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Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract and display few treatment options in advanced stages. Despite increased knowledge of HNSCC molecular biology, the identification of new players involved in triggering HNSCC recurrence and metastatic disease is needed. We uncover that G-protein-coupled receptor kinase-2 (GRK2) expression is reduced in undifferentiated, high-grade human HNSCC tumors, whereas its silencing in model human HNSCC cells is sufficient to trigger epithelial-to-mesenchymal transition (EMT) phenotypic features, an EMT-like transcriptional program and enhanced lymph node colonization from orthotopic tongue tumors in mice. Conversely, enhancing GRK2 expression counteracts mesenchymal cells traits by mechanisms involving phosphorylation and decreased functionality of the key EMT inducer Snail1. Our results suggest that GRK2 safeguards the epithelial phenotype, whereas its downregulation contributes to the activation of EMT programs in HNSCC.
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Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/enzimologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Quinase 2 de Receptor Acoplado a Proteína G/biossíntese , Quinase 2 de Receptor Acoplado a Proteína G/genética , Neoplasias de Cabeça e Pescoço/genética , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Fosforilação , Fatores de Transcrição da Família Snail/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Perinatal Asphyxia (PA) is a leading cause of motor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-α+IFN-γ (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °C for 21 min. Thereafter, 16 µL of MSC-S (containing 6 µg of protein derived from 2 × 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-κB/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia.
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Asfixia Neonatal/terapia , Hipocampo/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Fármacos Neuroprotetores/farmacologia , Administração Intranasal , Animais , Índice de Apgar , Asfixia Neonatal/patologia , Comportamento Animal , Morte Celular/efeitos dos fármacos , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Inflamação/patologia , Inflamação/terapia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos WistarRESUMO
BACKGROUND: Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP) enzymes to vasoactive metabolites (mainly epoxyeicosatrienoic acids) which are known to play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms along these metabolic routes may play a role in the outcome of renal transplantation. DESIGN: One-hundred and forty Caucasian renal transplant recipients and 137 donors were included. We determined the presence of seven common functional polymorphisms in the five genes governing the CYP-mediated AA metabolic pathway (CYP2C8, CYP2C9, CYP2J2, CYP4A11 and CYP4F2). Associations with parameters and events related to graft function and survival were retrospectively investigated throughout the first year after grafting. RESULTS: The CYP2J2*7 allele of the donor was significantly associated with higher risk for delayed graft function [OR = 4·40 (1·45-13·37), P < 0·01] and lower death-censored graft survival [107·90 (84·19-131·62) vs. 176·89 (166·47-187·32) months for CYP2J2*1/*1 grafts; log-rank P = 0·015]. In addition, patients whose donors carried the CYP4A11 434S variant of the F434S polymorphism displayed impaired creatinine clearance, with statistically significant differences vs. 434FF subjects throughout the whole period of study (P < 0·05, P < 0·01, P < 0·001 and P < 0·05 for 1 week, 1 month, 5 months and 1 year after grafting, respectively). CONCLUSIONS: Taken together, these results indicate that variability in the CYP450 genes involved in the synthesis of eicosanoids from AA may have a significant impact on graft function and survival in renal transplantation.
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Ácido Araquidônico/genética , Sistema Enzimático do Citocromo P-450/genética , Transplante de Rim , Polimorfismo Genético/genética , Adulto , Aloenxertos/fisiologia , Ácido Araquidônico/metabolismo , Citocromo P-450 CYP2J2 , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Genótipo , Sobrevivência de Enxerto , Homozigoto , Humanos , Nefropatias/genética , Nefropatias/metabolismo , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
(1) Background: This study aims to evaluate the efficacy and safety of non-thermal plasma (NTP) therapy in accelerating wound healing in patients who have undergone laparoscopic and open surgeries. (2) Methods: NTP was applied using a needle-type reactor with an irradiance of 0.5 W/cm2 on the surgical wounds of fifty patients after obtaining informed consent. Three NTP treatments, each lasting three minutes, were administered hourly. (3) Results: The pilot study showed that NTP-treated surgical wounds healed completely without any signs of infection, dehiscence, pain, or itching. Notably, patients reported minimal pain after the NTP treatment. Visual assessments conducted twenty-four hours after surgery revealed no redness or fluid discharge. Comparisons with traditionally sutured wounds indicated that NTP-treated wounds healed at a rate equivalent to seven days. (4) Conclusions: The application of NTP in laparoscopic and open wounds proved safe and effective, expediting the wound healing process and eliminating clinical risks post-surgery. Significantly, NTP facilitated a healing rate within twenty-four hours, equivalent to seven days for suture-treated wounds, significantly reducing the hospitalization time to a single day. These findings highlight the potential of NTP to be a transformative approach for promoting postoperative recovery.
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Anal fistula, characterized by abnormal tracts between the perianal skin and the anal canal, presents challenges in treatment because of its diversity and complexity. This study investigates the use of non-thermal plasma as a postsurgical therapy for anal fistula, aiming to promote healing and tissue regeneration. A specialized plasma reactor was designed to apply non-thermal plasma within the anorectal cavity practically. Non-thermal plasma treatment was administered to 20 patients including 10 undergoing fistulectomies and 10 undergoing fistulotomies. The average duration of non-thermal plasma application in the operating room was shorter for fistulotomies. The pain reported the day after surgery was similar in both groups. Improvements in the number of evacuations starting from the day after surgery, as well as the assessment of stool quality using the Bristol scale, indicated satisfactory intestinal recovery. Fistulotomy patients exhibited faster wound healing times. These findings underscore the efficacy of non-thermal plasma as a postoperative therapy for anal fistula, enhancing healing and recovery outcomes without increasing complication risks.
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The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long-term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura-2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time-dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long-term administration of rapamycin to kidney transplant patients evokes alteration in platelet function.
Assuntos
Plaquetas/patologia , Cálcio/metabolismo , Homeostase/efeitos dos fármacos , Transplante de Rim , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Plaquetas/efeitos dos fármacos , Demografia , Ativação Enzimática/efeitos dos fármacos , Everolimo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fatores de TempoRESUMO
Recurrent aphthous stomatitis (RAS) is a common disease in the oral cavity characterized by recurrent ulcers (RU). Usually, these cause acute pain without definitive treatment. The present study determines the efficacy of non-thermal plasma (NTP) for treating RU. NTP is applied to the patient's RU using a radiofrequency generator connected to a point reactor. The power density applied to the ulcer is 0.50 W/cm2, less than 4 W/cm2, which is the maximum value without biological risk. Each patient received two treatments of three minutes each and spaced 60 min apart at a distance of 5 mm from the RU. From a sample of 30 ulcers in patients treated for RU with an average age of 37 years, they stated that the pain decreased considerably and without the need for ingestion of analgesics and antibiotics. Regeneration took place in an average of three days. The NTP proved to be an excellent therapeutic alternative for the treatment of RU since it has a rapid effect of reducing pain and inflammation, as well as adequate tissue regeneration.
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Non-thermal plasmas (NTPs), known as cold atmospheric plasmas (CAPs), hold great potential for diverse medical applications, including dentistry. However, traditional linear and rigid dielectric barrier discharge reactors used for NTP generation encounter limitations in accessing oral cavities and root canals. To address this issue, we have developed an innovative NTP reactor featuring an angled end for improved accessibility. The central copper electrode, with a 0.59 mm diameter and adjustable length for desired angulation, is coated with zircon powder (ZrSiO4) to ensure stable NTP generation. This central electrode is housed within a stainless steel tube (3 mm internal diameter, 8 mm external diameter, and 100 mm length) with a 27° angle at one end, making it ergonomically suitable for oral applications. NTP generation involves polarizing the reactor electrodes with 13.56 MHz radio frequency signals, using helium gas as a working medium. We introduce plasma-treated water (PTW) as an adjunctive therapy to enhance biofilm eradication within root canals. A synergistic approach combining NTP and PTW is employed and compared to the gold standard (sodium hypochlorite, NaOCl), effectively neutralizing Enterococcus faecalis bacteria, even in scenarios involving biofilms. Moreover, applying NTP in both gaseous and liquid environments successfully achieves bacterial inactivation at varying treatment durations, demonstrating the device's suitability for medical use in treating root canal biofilms. The proposed NTP reactor, characterized by its innovative design, offers a practical and specific approach to plasma treatment in dental applications. It holds promise in combatting bacterial infections in root canals and oral cavities.
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The permeation of dioxin-like pollutants, namely, chlorinated dibenzodioxins and dibenzofurans, through lipid membranes has been simulated using classic molecular dynamics (CMD) combined with the umbrella sampling approach. The most toxic forms of chlorinated dibenzodioxin and dibenzofuran, 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), and a dioleyl-phosphatidylcholine (DOPC) lipid membrane of 50 Å wide have been chosen for our study. The free energy profile shows the penetration process is largely favoured thermodynamically (ΔG ≈ -12 kcal/mol), with a progressively decrease of the free energy until reaching the energy minima at distances of 8 Å and 9.5 Å from the centre of the membrane for, respectively, TCDD and TCDF. At the centre of the membrane, both molecules display subtle local maxima with free energy differences of 0.5 and 1 kcal/mol with respect to the energy minima for TCDD and TCDF, respectively. Furthermore, the intermolecular interactions between the molecules and the lipid membrane have been characterized at the minima and the local maxima using hybrid quantum mechanics/molecular mechanics energy decomposition analysis (QM/MM-EDA). Total interaction energies of -17.5 and -16.5 kcal/mol have been found at the energy minima for TCDD and TCDF, respectively. In both cases, the dispersion forces govern the molecule-membrane interactions, no significant changes have been found at the local maxima, in agreement with the classical free energy profile. The small differences found in the results obtained for TCDD and TCDF point out that the adsorption and diffusion processes through the cell membrane are not related to the different toxicity shown by these pollutants.
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OBJECTIVE: an innovative non-thermal plasma (NTP) system constituted by a radiofrequency (RF) power generator directly coupled to a treatment probe is described and characterized. This system is intended to be applied as a medical device for therapeutic treatments. METHODS: electrical characterization of the radiofrequency power generator supplying the treatment probe was performed. Meanwhile, generated NTP was optically analyzed. Obtained data were studied to establish the safety profile of plasma application on heat sensitive matter. RESULTS: the NTP system was validated through bacterial deactivation trials, as well as, of being capable of deactivating carcinogenic cells. Besides promoting and accelerating wound closure in vivo performed in mice, demonstrating faster healing than that done with conventional treatments. CONCLUSION: the NTP system's characterization is an essential stage to determine the adequate application of the generated plasma over organic media. The therapeutic benefits of the NTP system were proved by the development of in vivo experiences involving laboratory mice. SIGNIFICANCE: the generated NTP interacts with surrounding air particles producing reactive oxygen and nitrogen species, which, exhibit bactericidal and antiseptic effects due to their strong biochemical reactivity; functioning like critical mediators in animal physiology and promoting wound healing processes. These properties make the NTP system a feasible technology intended for therapeutic treatments.
Assuntos
Gases em Plasma , Animais , CamundongosRESUMO
BACKGROUND: Focused parathyroidectomy (FP) is offered to 60% to 70% of patients presenting to our unit with primary hyperparathyroidism (PHPT). A recent report identified bilateral internal jugular venous sampling (BIJVS) as a useful tool for localization of parathyroid adenomas in patients with scan-negative PHPT. The purpose of this study was to evaluate the utility of this approach in a clinical setting. METHODS: A prospective case-control trial was undertaken. Bilateral internal jugular venous blood samples were obtained. Patients were stratified into three groups: Group A consisted of patients with a negative sestamibi scan undergoing bilateral exploration; group B consisted of patients undergoing FP following a positive sestamibi scan; and group C patients were a control group undergoing total thyroidectomy. RESULTS: In group A, 17 of 30 patients (56%) had lateralization of the parathyroid hormone (PTH) levels, with 11 correctly lateralizing to the side of the adenoma, 5 lateralizing despite bilateral disease, and 1 lateralizing to the contralateral side. Of the remaining 13 patients in whom there was no lateralization, 3 had bilateral multigland disease, and 10 had a single parathyroid adenoma. In group B, 17 of 30 patients (56%) also had lateralization of PTH levels, with 15 lateralizing to the side of the adenoma and 2 to the contralateral side. Lateralization failed in the remaining 13 patients, although in all of these patients the calcium and PTH levels normalized postoperatively. The control group of patients without parathyroid disease (group C) demonstrated lateralization of PTH levels in 23 of 30 patients (76%). CONCLUSIONS: In our hands, BIJVS for PTH determination was not a useful adjunctive test facilitating FP. We continue to offer all patients with PHPT and a negative sestamibi scan a standard bilateral neck exploration.
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Hiperparatireoidismo Primário/sangue , Veias Jugulares , Hormônio Paratireóideo/sangue , Adenoma/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Cintilografia , Sensibilidade e EspecificidadeRESUMO
We describe a 31-year-old woman who had ingested minocycline for 18 months prior to presenting with hyperthyroidism and a palpable thyroid nodule. There was no evidence of Graves' disease or autonomous nodule on thyroid scintigraphy, and a clinical diagnosis of thyroiditis was made. Fine-needle aspiration biopsy of the palpable lesion suggested papillary carcinoma, and the patient underwent a total thyroidectomy. Intraoperatively, the thyroid gland was found to have a striking black discoloration. Subsequent histological examination revealed the accumulation of pigment globules within the apical cytoplasm of the follicular cells, and associated findings of a drug-induced thyroiditis. The tumor nodule showed features of infarction and was felt to represent a necrotic papillary microcarcinoma. We postulate that in addition to causing black thyroid pigmentation, chronic minocycline use in our patient resulted in thyroiditis and subsequent hyperthyroidism. The papillary microcarcinoma was probably a coincidental finding.
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Antibacterianos/efeitos adversos , Carcinoma Papilar/diagnóstico , Hipertireoidismo/induzido quimicamente , Minociclina/efeitos adversos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidite/induzido quimicamente , Acne Vulgar/tratamento farmacológico , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Feminino , Humanos , Hipertireoidismo/diagnóstico , Achados Incidentais , Minociclina/farmacologia , Minociclina/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Tireoidite/diagnósticoRESUMO
Introducción: El leiomiosarcoma de ovario, es una neoplasia extremadamente rara, forma parte del subgrupo de tumores de músculo liso que constituye menos del 1% en cuanto a tumores de ovario; dentro del mismo se encuentran clasificados el carcinosarcoma, angiosarcoma, fibrosarcoma y leiomiosarcoma, de acuerdo con la literatura revisada se han reportado 63 casos de leiomiosarcoma hasta la actualidad. Caso clínico: Presentamos el caso de una paciente mujer de 53 años; ingresó al área de emergencia por dolor abdominal de gran intensidad, acompañado de distensión abdominal y ortopnea; a la exploración física se palpó una masa poco móvil. La tomografía evidenció la presencia de una masa abdomino-pélvica que se extendió entre el asa intestinal y la raíz del mesenterio; comprimía vejiga, útero y ovarios. Se le realizó una histerectomía, con salpingo ooforectomía derecha, ooforectomía izquierda por medio de laparotomía exploratoria. Los estudios histopatológicos determinaron el diagnóstico de leiomiosarcoma. Fue tratado con cirugía y quimioterapia adyuvante.
Introduction: Ovarian leiomyosarcomas is an extremely rare neoplasm and are part of the subgroup of smooth muscle tumors that constitutes less than 1% in terms of ovarian tumors; within it are classified: carcinosarcoma, angiosarcoma, fibrosarcoma, and leiomyosarcoma, according to the reviewed literature, 63 cases of leiomyosarcoma have been reported to date. Clinical Case: We present the case of a 53-year-old female patient; she was admitted to the emergency area due to severe abdominal pain, accompanied by abdominal distension and orthopnea; Physical examination revealed a large, slightly mobile mass. The tomography showed the presence of an abdominopelvic mass that extended between the intestinal loop and the root of the mesentery; compressed bladder, uterus, and ovaries. She underwent exeresis hysterectomy with right salpingo-oophorectomy and left oophorectomy through exploratory laparotomy. Histopathological studies yielded results of a malignant neoplasm compatible with leiomyosarcoma. She was treated with surgery and adjuvant chemotherapy.
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Humanos , Feminino , Adulto , Neoplasias Ovarianas , Leiomiossarcoma , Ovário , Relatos de CasosRESUMO
BACKGROUND: Studies on allergic rhinitis prevalence have found significant variations in their results, even in closely-living populations. OBJECTIVE: To determine and compare the prevalence of allergic rhinitis and its symptoms in schoolchildren from Cuernavaca, Morelos, Mexico. METHODS: Cross-sectional, descriptive study on the prevalence of allergic rhinitis diagnosis and symptoms, where the "Diagnostic questionnaire for epidemiological studies" was used between June and December 2015 in pre-school and primary and secondary school population, after authorization was granted by parents and school authorities. RESULTS: In 7866 surveys in a population aged between 3 and 15 years, 939 cases of allergic rhinitis (11.94%) were identified, with 53% belonging to the female gender. The symptom with the highest prevalence was cold-induced nasal congestion (56.8%), followed by rhinitis accompanied by ocular symptoms (35.8%) and recurrent flu-like symptoms (20), which was the most common symptom in allergic rhinitis (100%). CONCLUSION: A significant variation was observed in the prevalence of symptoms, notably higher than that of questionnaire-obtained allergic rhinitis diagnosis (11.94%), which suggests that the independent prevalence of symptoms is not a good parameter to detect the prevalence of allergic rhinitis.
Antecedentes: En los estudios de prevalencia de rinitis alérgica se han encontrado amplias variaciones en sus resultados, incluso en poblaciones cercanas. Objetivo: Determinar y comparar la prevalencia de la rinitis alérgica y sus síntomas en escolares de Cuernavaca, Morelos, México. Métodos: Estudio transversal descriptivo de la prevalencia del diagnóstico de rinitis alérgica y de sus síntomas, en el que se empleó el "Cuestionario diagnóstico para estudios epidemiológicos", entre junio y diciembre de 2015, en población preescolar, escolar primaria y secundaria, previa autorización de padres y autoridades escolares. Resultados: En 7866 encuestas en población de 3 a 15 años de edad se identificaron 939 casos de rinitis alérgica (11.94 %), 53 % del sexo femenino. El síntoma con mayor prevalencia correspondió a constipación por frío (56.8 %), seguido por rinitis acompañada de síntomas oculares (35.8 %), cuadros catarrales recurrentes (20 %); el síntoma más frecuente fue la rinitis alérgica (100 %). Conclusiones: Se apreció amplia variación en la prevalencia de los síntomas, notablemente más alta que la del diagnóstico de rinitis alérgica obtenida por el cuestionario (11.94 %), lo que sugiere que la prevalencia independiente de los síntomas no es buen parámetro para detectar la prevalencia de la rinitis alérgica.
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Rinite Alérgica/epidemiologia , Adolescente , Criança , Pré-Escolar , Conjuntivite Alérgica/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , México/epidemiologia , Prevalência , Inquéritos e Questionários , Avaliação de SintomasRESUMO
A cold plasma produced with helium gas was applied to two second-degree burns produced with boiling oil. These burns were located on a thigh and a shin of a 59-years-old male person. After the first treatment as benefit the patient neither presented itching nor pain and, after the second treatment, the patient presented new tissue. This result opens the possibilities of the application of a cold plasma source to health burns.
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In this work we have determined the role of the 26S proteasome in the regulation of the content of progesterone receptors (PR-A and PR-B), estrogen receptors (ER-alpha and ER-beta), the coactivator SRC-1 and the corepressor SMRT in the rat brain during the estrous cycle. The 26S proteasome inhibitor MG132 was injected once into the lateral ventricle on proestrous day; and 24h later, on estrous day we evaluated the content of PR and ER isoforms, SRC-1 and SMRT in the hypothalamus, the preoptic area and the hippocampus by Western blot. A significant increase in the content of both PR isoforms, ER-beta and SRC-1 was observed after the administration of MG132 in the three studied cerebral regions. SMRT content was increased in the hypothalamus and the preoptic area and a significant increase in ER-alpha content was only observed in the preoptic area. These results suggest that essential proteins that participate in progesterone and estrogen actions in the brain should be regulated by the 26S proteasome in a tissue-specific manner in physiological conditions.
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Encéfalo/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Ciclo Estral/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Progesterona/metabolismo , Complexo de Endopeptidases do Proteassoma/farmacologia , Receptores de Estrogênio/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Animais , Western Blotting/métodos , Encéfalo/metabolismo , Ciclo Estral/fisiologia , Feminino , Histona Acetiltransferases , Correpressor 2 de Receptor Nuclear , Coativador 1 de Receptor Nuclear , Ratos , Ratos WistarRESUMO
BACKGROUND: A relatively high proportion of deaths in dialysis patients occur suddenly and unexpectedly. The incidence of sudden cardiac death (SCD) in non-dialysis advanced chronic kidney disease (CKD) stages has been less well investigated. OBJECTIVE: This study aims to determine the incidence and predictors of SCD in a cohort of 1078 patients with CKD not yet on dialysis. METHODS: Prospective observational cohort study, which included patients with advanced CKD not yet on dialysis (stage 4-5). The association between baseline variables and SCD was assessed using Cox and competing-risk (Fine and Grey) regression models. Demographic, clinical information, medication use, and baseline biochemical parameters of potential interest were included as covariates. RESULTS: During the study period (median follow-up time 12 months), 210 patients died (19%), and SCD occurred in 34 cases (16% of total deaths). All-cause mortality and SCD incidence rates were 113 (95% CI: 99-128), and 18 (95% CI: 13-26) events per 1000 patients/year, respectively. By Cox regression analysis, covariates significantly associated with SCD were: Age, comorbidity index, and treatment with antiplatelet drugs. This latter covariate showed a beneficial effect over the development of SCD. By competing-risk regression, in which the competing event was non-sudden death from any cause, only age and comorbidity index remained significantly associated with SCD. CONCLUSIONS: SCD is relatively common in non-dialysis advanced CKD patients. SCD was closely related to age and comorbidity, and some indirect data from this study suggest that unrecognised or undertreated cardiovascular disease may predispose to a higher risk of SCD.
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Morte Súbita Cardíaca/epidemiologia , Falência Renal Crônica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Comorbidade , Morte Súbita Cardíaca/etiologia , Feminino , Hematínicos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
RESUMEN: El hepatoblastoma (HB), es una neoplasia maligna, que se origina en el hígado. La supervivencia (SV) depende de la extensión de avance de la enfermedad. El objetivo de este estudio fue determinar diferencias en la SV actuarial global (SVAG) y libre de enfermedad (SVLE) en pacientes con HB, según la extensión de su enfermedad. Serie de casos con seguimiento. Se incluyeron pacientes de entre 4 y 160 meses de edad tratados en un centro oncológico de Los Andes ecuatorianos (2000-2019). Las variables resultado fueron: lóbulo afectado, metástasis pulmonar, infiltración vascular, estadio PRETEXT, riesgo, histología, niveles de alfafetoproteína (AFP), remisión completa (RC), SVAG y SVLE. Se utilizó estadística descriptiva y analítica (Chi2, exacto de Fisher y corrección por continuidad). Se realizaron análisis de SV con curvas de Kaplan Meier y log-rank. Fueron estudiados 28 pacientes (53,6 % hombres), con una mediana de edad de 40 meses. Se verificaron metástasis pulmonares e infiltración vascular en el 25,0 % y 35,7 % de los casos respectivamente. La histología, estadio clínico y riesgo alto fueron mayoritariamente tipo epitelial (42,8 %), PRETEXT II (50,0 %) y riesgo alto (67,8 %) respectivamente. La media de AFP al diagnóstico fue 1055712ng/ml y 9 pacientes alcanzaron RC. La SVAG y SVLE general a 19 años fue 33,1 % y 26,0 % respectivamente. Según su extensión, la SVAG y la SVLE para los pacientes de riesgo estándar y alto fueron 50,0 % y 25,4 % (p=0,148); y 50,0 % y 14,7 % (p=0,037) respectivamente. La SVAG y SVLE verificadas son menores a las reportadas en otros estudios. La SVLE según su extensión, presentó diferencia significativa, sin embargo, este resultado debe ser tomado con cautela debido al número pequeño de pacientes.
SUMMARY: Hepatoblastoma (HB), is a malignant neoplasm, which originates in the liver. Survival (SV) depends on the extent of disease progression. The objective of this study was to determine differences in overall SV (OS) and disease-free (DFS) in patients with HB, according to the extent of their disease. Case series with follow-up. Patients between 4 and 160 months of age treated at an oncology center in the Ecuadorian Andes (2000-2019) were included. The result variables were affected lobe, lung metastasis, vascular infiltration, PRETEXT stage, risk, histology, alpha-fetoprotein levels (AFP), complete remission (RC), OS and DFS. Descriptive and analytical statistics (Chi2, Fisher's exact and continuity correction) were used. SV analyzes were performed with Kaplan Meier and log-rank curves. In this analysis 28 patients (53.6 % men), with a median age of 40 months, were studied. Lung metastases and vascular infiltration were verified in 25.0 % and 35.7 % of the cases, respectively. Histology, clinical stage, and high risk were mainly epithelial type (42.8 %), PRETEXT II (50.0 %), and high risk (67.8 %), respectively. The mean AFP at diagnosis was 1055712 ng / ml and 9 patients achieved CR. OS and DFS at 19 years were 33.1 % and 26.0 % respectively. According to their extension, the OS and DFS for standard and high risk patients were 50.0 % and 25.4 % (p = 0.148); and 50.0 % and 14.7 % (p = 0.037) respectively. The verified OS and DFS are lower than those reported in other studies. DFS according to its extension, presented a significant difference, however, this result should be considered with caution due to the small number of patients.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Hepatoblastoma/cirurgia , Hepatoblastoma/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Análise de Sobrevida , Seguimentos , Resultado do Tratamento , Quimioterapia Adjuvante , Medição de Risco , EquadorRESUMO
BACKGROUND: Asthma is a chronic disease that has increased over the past 2 decades. OBJECTIVE: To determine the prevalence of asthma and its symptoms in the city of Cuernavaca, Morelos, Mexico. METHODS: A descriptive study of prevalence in public schools of the city of Cuernavaca, Morelos, at the preschool, elementary, and high school levels using the "Asthma diagnosis for epidemiological studies questionnaire." RESULTS: 7947 surveys were obtained from students ages 3 to 15 years, funding a prevalence of asthma of 11.9%, 49% in boys and 51% in girls. As for the symptoms of asthma, the highest prevalence was cough that increases with cold weather (63%), however, in asthma patients this symptom only occurred in 17%; chest tightness had the lowest prevalence of symptoms (10%); however, in asthma patients it was 49%. CONCLUSIONS: The asthma diagnosis for epidemiological studies questionnaire found an average asthma prevalence of 11.9% in preschool, elementary, and high school students, slightly below that diagnosed in other cities in central Mexico. The prevalence of asthma symptoms was higher than the diagnosis of asthma.
Antecedentes: El asma es una enfermedad crónica que se ha incrementado en las 2 últimas décadas. Objetivo: Determinar la prevalencia de asma y sus síntomas en la ciudad de Cuernavaca, Morelos, México. Métodos: Estudio descriptivo de prevalencia en escuelas oficiales de la ciudad de Cuernavaca, Morelos, de nivel preescolar, primaria y secundaria, mediante el "Cuestionario diagnóstico de asma para estudios epidemiológicos". Resultados: Se obtuvieron 7947 encuestas en escolares de 3 a 15 años, encontrándose una prevalencia de asma de 11.9%, 49% en niños y 51 % en niñas. En cuanto a los síntomas de asma, la mayor prevalencia la obtuvo la tos que aumenta con el frío (63%), sin embargo, en los pacientes con asma este síntoma solo se presentó en 17%; la opresión torácica tuvo la prevalencia más baja entre los síntomas (10%), sin embargo, en pacientes con asma fue de 49%. Conclusiones: Con el cuestionario diagnóstico de asma para estudios epidemiológicos se encontró una prevalencia promedio de asma de 11.9% en preescolares, escolares y alumnos de secundaria, discretamente inferior a la diagnosticada en otras ciudades del centro de México. La prevalencia de los síntomas de asma resultó más elevada que la del diagnóstico de asma.
Assuntos
Asma/epidemiologia , Avaliação de Sintomas , Adolescente , Asma/diagnóstico , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , México/epidemiologia , Prevalência , Inquéritos e QuestionáriosRESUMO
La linfangiomatosis es una patología benigna, de etiología desconocida, que afecta especialmente a población pediátrica, caracterizándose por desarrollo de masas subcutáneas que involucran uno o más órganos. Cuando se asocia con coagulopatía y derrames quilosos, recibe el nombre de linfangiomatosis kaposiforme (LK), cuya evidencia disponible es escasa. El objetivo de este manuscrito es reportar un caso de LK pediátrico atendido en el Instituto del Cáncer SOLCA, Cuenca, Ecuador. Paciente femenina de 1 año 7 meses, con hernia inguinal bilaterales y alteración de los tiempos de coagulación. En los estudios de imagen se evidenció una masa mediastínica asociada a presencia de líquido en espacio pleural y cavidad abdomino-pélvica. Además, se evidenció la existencia de múltiples imágenes hipogénicas en el bazo. Se practicó timectomía mínima, toma de biopsia de linfonodos mediastínicos para establecer el diagnóstico, y se instaló un dren en el tórax para tratar el derrame pleural antes señalado. Se descartaron patologías similares (linfomas, lupus, inmunológicas, etc.). Dado el continúo deterioro respiratorio, coagulopatía, lesiones hipogénicas esplénicas y drenaje abundante del quilotórax por el tubo torácico, se planteó el diagnóstico de LK. Se inició apoyo nutricional vía parenteral (sin lípidos); se indicó vincristina, y se realizó una pleurodesis con bleomicina sin buena respuesta. La paciente falleció a los 16 días de su ingreso. Se trata de un caso de mal pronóstico, con evolución rápidamente progresiva hacia un desenlace fatal.
Lymphangiomatosis is a benign pathology, of unknown etiology. Affects especially to pediatric population and is characterized by development of subcutaneous masses that involve one or more organs. When it presents with coagulopathy and chylous effusions, it is called kaposiform lymphangiomatosis (KL). The available evidence of KL is scarce. The objective of this manuscript was to report a case of pediatric KL treated at SOLCA Cancer Institute, Cuenca, Ecuador. Female patient of 1 year and 7 months age. She had a bilateral inguinal hernia and altered coagulation times. Imaging studies revealed a mediastinal mass associated with fluid in the pleural space and in the abdominalpelvic cavity. Furthermore, the existence of multiple hypogenic images in the spleen was evidenced. Minimal thymectomy, biopsy of mediastinal lymph nodes was performed to establish the diagnosis, and a drain was installed in the chest to treat the aforementioned pleural effusion. Other pathologies like lymphomas, lupus, etc. were ruled out. Given the continuous respiratory deterioration, coagulopathy, splenic hypogenic lesions and abundant drainage of the chylothorax through the chest tube, the diagnosis of KL was raised. Parenteral nutrition (lipid-free) was started; Vincristine was indicated, and a pleurodesis with bleomycin was performed without a good response. The patient died 16 days after her admission. It is a case of very bad prognosis, with a rapidly progressive evolution towards a fatal outcome.