardio-metabolic diseases in obesity. OBJECTIVE: A review is presented on the recent clinical and experimental evidence concerning the role of adipose tissue inflammation as a key mediator of low-grade systemic inflammation. Furthermore, the main molecular mechanisms involved in the inflammatory polarization of macrophages with the ability to infiltrate both the adipose tissue and the vascular endothelium via activation of toll-like receptors by metabolic damage-associated molecular patterns, such as advanced glycation-end products and oxidized lipoproteins, is discussed. Finally, a review is made of the pathogenic mechanisms through which the low-grade systemic inflammation contributes to develop insulin resistance, dyslipidaemia, atherogenesis, type 2 diabetes, and hypertension in obese individuals. CONCLUSIONS: A better understanding of the molecular mechanisms of low-grade systemic inflammation in promoting cardio-metabolic diseases is necessary, in order to further design novel anti-inflammatory therapies that take into consideration clinical data, as well as the circulating levels of cytokines, immune cells, and metabolic damage-associated molecular patterns in each patient.
Assuntos
Inflamação/complicações , Síndrome Metabólica/etiologia , Obesidade/complicações , Adipocinas/metabolismo , Arteriosclerose/etiologia , Arteriosclerose/fisiopatologia , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Dislipidemias/etiologia , Dislipidemias/fisiopatologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Inflamação/fisiopatologia , Inflamação/terapia , Resistência à Insulina , Células Secretoras de Insulina/patologia , Gordura Intra-Abdominal/fisiopatologia , Leptina/fisiologia , Macrófagos/fisiologia , Síndrome Metabólica/fisiopatologia , Modelos Biológicos , NF-kappa B/metabolismo , Obesidade/fisiopatologia , Receptores de Reconhecimento de Padrão/fisiologia , Receptores Toll-Like/fisiologiaRESUMO
The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer.
Assuntos
Antineoplásicos , Citotoxinas , Fabaceae/química , Casca de Planta/química , Raízes de Plantas/química , Plantas Medicinais/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , HumanosRESUMO
AbstractAphelandra scabra (Vahl) Sm., Acanthaceae, is a shrub widely used by some Mayan communities as carminative, antidote, and remedy for some infections. Bio-guided isolation of the methanol extract of leaves led us to the purification of the anti-giardial metabolites cirsimaritin and sorbifolin, along with the inactive metabolites cirsimarin, sorbifolin-6-O-β-glucopyranoside, and squalene. Cirsimaritin displayed high activity in the anti-giardial bioassay with an IC50 = 3.8 μM, being considered as outstanding when compared to previous reported metabolites, while sorbifolin showed a low activity with an IC50 = 75.6 μM. Additionally, both compounds proved not to be cytotoxic in an in vitro bioassay against HEK-293, a normal cell line. This is the first investigation on anti-giardial properties of A. scabra and its phytochemistry as well, thus the isolated compounds are considered as new for the plant genus and for the species.
RESUMO
Debido al creciente interés actual en la industria del avestruz (Struthio camelus var. domesticus) y al escaso material bibliográfico referente a la morfología del aparato respiratorio, se ha propuesto analizar comparativamente el segmento laringo traqueo siringeo pulmonar de esta especie, con el objeto de contribuir en esta área. El estudio se realizó con seis avestruces clínicamente sanos, de los cuales se obtuvieron muestras representativas del segmento laringo traqueo siringeo pulmonar. Las muestras fueron procesadas de acuerdo a las técnicas histológicas de rutina para luego realizar un análisis morfológico comparativo con la gallina (Gallus gallus). En el avestruz el cartílago aritenoides es par y está situado en posición dorsal y craneal a la laringe. El cartílago cricoides es único, situado en posición ventral y caudal a la laringe. Al igual que en la gallina, presenta un cartílago procricoides. La tráquea presenta un número mayor de anillos que el observado en la gallina. A nivel de la siringe, el pessulus está constituido por un doble pliegue dorsoventral de la membrana mucosa, con una lámina propia de tejido conectivo denso sobre una gruesa capa de tejido adiposo. A diferencia de la gallina, el pessulus del avestruz no presenta tejido cartilaginoso ni óseo. La mucosa situada desde la laringe hasta los bronquios secundarios, posee un epitelio seudoestratificado prismático ciliado con células caliciformes, con criptas y glándulas túbulo-alveolares simples de secreción mucosa. En el caso de los bronquios primarios extrapulmonares esta característica histológica se observa sólo en la región medial, donde se encuentran los extremos de los semianillos de cartílago hialino. La mucosa restante de éstos, sólo posee un epitelio seudoestratificado prismático ciliado con células caliciformes. Los sacos aéreos presentan esta característica histológica en algunos sectores.
Due to the growing interest of the ostrich industry (Struthio camelus var. domesticus) and the scarce bibliographic material related to morphology of the respiratory system of the ostrich, we carried out a comparative analysis of the laryngotracheal pulmonary segment of this bird. The research was conducted in six clinically healthy ostriches from which representative samples of the laryngotracheal pulmonary segment were obtained. Samples were processed using standard histological technique and a comparative morphological analysis between ostriches and chicken (Gallus gallus) was performed. In the ostrich, the arytenoid cartilage is double and placed in a dorsal and cranial position in relation to the larynx while the cricoid cartilage is single and situated in a ventral and caudal position. Like the chicken, the procricoid cartilage is also present. The trachea exhibits a greater number of rings compared to the chicken. At the syrinx level, the pessulus is made up of a dorso-ventral double-fold of mucous membrane with a lamina propria of dense connective tissue over a thick adipose layer. Unlike the chicken the ostrich pessulus does not contain any ossified or cartilaginous tissues. The mucosa between the larynx and secondary bronchi has a pseudostratified prismatic ciliated epithelium with mucous goblet cells with crypts and simple tubuloalveolar mucosal glands for mucous secretion. In the extrapulmonary primary bronchi this histological feature is observed only in the medial aspect where the ends of the cartilaginous rings are found. The remaining mucosa of these bronchi has a pseudostratified prismatic ciliated epithelium with mucous goblet cells. Aerial sacs show this histological feature in some sectors.