RESUMO
Six novel click-tambjamines (1-6) bearing an alkyl chain of varying length linked to the imine moiety have been formulated in nanostructured lipid carriers (NLCs) to evaluate their transmembrane anion transport activity both when free (i.e., not encapsulated) and nanoformulated. Nanostructured lipid carriers (NLCs) are an example of drug delivery systems (DDSs) that stand out because of their versatility. In this work we show that NLCs can be used to efficiently formulate highly lipophilic anionophores and experiments conducted in model liposomes reveal that these formulations are adequate to deliver anionophores without compromising their transport activity. This result paves the way to facilitate the study of highly lipophilic anionophores and their potential use as future drugs.
Assuntos
Portadores de Fármacos , Nanoestruturas , Sistemas de Liberação de Medicamentos , Lipossomos , Lipídeos , Tamanho da PartículaRESUMO
Coffee presents beneficial health properties, including antiobesity effects. However, its effects on inflammation are controversial. Hydroxycinnamic acids are the main coffee phenolic bioactive compounds. In human bioavailability studies carried out with coffee, among the most abundant compounds found in urine and plasma were the colonic metabolites, dihydrocaffeic (DHCA), dihydroferulic (DHFA), and hydroxyhippuric (HHA) acids. To understand the hepato-protective potential of these three compounds, we tested whether treatment with realistic concentrations (0.5-10 µM) were effective to counteract inflammatory process and oxidative status induced by tumor necrosis factor α (TNF-α). First, we established a novel model of inflammation/oxidation using TNF-α and HepG2 cells. Afterwards, we evaluated the activity of DHCA, DHFA, and HHA against the inflammatory/oxidative challenge through the determination of the inflammatory mediators, interleukins (IL)-6, and IL-8 and chemokines, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1, as well as the levels of biomarkers of oxidative stress, such as reactive oxygen species, reduced glutathione, and the antioxidant enzymes glutathione peroxidase and reductase. Results showed that all three compounds have a potential hepato-protective effect against the induced inflammatory/oxidative insult.
Assuntos
Café , Fenóis , Humanos , Fenóis/farmacologia , Fenóis/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Hepatócitos/metabolismo , Glutationa Peroxidase/metabolismo , Interleucina-6/metabolismo , InflamaçãoRESUMO
Obesity is coupled with an altered redox state and low-level inflammation. Oxidative stress may increase pre-adipocyte proliferation, adipocyte differentiation and mature adipocyte size. Regarding inflammation, the dysregulation of cytokine production by adipose tissue takes place in obesity, which is promoted by oxidative stress. Polyphenols may exert a positive effect on obesity, not only by modulating the redox state, but also due to their anti-inflammatory activity. Coffee, which is one of the most consumed beverages, is very rich in phenolic compounds. Bioavailability studies on coffee phenols have shown that the most abundant group of metabolites in plasma and urine are dihydrocaffeic (DHCA), dihydroferulic (DHFA), and hydroxyhippuric (HHA) acids, the three acids of colonic origin. To better understand the antioxidant and anti-inflammatory properties of DHCA, DHFA, and HHA, an inflammation/oxidation model was set up in the pre-adipocyte 3T3-L1 cell line using tumor necrosis factor-α (TNF-α). After the exposure of 3T3-L1 cells to 0.5, 1, 5, and 10 µM of TNF-α at different times, the cell viability, interleukin (IL)-6 secretion, and the production of reactive oxygen species (ROS) and glutathione (GSH) were determined. Using the TNF-α prooxidant and proinflammatory conditions established (10 µM, 24 h), it was observed that the physiological concentrations (0.5, 1, 5, and 10 µM) of DHCA, DHFA, and HHA induced dose-dependent antioxidant effects according to the ROS, GSH, and antioxidant enzyme (glutathione peroxidase) results. In addition, reductions in the IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1) concentrations were observed to different extents depending on the metabolite (DHFA, HHA, or DHCA) and the concentration used. In conclusion, the main colonic metabolites from coffee chlorogenic acids may counteract TNF-α-induced inflammation and oxidative stress in the 3T3-L1 cell line, and thus, they present antiobesity potential.
Assuntos
Ácido Clorogênico , Café , Camundongos , Animais , Ácido Clorogênico/farmacologia , Antioxidantes/farmacologia , Fator de Necrose Tumoral alfa , Espécies Reativas de Oxigênio , Células 3T3-L1 , Estresse Oxidativo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , ObesidadeRESUMO
INTRODUCTION: Asthma is a heterogeneous disease characterized by multiples respiratory symptoms; this is a polygenic entity that involves a complex interaction of environmental factors and inherent to the individual. To understand the development of asthma, some phenotypes have been proposed. OBJECTIVE: This work's purpose was to explore different molecules related to asthma development and to define each phenotype's specific characteristics. MATERIAL AND METHODS: 96 adult patients diagnosed with asthma before any treatment were enrolled in the protocol. Spirometric parameters, circulating leukocytes, serum IgE, body mass index, exhaled nitric oxide (FENO), and leukotrienes (LTB4) in urine were determined in each patient. The presence of asthma phenotypes proposed by the Global Initiative for Asthma (GINA) were explored: A) Allergic asthma, B) Non-allergic asthma, C) Late-onset asthma, D) Asthma with persistent airflow limitation, and E) Asthma with overweight and obesity. RESULTS: In the cohort analyzed, we found four of phenotypes proposed by GINA; however, these phenotypes overlapped, due to this, 4 groups were integrated with allergic, non-allergic and obese patients, which were the main phenotypes. The main overlap was that of patients not-obese allergic, and was characterized by earlier onset, elevated levels of IgE, LTB4 and inflammasome related cytokines. Non-allergic patients had a significant association between interleukin (IL)-18 and IL-18 binding protein (BP) with narrow ratio between these cytokines. Finally, LTB4 had remarkable capacity to discriminate between allergic and not allergic patients. CONCLUSIONS: Asthmatic phenotypes exist as interrelated characteristics and not as discrete entities. High levels of leukotrienes and IgE are hallmarks in the allergic phenotype of asthma.
Assuntos
Asma/genética , Asma/patologia , Adulto , Idade de Início , Asma/sangue , Asma/diagnóstico , Biomarcadores/sangue , Citocinas/sangue , Eosinófilos/metabolismo , Feminino , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/complicações , Imunoglobulina E/sangue , Inflamassomos/sangue , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Interleucina-18/sangue , Interleucina-8/sangue , Leucotrienos/urina , Masculino , Pessoa de Meia-Idade , Sobrepeso , Fenótipo , Fator de Crescimento Transformador beta/sangueRESUMO
The use of arylglyoxal as starting material in Passerini and Ugi reactions affords ß-ketoamides. This has allowed to study keto-enol tautomerism in these systems and assess the way in which the presence of acyloxy or aminoacyl groups bound to the C2 position affects such tautomerism, and to investigate the reactivity of both the enol and carbonyl forms. In this work we also prove the versatility of the Passerini reaction, since depending on the conditions to which the corresponding adducts are subjected different products of synthetic interest can be obtained.
Assuntos
Aldeídos/química , Amidas/química , Técnicas de Química Sintética/métodos , Química Farmacêutica/métodos , Glioxal/química , Estrutura MolecularRESUMO
Findings of several experiments indicate that many treatments that typically interfere with memory consolidation are ineffective in preventing or attenuating memory induced by intense training. As extensive evidence suggests that the consolidation of newly acquired memories requires gene expression and de novo protein synthesis the present study investigated whether intense training prevents consolidation impairment induced by blockers of mRNA and protein synthesis. Rats were given a single inhibitory training trial using a moderate (1.0â¯mA) or a relatively intense (2.0â¯mA) foot-shock. Bilateral hippocampal infusions of the mRNA synthesis blocker DRB (10, 40 or 80â¯ng/0.5⯵L/hemisphere) or the protein synthesis inhibitor anisomycin (ANI), an inhibitor de novo protein synthesis (15.62, 31.25, or 62.50⯵g/0.5⯵L/hemisphere) were administered 15â¯min prior to training. Retention was measured at 30â¯min or 48â¯h following training. DRB and ANI impaired memory of moderate training in a dose-dependent manner without affecting short-term memory. In contrast, memory consolidation was not impaired in the groups trained with 2.0â¯mA. The findings showed that: (1) inhibitors of transcription and translation in the hippocampus impair the consolidation of memory of inhibitory avoidance learning induced by moderate levels of aversive stimulation and (2) blocking of mRNA and protein synthesis does not prevent the consolidation of memory induced by relatively high levels of aversive stimulation. These findings do not support the hypothesis that gene expression and de novo protein synthesis are necessary steps for long-term memory formation as memory was not impaired if intense foot-shock was used in training.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Animais , Anisomicina/farmacologia , Aprendizagem da Esquiva/fisiologia , Diclororribofuranosilbenzimidazol/farmacologia , Eletrochoque , Hipocampo/fisiologia , Masculino , Consolidação da Memória/fisiologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos WistarRESUMO
It has been found that interference with neural activity after a consolidated memory is retrieved produces an amnestic state; this has been taken has indicative of destabilization of the memory trace that would have been produced by a process of reconsolidation (allowing for maintenance of the original trace). However, a growing body of evidence shows that this is not a reliable effect, and that it is dependent upon some experimental conditions, such as the age of the memory, memory reactivation procedures, the predictability of the reactivation stimulus, and strength of training. In some instances, where post-retrieval treatments induce a retention deficit (which would be suggestive of interference with reconsolidation), memory is rescued by simple passing of time or by repeated retention tests. We now report that post-training and post-retrieval inhibition of transcription and translation in dorsal striatum, a structure where both of these manipulations have not been studied, produce interference with consolidation and a transitory retention deficit, respectively. These results do not give support to the reconsolidation hypothesis and lead to the conclusion that the post-activation deficiencies are due to interference with retrieval of information.
Assuntos
Corpo Estriado/metabolismo , Consolidação da Memória/efeitos dos fármacos , Memória/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Transcrição Gênica/efeitos dos fármacos , Animais , Anisomicina/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , DNA/biossíntese , Diclororribofuranosilbenzimidazol/farmacologia , Masculino , RNA/biossíntese , Ratos WistarRESUMO
This work studies the sequential execution of dilute sulfuric acid (DAP) (0.1-0.75 %, v/v) and dilute sodium hydroxide (AKP) (0.25-3 %, w/v) [i.e., DAP followed by AKP (DAP+AKP) and vice versa (AKP+DAP)] at low temperatures (<121 °C) and short reaction times (5-60 min) for maximizing sugar recovery in the enzymatic hydrolysis of wheat straw with low enzyme dosage. The pretreatment effectiveness was measured by the sum of the severity factors of both pretreatments and the saccharification yield achieved in the subsequent stage of enzymatic hydrolysis. Degradation compounds were quantified and mass balance calculations were carried out for each pretreatment sequence to verify the correct account of the input biomass and output products. Results show that sequential pretreatments (AKP+DAP and DAP+AKP) had a positive effect in enzyme accessibility thus improving monosaccharide yields compared to single DAP and AKP pretreatments. DAP+AKP achieved a high xylose yield (ca. 0.867 of theoretical) at the DAP stage, while no xylose monosaccharides were detected in the subsequent AKP. After enzyme saccharification of double-pretreated solids, the total monosaccharide yield was 0.786 (of theoretical). For AKP+DAP sequence, lower results were obtained (total monosaccharide yield 0.783 of theoretical). Sequential pretreatments total yields increased by 21 % compared to single pretreatments. AKP removed more than half of the lignin from the wheat straw in all cases. Acid and alkali concentrations played a relevant role in all pretreatment sequences, while reaction time and temperature were less important with an almost-linear effect on the total monosaccharide yields.
Assuntos
Enzimas/metabolismo , Triticum/metabolismo , Biomassa , HidróliseRESUMO
There is extensive evidence that amnestic treatments are less effective, or ineffective when administered to subjects that have been overtrained or subjected to high foot-shock intensities in aversively motivated learning. This protective effect has been found with a variety of learning tasks and with treatments that disrupt activity in several regions of the brain, including the hippocampus, amygdala, striatum, and substantia nigra. Such findings have been interpreted as suggesting that the brain regions disrupted are not critical sites for the memory processes induced by these types of training. In most experiments investigating this issue the amnestic treatments were administered after training. Thus, it might be less amnesia was induced because the training accelerated memory consolidation and, thus, the maximum effect of the amnestic treatment occurred after memory of the learning experience was consolidated. This study investigated this issue by inactivating the hippocampus of rats bilaterally with tetrodotoxin (TTX) (10 ng/side) 30 min before one-trial inhibitory avoidance training using relatively low (1.0 mA), medium (2.0 mA), or high (3.0 mA) foot-shock intensities. Retention of the task was measured 48 h after training. TTX produced a profound retention deficit, a mild deficit, and no deficit at all in the 1.0, 2.0, and 3.0 mA groups, respectively. These data confirm the protective effect of training with relatively high foot-shock intensity against experimentally induced amnesia, and suggests that this protection is not due to accelerated consolidation. Rather, the findings suggest that strong training activates brain systems other than those typically involved in mediating memory consolidation.
Assuntos
Aprendizagem da Esquiva/fisiologia , Habituação Psicofisiológica/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Amnésia/induzido quimicamente , Animais , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Bloqueadores dos Canais de Sódio/toxicidade , Tetrodotoxina/toxicidadeRESUMO
Background: Among emerging AI technologies, Chat-Generative Pre-Trained Transformer (ChatGPT) emerges as a notable language model, uniquely developed through artificial intelligence research. Its proven versatility across various domains, from language translation to healthcare data processing, underscores its promise within medical documentation, diagnostics, research, and education. The current comprehensive review aimed to investigate the utility of ChatGPT in urology education and practice and to highlight its potential limitations. Methods: The authors conducted a comprehensive literature review of the use of ChatGPT and its applications in urology education, research, and practice. Through a systematic review of the literature, with a search strategy using databases, such as PubMed and Embase, we analyzed the advantages and limitations of using ChatGPT in urology and evaluated its potential impact. Results: A total of 78 records were eligible for inclusion. The benefits of ChatGPT were frequently cited across various contexts. In educational/academic benefits mentioned in 21 records (87.5%), ChatGPT showed the ability to assist urologists by offering precise information and responding to inquiries derived from patient data analysis, thereby supporting decision making; in 18 records (75%), advantages comprised personalized medicine, predictive capabilities for disease risks and outcomes, streamlining clinical workflows and improved diagnostics. Nevertheless, apprehensions were expressed regarding potential misinformation, underscoring the necessity for human supervision to guarantee patient safety and address ethical concerns. Conclusion: The potential applications of ChatGPT hold the capacity to bring about transformative changes in urology education, research, and practice. AI technology can serve as a useful tool to augment human intelligence; however, it is essential to use it in a responsible and ethical manner.
Assuntos
Inteligência Artificial , Urologia , Humanos , Urologia/educação , Atenção à SaúdeRESUMO
A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning experience; this effect has been observed after systemic and local administration of amnestic drugs into several brain areas, including the striatum. However, the effects of amnestic treatments on the process of extinction after intense training have not been studied. Previous research demonstrated increased spinogenesis in the dorsomedial striatum, but not in the dorsolateral striatum after intense training, indicating that the dorsomedial striatum is involved in the protective effect of intense training. To investigate this issue, male Wistar rats, previously trained with low, moderate, or high levels of foot shock, were used to study the effect of tetrodotoxin inactivation of dorsomedial striatum on memory consolidation and subsequent extinction of inhibitory avoidance. Performance of the task was evaluated during seven extinction sessions. Tetrodotoxin produced a marked deficit of memory consolidation of inhibitory avoidance trained with low and moderate intensities of foot shock, but normal consolidation occurred when a relatively high foot shock was used. The protective effect of intense training was long-lasting, as evidenced by the high resistance to extinction exhibited throughout the extinction sessions. We discuss the possibility that increased dendritic spinogenesis in dorsomedial striatum may underly this protective effect, and how this mechanism may be related to the resilient memory typical of post-traumatic stress disorder (PTSD).
Assuntos
Aprendizagem da Esquiva , Corpo Estriado , Extinção Psicológica , Ratos Wistar , Tetrodotoxina , Animais , Masculino , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Ratos , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Corpo Estriado/fisiologia , Corpo Estriado/efeitos dos fármacos , Tetrodotoxina/farmacologia , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Amnésia/fisiopatologia , Amnésia/prevenção & controle , EletrochoqueRESUMO
Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months. Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.
El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.
Assuntos
Aedes , Dengue , Criança , Animais , Humanos , Feminino , Dengue/complicações , Dengue/diagnóstico , Dengue/epidemiologia , Fatores de Risco , Diagnóstico Diferencial , ArgentinaRESUMO
BACKGROUND: Loxoscelism is a toxic clinical condition caused by the bite of spiders of the genus Loxosceles, with wide distribution throughout the world.1 Phospholipase D is responsible for dermonecrosis, inflammation, platelet aggregation, hemolysis, alteration of vascular permeability, cytotoxicity, nephrotoxicity, acute renal failure, among other symptoms involved with this protein. CASE REPORT: 27-year-old male patient, who began with a sudden episode of intense pain in the right hand, in the metacarpus and metacarpophalangeal joints. On clinical examination, the upper extremity was noted to have increased volume, extensive edema, hyperemia, and increased local temperature; The lesion progressed to extensive necrosis. Fasciotomies were performed, from distal to proximal, and release of the second and third finger compartment through longitudinal radial and ulnar incisions. A skin autograft was placed, obtained from the anterior surface of the right thigh. Opioid analgesics, non-steroidal anti-inflammatory drugs, corticosteroids, and antibiotics were administered. The skin biopsy reported: inflammatory infiltrate with neutrophils, ulceration, and bacterial colonies. After 27 days he had a favorable evolution, so he was discharged to his home, with follow-up by staff from the Outpatient Service. CONCLUSION: Cutaneous loxoscelism, as a cause of acute compartment syndrome of the hand, is rare, but should be considered in an area endemic for Loxosceles spp. Surgical decompression of the affected compartments represents a decisive factor in the treatment of patients.
ANTECEDENTES: El loxoscelismo es un cuadro clínico tóxico provocado por la mordedura de arañas del género Loxosceles, con amplia distribución en todo el mundo.1 La fosfolipasa D es la responsable de la dermonecrosis, inflamación, agregación plaquetaria, hemólisis, alteración de la permeabilidad vascular, citotoxicidad, nefrotoxicidad, insuficiencia renal aguda, entre otros síntomas implicados con esta proteína. REPORTE DE CASO: Paciente masculino de 27 años, que inició con un cuadro repentino de dolor intenso en la mano derecha, en el metacarpo y las articulaciones metacarpofalángicas. Al examen clínico, la extremidad superior se percibió con aumento de volumen, edema extenso, hiperemia y aumento de la temperatura local; la lesión progresó a necrosis extensa. Se realizaron fasciotomías, de distal a proximal, y liberación del compartimento del segundo y tercer dedo a través de incisiones longitudinales radiales y cubitales. Se colocó un autoinjerto de piel, obtenido de la superficie anterior del muslo derecho. Se administraron analgésicos opioides, antiinflamatorios no esteroides, corticosteroides y antibióticos. La biopsia de piel reporto: infiltrado inflamatorio con neutrófilos, ulceración y colonias bacterianas. Luego de 27 días tuvo evolución favorable, por lo que se dio alta a su domicilio, con seguimiento por personal del servicio de Consulta externa. CONCLUSIÓN: El loxoscelismo cutáneo, como causa de síndrome compartimental agudo de la mano, es poco común, pero debe considerarse en un área endémica para Loxosceles spp. La descompresión quirúrgica de los compartimentos afectados representa un factor decisivo en el tratamiento de los pacientes.
Assuntos
Picada de Aranha , Humanos , Masculino , Adulto , Picada de Aranha/complicações , Doença Aguda , Síndromes Compartimentais/etiologiaRESUMO
BACKGROUND: The first report of cerebrospinal fluid rhinorrhea (CSFR) was described in 1679. In 1826 it was reported that one of the possible causes of CSFR was a fistula between the subarachnoid space and the nasal cavity. In 1903, chemical analysis of the fluid was proposed as a diagnostic criterion. In Mexico there has been 32 case reports. CASE REPORT: Forty-nine years old female with a history of nasal polyposis, profuse rhinorrhea and cephalea who attends the allergy department with the suspicion of allergic rhinitis. After anamnesis and physical evaluation, CSFR was suspected. Chemical analysis of the fluid, head CT and biopsy of nasal polyp were performed. An etmoidal fistula associated with carcinoma was confirmed. CONCLUSIONS: Spontaneous fistulas are rare but can erosionate the bone and adjacent tissues. Diagnosis is based on the clinical findings, patient's history and complementary studies such as beta-2-transferrin determination in nasal fluid.
ANTECEDENTES: En 1679 se describió el primer caso de rinorrea de líquido cefalorraquídeo. En 1826 se reportó como causa una fistula entre el espacio subaracnoideo y la cavidad nasal. Para 1903 se propuso el análisis químico como criterio diagnóstico. En México sólo se han reportado 32 casos de rinorrea de líquido cefalorraquídeo. REPORTE DE CASO: Paciente femenina de 49 años, con antecedente de poliposis nasal, rinorrea abundante y cefalea, quien acudió a consulta para descartar rinitis alérgica. Luego de la anamnesis y la exploración física se sospechó de fuga de líquido cefalorraquídeo secundaria a fístula nasal. Con la histoquímica de moco, tomografía de cráneo y biopsia del pólipo nasal se estableció el diagnóstico de fístula etmoidal secundaria a carcinoma. CONCLUSIÓN: La fístulas espontáneas son excepcionales, pueden erosionar el hueso y los tejidos adyacentes. El diagnóstico se establece con la historia clínica y los antecedentes médicos, además de estudios complementarios y la determinación de Beta-2-transferrina en moco.
Assuntos
Rinorreia de Líquido Cefalorraquidiano , Humanos , Feminino , Rinorreia de Líquido Cefalorraquidiano/etiologia , Pessoa de Meia-Idade , Seio Etmoidal , Neoplasias dos Seios Paranasais/complicaçõesRESUMO
BACKGROUND: Early detection is crucial to improve lung cancer survival rates. Delays in diagnosis might negatively impact the prognosis of the disease. This study aims to analyze the diagnostic delay in lung cancer patients and describe if there is an association between delay and survival. METHODS: The data source used was the Thoracic Tumor Registry of the Spanish Lung Cancer Group. This analysis was restricted to lung cancer cases with information on the first date of consultation by symptoms and date of diagnosis. The delay was calculated as the number of days between the two dates. A descriptive analysis was performed, and ordinal logistic regressions were fitted with delay as the dependent variable. Kaplan-Meier survival analysis and Cox regression were performed. RESULTS: 22,755 lung cancer cases were included. Never smokers were 1.16 (95%CI: 1.06-1.27) times more likely to register longer delay than smokers. Stage 0-I-II cases had a 3.09 (95%CI: 2.88-3.32) higher risk of longer delay compared to III-IV stages. Overall, 5-year survival rate after diagnosis was 23.64% (95%CI: 22.88-24.41). In those categorized as having the shortest delay 5-year survival was 17.67% (95%CI: 16.31-19.07) and in the extreme delay it was 32.98% (95%CI: 31.28-34.69) (p<0.001). Adjusted mortality risk was higher in those with the shortest delay (HR 1.36, CI95%: 1.30-1.43) in comparison with the extreme delay. CONCLUSIONS: Diagnostic delay is short among Spanish lung cancer patients, indicating a relatively quick diagnostic process. Extreme delays appear to be associated with higher survival rates, possibly attributed to slow-growing tumors, earlier stage at diagnosis or basically the natural history of this disease.
RESUMO
INTRODUCTION: The aim of this study was to analyze the clinical and genetic characteristics of young lung cancer cases, and to compare them with those of older cases. METHODS: We used the Thoracic Tumors Registry (TTR) as a data source representative of lung cancer cases diagnosed in Spain, and included all cases registered until 9/01/2023 which had information on age at diagnosis or the data needed to calculate it. We performed a descriptive statistical analysis and fitted logistic regressions to analyze how different characteristics influenced being a younger lung cancer patient. RESULTS: A total of 26,336 subjects were included. Lung cancer cases <50 years old had a higher probability of being women (OR: 1.38; 95% CI: 1.21-1.57), being in stage III or IV (OR: 1.32; 95% CI: 1.08-1.62), not having comorbidities (OR: 5.21; 95% CI: 4.59-5.91), presenting with symptoms at diagnosis (OR: 1.53; 95% CI: 1.29-1.81), and having ALK translocation (OR: 7.61; 95% CI: 1.25-46.32) and HER2 mutation (OR: 5.71; 95% CI: 1.34-24.33), compared with subjects ≥50 years. Among subjects <35 years old (n=61), our study observed a higher proportion of women (59.0% vs. 26.6%; p<0.001), never smokers (45.8% vs. 10.3%; p<0.001), no comorbidities (21.3% vs. 74.0%; p<0.001); ALK translocation (33.3% vs. 4.4%; p<0.001) and ROS1 mutation (14.3% vs. 2.3%; p=0.01), compared with subjects ≥35 years. CONCLUSIONS: Lung cancer displays differences by age at diagnosis which may have important implications for its clinical management.
Assuntos
Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , Receptores ErbB/genética , Proteínas Proto-Oncogênicas/genética , MutaçãoRESUMO
BACKGROUND: Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. AIMS: The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. METHODS AND RESULTS: Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her-2-neu, Ki-67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL-4 (130.5 pg/mL (116-135 pg/mL)), IL-5 (202 pg/mL (191-213 pg/mL)), and IL-13 (105.5 pg/mL (98-117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL-6 (86 pg/mL (79-90 pg/mL)) and INF-γ (93 pg/mL (79-99 pg/mL)). CONCLUSION: Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Hipersensibilidade , Humanos , Feminino , Células Th2 , Neoplasias da Mama/diagnóstico , Antígenos de Neoplasias , Citocinas , Carcinoma Ductal de Mama/diagnóstico , Imunoglobulina ERESUMO
Introduction: Given the limited number of patients in Latin America who have received a booster dose against the COVID-19, it remains crucial to comprehend the effectiveness of different vaccine combinations as boosters in real-world scenarios. This study aimed to assess the real-life efficacy of seven different vaccine schemes against COVID-19, including BNT162b2, ChAdOx1-S, Gam-COVID-Vac, and CoronaVac as primary schemes with either BNT162b2 or ChAdOx1-S as booster vaccines. Methods: In this multicentric longitudinal observational study, participants from Mexico and Argentina were followed for infection and SARS-CoV-2 Spike 1-2 IgG antibodies during their primary vaccination course and for 185 days after the booster dose. Results: A total of 491 patients were included, and the booster dose led to an overall increase in the humoral response for all groups. Patients who received BNT162b2 exhibited the highest antibody levels after the third dose, while those with primary Gam-COVID-Vac maintained a higher level of antibodies after six months. Infection both before vaccination and after the booster dose, and Gam-COVIDVac + BNT162b2 combination correlated with higher antibody titers. Discussion: The sole predictor of infection in the six-month follow-up was a prior COVID-19 infection before the vaccination scheme, which decreased the risk of infection, and all booster vaccine combinations conveyed the same amount of protection.
Assuntos
Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Humanos , Argentina , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Feminino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , México , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Adulto , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Seguimentos , Idoso , Estudos Longitudinais , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Eficácia de Vacinas , ChAdOx1 nCoV-19/imunologia , Vacinas SintéticasRESUMO
BACKGROUND: The SARS-CoV-2 pandemic brought a radical shift in the healthcare system and suboptimal care for vulnerable patients, such as those with Type 2 Diabetes Mellitus (T2D). Therefore, we compared metabolic control and macro/microvascular complications of patients with T2D before and throughout the three-year SARS-CoV-2 pandemic. RESEARCH DESIGN AND METHODS: A retrospective observational cohort of subjects with T2D studied from 2018 to 2022 in Northern Mexico was treated by a dynamic multidisciplinary team. Levels of Glycated hemoglobin (HbA1c), fasting serum glucose (FG), LDL-Cholesterol (LDL-C), blood pressure (BP), albuminuria, triglycerides, Body Mass Index (BMI), and FIB-4 score, micro and macrovascular complications were evaluated. RESULTS: A total of 999 patients were studied, 51.7% males with a mean (SD) age of 60.1 (12.7) years. Adequate glycemic control based on HbA1c increased by 15.2% and 42.3% in FSG (p < 0.001) between the beginning 2018 and the end of 2022. LDL-C control decreased by 5.1% between 2018 and 2022 (p < 0.001). Systolic BP control decreased by 2.6% (p < 0.001), whereas diastolic BP control increased by 1.8% (p = 0.01) between 2018 and 2022. Albuminuria control increased by 8.5% (p = 0.002). When comparing the Area Under the Curve (AUC) of metabolic parameters between patients who developed SARS-CoV-2 vs. those who did not, AUC was statistically higher in those who developed SARS-CoV-2 (p < 0.05). Diabetic neuropathy was the most prevalent microvascular complication (n = 35; 3.6%); ischemic heart disease was the most frequent macrovascular complication (n = 11;1.1%). CONCLUSIONS: A multidisciplinary dynamic team that adapts to the pandemic SARS-CoV-2 maintains and increases metabolic control in subjects with type 2 diabetes in Mexico. This represents a low percentage of chronic complications. The AUC of metabolic parameters of subjects with SARS-CoV-2 infection is higher, reflecting more variability in metabolic control.