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The unique phase in a crystal of triphenylsilanol (Ph3SiOH) is reported. It is observed that after the crystal is flash-cooled from room temperature to 100â K, a new stable ordered phase II occurs with an increase in the unit-cell parameters compared to the earlier reported phase I. The new phase II occurs upon fast cooling while on slow cooling the disordered phase I is present. Gradual heating from 100â K (phase II) causes the crystal to return to the original phase I at about 150â K. The crystal undergoes the observed transformation in a reversible manner in many consecutive flash cooling/heating cycles without cracking.
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Cough during therapeutic thoracentesis (TT) is considered an adverse effect. The study was aimed to evaluate the relationship between cough during TT and pleural pressure (Ppl) changes (∆P). Instantaneous Ppl was measured after withdrawal of predetermined volumes of pleural fluid. Fluid withdrawal (FW) and Ppl measurement (PplM) periods were analyzed separately using the two sample Kolmogorov-Smirnov test and the nonparametric skew to assess differences between ∆P distributions in periods with and without cough. The study involved 59 patients, median age 66 years, median withdrawn fluid volume 1800 mL (1330 ÷ 2400 mL). In total, 1265 cough episodes were recorded in 52 patients, in 24% of FW and 19% of PplM periods, respectively. Cough was associated with significant changes in ∆P distribution (p < 0.001), decreasing the left tail of ∆P distribution for FW periods (the skew = - 0.033 vs. - 0.182) and increasing the right tail for PplM periods (the skew = 0.182 vs. 0.088). Although cough was more frequent in 46 patients with normal pleural elastance (p < 0.0001), it was associated with significantly higher ∆P in patients with elevated elastance (median Ppl increase 2.9 vs. 0.2 cmH2O, respectively). Cough during TT is associated with small but beneficial trend in Ppl changes, particularly in patients with elevated pleural elastance, and should not be considered solely as an adverse event.
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Derrame Pleural , Toracocentesis , Anciano , Tos/etiología , Humanos , Paracentesis , Pleura , Derrame Pleural/etiologíaRESUMEN
INTRODUCTION: Therapeutic thoracentesis is highly effective in providing symptomatic improvement in patients with large volume pleural effusion (PE). However, some physiological effects of pleural fluid (PF) withdrawal are still not fully elucidated. OBJECTIVES: The study aimed to evaluate alterations in the breathing pattern, pulmonary function, and arterial blood gases (ABG) in relation to both withdrawn PF volume and pleural pressure (Ppl) changes in patients undergoing therapeutic thoracentesis. PATIENTS AND METHODS: This prospective, observational, crosssectional study included 37 patients with large volume PE. Respiratory rate (RR), dyspnea, pulmonary function, and ABG were assessed before the thoracentesis, at the termination of the PF withdrawal and 1, 3, and 24 hours after the procedure. The volume of PF drained, Ppl, and tidal volume (TV) were monitored during the thoracentesis. RESULTS: Thoracentesis resulted in a transient but significant increase in RR directly after the procedure, and a transient decrease, followed by subsequent increase in TV. There was a significant and constant increase in forced vital capacity up to 24 hours after thoracentesis (P = 0.001). Oxygen partial pressure (PaO2) significantly improved directly after PF withdrawal (P = 0.01) and returned to baseline values after 24 hours. Thoracentesis was invariably associated with a significant increase in the amplitude of Ppl (Ppl_ampl) changes during the respiratory cycle (P <0.001). CONCLUSIONS: Therapeutic thoracentesis results in a modest improvement in pulmonary function, tran-sient increase in PaO2 and increase in Ppl_ampl. The improvement in pulmonary function and ABG is closely related to the volume of PF drained and pleural elastance. The increase in Ppl_ampl probably represents a more efficient work of the respiratory muscles.
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Derrame Pleural , Toracocentesis , Estudios Transversales , Disnea/terapia , Gases , Humanos , Pulmón , Oxígeno , Estudios Prospectivos , Frecuencia RespiratoriaRESUMEN
Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite-methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients' life. Therefore, novel targeted therapies based on the malignant cells' common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose-methotrexate conjugate (Glu-MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu-MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu-MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients' outcomes.
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Antimetabolitos Antineoplásicos/farmacología , Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Glucosa/farmacología , Proteínas Facilitadoras del Transporte de la Glucosa/antagonistas & inhibidores , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Humanos , Inmunoconjugados/farmacología , Linfoma no Hodgkin/genética , Linfoma no Hodgkin/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose-methotrexate conjugate (GLU-MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter-1 (GLUT1). GLU-MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU-MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU-MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU-MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.
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Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos/química , Glucosa/química , Metotrexato/administración & dosificación , Animales , Antimetabolitos Antineoplásicos/farmacocinética , Neoplasias de la Mama/patología , Línea Celular Tumoral/trasplante , Modelos Animales de Enfermedad , Liberación de Fármacos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Ácido Fólico/biosíntesis , Transportador de Glucosa de Tipo 1/antagonistas & inhibidores , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Inyecciones Intravenosas , Metotrexato/farmacocinética , RatonesRESUMEN
Tick-borne encephalitis virus (TBEV) transmitted by ticks is a pathogen of great medical importance. As still no effective antiviral treatment is available, in the present study, a series of uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure was synthesized and evaluated for the antiviral activity against two strains of TBEV: a highly virulent Hypr strain and less virulent Neudoerfl strain, using standardized previously in vitro assays. Our data have shown that four compounds from the series (18-21) possess strong activity against both TBEV strains. The half maximal inhibitory concentration (IC50) values of compounds 18-21 were between 15.1 and 3.7 µM depending on the virus strain, which along with low cytotoxicity resulted in high values of the selectivity index (SI). The obtained results suggest that these compounds may be promising candidates for further development of new therapies against flaviviruses.
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Nanoparticles based on amphiphilic copolymers with tunable physicochemical properties can be used to encapsulate delicate pharmaceutics while at the same time improving their solubility, stability, pharmacokinetic properties, reducing immune surveillance, or achieving tumor-targeting ability. Those nanocarriers based on biodegradable aliphatic polycarbonates are a particularly promising platform for drug delivery due to flexibility in the design and synthesis of appropriate monomers and copolymers. Current studies in this field focus on the design and the synthesis of new effective carriers of hydrophobic drugs and their release in a controlled manner by exogenous or endogenous factors in tumor-specific regions. Reactive groups present in aliphatic carbonate copolymers, undergo a reaction under the action of a stimulus: e.g., acidic hydrolysis, oxidation, reduction, etc. leading to changes in the morphology of nanoparticles. This allows the release of the drug in a highly controlled manner and induces a desired therapeutic outcome without damaging healthy tissues. The presented review summarizes the current advances in chemistry and methods for designing stimuli-responsive nanocarriers based on aliphatic polycarbonates for controlled drug delivery.
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The oxygen and nutrient-deprived tumor microenvironment is considered a key mechanism responsible for cancer resistance to chemotherapy. Methotrexate (MTX) is a widely incorporated chemotherapeutic agent employed in the treatment of several malignancies. However, drug resistance and systemic toxicity limit the curative effect in most cases. The present work aimed to design, synthesize, and biologically evaluate a novel glucose-methotrexate conjugate (Glu-MTX). Our study showed that Glu-MTX exerts an increased cytotoxic effect on cancer cells in comparison to MTX in hypoxia (1% O2) and glucose starvation conditions. Furthermore, Glu-MTX was found to inhibit the proliferation and migration of cancer cells more effectively than MTX does. Our results demonstrate that the conjugation of MTX to glucose led to an increase in potency against malignant cells under oxygen and nutrient stress. The observations shed light on a potential therapeutic approach to overcome chemoresistance in cancer.
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Pentacyclic lupane-type triterpenoids, such as betulin and its synthetic derivatives, display a broad spectrum of biological activity. However, one of the major drawbacks of these compounds as potential therapeutic agents is their high hydrophobicity and low bioavailability. On the other hand, the presence of easily transformable functional groups in the parent structure makes betulin have a high synthetic potential and the ability to form different derivatives. In this context, research on the synthesis of new betulin derivatives as conjugates of naturally occurring triterpenoid with a monosaccharide via a linker containing a heteroaromatic 1,2,3-triazole ring was presented. It has been shown that copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction (CuAAC) provides an easy and effective way to synthesize new molecular hybrids based on natural products. The chemical structures of the obtained betulin glycoconjugates were confirmed by spectroscopic analysis. Cytotoxicity of the obtained compounds was evaluated on a human breast adenocarcinoma cell line (MCF-7) and colorectal carcinoma cell line (HCT 116). The obtained results show that despite the fact that the obtained betulin glycoconjugates do not show interesting antitumor activity, the idea of adding a sugar unit to the betulin backbone may, after some modifications, turn out to be correct and allow for the targeted transport of betulin glycoconjugates into the tumor cells.
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Alquinos/farmacología , Antineoplásicos/farmacología , Azidas/farmacología , Cobre/química , Glicoconjugados/farmacología , Triterpenos/farmacología , Alquinos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Azidas/química , Catálisis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Reacción de Cicloadición , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glicoconjugados/síntesis química , Glicoconjugados/química , Humanos , Estructura Molecular , Relación Estructura-Actividad , Triterpenos/síntesis química , Triterpenos/químicaRESUMEN
One of the main factors limiting the effectiveness of many drugs is the difficulty of their delivery to their target site in the cell and achieving the desired therapeutic dose. Moreover, the accumulation of the drug in healthy tissue can lead to serious side effects. The way to improve the selectivity of a drug to the cancer cells seems to be its conjugation with a sugar molecule, which should facilitate its selective transport through GLUT transporters (glucose transporters), whose overexpression is seen in some types of cancer. This was the idea behind the synthesis of 8-hydroxyquinoline (8-HQ) derivative glycoconjugates, for which 1-thiosugar derivatives were used as sugar moiety donors. It was expected that the introduction of a sulfur atom instead of an oxygen atom into the anomeric position of the sugar would increase the stability of the obtained glycoconjugates against untimely hydrolytic cleavage. The anticancer activity of new compounds was determined based on the results of the MTT cytotoxicity tests. Because of the assumption that the activity of this type of compounds was based on metal ion chelation, the effect of the addition of copper ions on cell proliferation was tested for some of them. It turned out that cancer cells treated with glycoconjugates in the presence of Cu2+ had a much slower growth rate compared to cells treated with free glycoconjugates in the absence of copper. The highest cytotoxic activity of the compounds was observed against the MCF-7 cell line.
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Antineoplásicos/farmacología , Glicoconjugados/síntesis química , Oxiquinolina/farmacología , Azufre/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Cobre/química , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Iones , Células MCF-7 , Relación Estructura-Actividad , AzúcaresRESUMEN
Pleural manometry enables the assessment of physiological abnormalities of lung mechanics associated with pleural effusion. Applying pleural manometry, we found small pleural pressure curve oscillations resembling the pulse tracing line. The aim of our study was to characterize the oscillations of pleural pressure curve (termed here as the pleural pressure pulse, PPP) and to establish their origin and potential significance. This was an observational cross-sectional study in adult patients with pleural effusion who underwent thoracentesis with pleural manometry. The pleural pressure curves recorded prior to and during fluid withdrawal were analyzed. The presence of PPP was assessed in relation to the withdrawn pleural fluid volume, lung expandability, vital and echocardiographic parameters, and pulmonary function testing. A dedicated device was developed to compare the PPP to the pulse rate. Fifty-four patients (32 women) median age 66.5 (IQR 58.5-78.7) years were included. Well visible and poorly visible pressure waves were detected in 48% and 35% of the patients, respectively. The frequency of PPP was fully concordant with the pulse rate and the peaks of the oscillations reflected the period of heart diastole. PPP was more visible in patients with a slower respiratory rate (p = 0.008), a larger amount of pleural effusion, and was associated with a better heart systolic function assessed by echocardiography (p < 0.05). This study describes a PPP, a new pleural phenomenon related to the cyclic changes in the heart chambers volume. Although the importance of PPP remains largely unknown, we hypothesize that it could be related to lung atelectasis or lower lung and visceral pleura compliance.
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Biodegradable triblock copolymer poly(ethylene glycol)-b-polycarbonate-b-oligo([R]-3-hydroxybutyrate) was prepared via metal-free ring-opening polymerization of ketal protected six-membered cyclic carbonate followed by esterification with bacterial oligo([R]-3-hydroxybutyrate) (oPHB). Amphiphilic triblock copolymer self-organizes into micelles with a diameter of ~25 nm. Acid-triggered hydrolysis of ketal groups to two hydroxyl groups causes an increase in hydrophilicity of the hydrophobic micelle core, resulting in the micelles swell and drug release. oPHB was added as core-forming block to increase the stability of prepared micelles in all pH (7.4, 6.4, 5.5) studied. Doxorubicin and 8-hydroxyquinoline glucose- and galactose conjugates were loaded in the micelles. In vitro drug release profiles in PBS buffers with different pH showed that a small amount of loaded drug was released in PBS at pH 7.4, while the drug was released much faster at pH 5.5. MTT assay showed that the blank micelles were non-toxic to different cell lines, while glycoconjugates-loaded micelles, showed significantly increased ability to inhibit the proliferation of MCF-7 and HCT-116 cells compared to free glycoconjugates. The glycoconjugation of anti-cancer drugs and pH-responsive nanocarriers have separately shown great potential to increase the tumor-targeted drug delivery efficiency. The combination of drug glycoconjugation and the use of pH-responsive nanocarrier opens up new possibilities to develop novel strategies for efficient tumor therapy.
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Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Glicoconjugados/metabolismo , Micelas , Oxiquinolina/metabolismo , Efecto Warburg en Oncología/efectos de los fármacos , Implantes Absorbibles , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Glicoconjugados/administración & dosificación , Células HCT116 , Humanos , Concentración de Iones de Hidrógeno , Oxiquinolina/administración & dosificaciónRESUMEN
Despite the progress in the development of novel treatment modalities, a significant portion of patients with psoriasis remains undertreated relative to the severity of their disease. Recent evidence points to targeting the glucose transporter 1 and sugar metabolism as a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases. In this review, we discuss glycoconjugation, an approach that facilitates the pharmacokinetics of cytotoxic molecules and ensures their preferential influx through glucose transporters. We propose pathways of glycoconjugate synthesis to increase effectiveness, cellular selectivity, and tolerability of widely used antipsoriatic drugs. The presented approach exploiting the heightened glucose requirement of proliferating keratinocytes bears the potential to revolutionize the management of psoriasis. SIGNIFICANCE STATEMENT: Recent findings concerning the fundamental role of enhanced glucose metabolism and glucose transporter 1 overexpression in the pathogenesis of psoriasis brought to light approaches that proved successful in cancer treatment. Substantial advances in the emerging field of glycoconjugation highlight the rationale for the development of glucose-conjugated antipsoriatic drugs to increase their effectiveness, cellular selectivity, and tolerability. The presented approach offers a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases.
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Glicoconjugados/uso terapéutico , Psoriasis/tratamiento farmacológico , Desarrollo de Medicamentos , Glucosa/metabolismo , Transportador de Glucosa de Tipo 1/fisiología , Glicoconjugados/biosíntesis , Glicoconjugados/farmacocinética , Humanos , Psoriasis/metabolismo , Distribución TisularRESUMEN
Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of ß-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.
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Antineoplásicos/química , Antineoplásicos/farmacología , Glicoconjugados/farmacología , Oxiquinolina/análogos & derivados , Oxiquinolina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Galactosiltransferasas/antagonistas & inhibidores , Glicoconjugados/química , Células HCT116 , Humanos , Células MCF-7 , Metales/química , Metales/farmacología , Modelos Moleculares , Oxiquinolina/química , Relación Estructura-ActividadRESUMEN
8-Hydroxyquinoline scaffold is a privileged structure used in designing a new active agents with therapeutic potential. Its connections with the sugar unit is formed to improve the pharmacokinetic properties. The broad spectrum of activity of quinoline derivatives, especially glycoconjugates, is often associated with the ability to chelate metal ions or with the ability to intercalate into DNA. Simple and effective methods of synthesis glycoconjugates of 8-hydroxyquinoline and 8-hydroxyquinaldine derivatives, containing an O-glycosidic bond or a 1,2,3-triazole linker in their structure, have been developed. The obtained glycoconjugates were tested for their ability to inhibit ß-1,4-Galactosyltransferase, as well as inhibit cancer cell proliferation. It was found that used glycoconjugation strategy influenced both improvement of activity and improvement of the bioavailability of 8-HQ derivatives. Their activity depends on type of attached sugar, presence of protecting groups in sugar moiety and presence of a linker between sugar and quinolone aglycone.
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Antineoplásicos/síntesis química , Galactosiltransferasas/antagonistas & inhibidores , Glicoconjugados/química , Oxiquinolina/química , Animales , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Bovinos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Galactosiltransferasas/metabolismo , Glicoconjugados/metabolismo , Glicoconjugados/farmacología , Humanos , Concentración 50 Inhibidora , Leche/enzimología , Relación Estructura-ActividadRESUMEN
BACKGROUND: Due to numerous late complications after laparoscopic adjustable gastric banding (LAGB), leading to band removal, a significant decrease of its application has been observed. OBJECTIVES: The objective of this study was to present complications after LAGB in our own material. MATERIAL AND METHODS: The study included 152 obese patients who underwent LAGB between 2005 and 2012. The group of women consisted of 91 patients (60%) with the following preoperative parameters: average body mass index (BMI) 42 ±3.66 kg/m2 and average body mass 122 ±12.8 kg. The group of men included 61 patients (40%) with a preoperative average BMI 43 ±3.81 kg/m2 and average body mass 125 ±13.02 kg. The average age of women was 35.02 ±11.6 years and of men 36.18 ±10.5 years. RESULTS: Among 152 patients after LAGB due to morbid obesity, in 7 (4.6%) migration of the band to the stomach lumen was observed, in 4 port wound purulence occurred, in 3 stomach mucosa ulceration was diagnosed in the band pressure area, 3 reported heartburn and hyperacidity, and 4 suffered from emesis. In all aforementioned patients, body mass loss stopped and they reported lack of restriction after last band regulation. CONCLUSIONS: Surgical or endoscopic treatment in patients with a migrated band is an individual matter depending on the type and size of band dislocation, its clinical symptoms and the general state of the patient, but also on the experience of the operating team and the quality of the equipment.
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Cirugía Bariátrica/métodos , Migración de Cuerpo Extraño/cirugía , Gastroplastia/efectos adversos , Gastroplastia/instrumentación , Obesidad/cirugía , Tomografía Computarizada por Rayos X/métodos , Adulto , Índice de Masa Corporal , Femenino , Migración de Cuerpo Extraño/diagnóstico por imagen , Gastroplastia/métodos , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) is a useful surrogate marker of insulin resistance and cardiovascular risk factors. We aimed to assess the relationship between the TG/HDL-C ratio and insulin resistance (IR) and its usefulness in prediction of the metabolic syndrome (MS). This retrospective study involved 122 obese children with the mean age of 11.6±3 years and their 58 healthy lean peers. Anthropometric measurements, blood pressure, the plasma lipid profile and oral glucose tolerance test (OGTT) were analyzed. Based on the obtained results, the TG/HDL-C ratio and surrogate insulin resistance indices (HOMA-IR, FGIR, QUICKI, OGIS, Matsuda index) were calculated. The TG/HDL-C ratio positively correlated with weight, waist circumference, waist to hip ratio (WHR), lipid profile, HOMA-IR, fasting insulin and insulin measurements during OGTT, and negatively correlated with FGIR, QUICKI, OGIS, and the Matsuda index. Obese children with the TG/HDL-C ratio≥3 (47.5%) had higher values of WHR and HOMA-IR, and lower ones of FGIR, QUICKI, OGIS, and the Matsuda index when compared to their obese peers with the TG/HDL-C<3. The area under the curve (AUC) calculated for each insulin resistance index in prediction of the metabolic syndrome was the largest for the TG/HDL-C ratio (0.8936, 95% Cl:0.809-0.977, p=0.000). For 1 unit increase in the TG/HDL-C ratio, the odds for having MS increased by 2.09 times. The TG/HDL-C ratio is a good surrogate marker of insulin resistance in obese children. When comparing the usefulness of some IR markers in prediction of the metabolic syndrome, the TG/HDL-C ratio seems to be the best one and should be used in clinical practice to identify children at risk of metabolic syndrome development.
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HDL-Colesterol/sangre , Síndrome Metabólico/diagnóstico , Obesidad/sangre , Triglicéridos/sangre , Adolescente , Biomarcadores/sangre , Glucemia , Presión Sanguínea , Enfermedades Cardiovasculares/diagnóstico , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Síndrome Metabólico/sangre , Polonia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSES:: Some controversies exist on the effect of therapeutic thoracentesis (TT) on arterial blood oxygen tension. The aim of this study was to evaluate this issue using a previously developed virtual patient. METHODS:: The analysis was based and supported by clinical data collected during 36 TT. Pleural pressure and transcutaneous oxygen and carbon dioxide pressures (PtcO2 and PtcCO2) were measured during pleural fluid withdrawal. Arterial blood oxygen tension and arterial CO2 tension (PaO2 and PaCO2) were analysed in simulations that mimicked TT. Minute ventilation was adjusted to maintain arterial CO2 tension at a constant level unless arterial blood oxygen tension fell below 8 kPa. Specifically, the influence of hypoxic pulmonary vasoconstriction efficiency was tested. RESULTS:: In patients, PtcCO2 remained at an approximately constant level (average amplitude: 0.63 ± 0.29 kPa), while some fluctuations of PtcO2 were observed (amplitude: (1.65 ± 1.18 kPa) were observed. In 42% of patients, TT was associated with decrease in PtcCO2. Simulations showed the following: (a) there were similar PaO2 fluctuations in the virtual patient; (b) the lower the hypoxic pulmonary vasoconstriction efficiency, the more pronounced the PaO2 fall during fluid withdrawal; and (c) the lower the atelectatic lung areas recruitment rate, the slower the PaO2 normalization. The decrease in PaO2 was caused by an increase of pulmonary shunt. CONCLUSION:: Therapeutic thoracentesis may cause both an increase and a decrease in PaO2 during the procedure. Pleural pressure decrease, caused by pleural fluid withdrawal, improves the perfusion of atelectatic lung areas. If the rate of recruitment of these areas is low, a lack of ventilation causes the arterial blood oxygen tension to fall. Effective hypoxic pulmonary vasoconstriction may protect against the pulmonary shunt.
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Análisis de los Gases de la Sangre/métodos , Dióxido de Carbono/sangre , Oxígeno/sangre , Toracocentesis , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Entrenamiento SimuladoRESUMEN
Subatmospheric pleural pressure (Ppl), which is approximately -3 to -5 cmH2O at functional residual capacity (FRC) makes pleura a unique organ in the human body. The negative Ppl is critical for maintaining the lungs in a properly inflated state and for proper blood circulation within the thorax. Significant and sudden pleural pressure changes associated with major pleural pathologies, as well as therapeutic interventions may be associated with life-threatening complications. The pleural pressure may show two different values depending on the measurement method applied. These are called pleural liquid pressure and pleural surface pressure. It should also be realized that there are significant differences in pleural pressure distribution in pneumothorax and pleural effusion. In pneumothorax, the pressure is the same throughout the pleural space, while in pleural effusion there is a vertical gradient of approximately 1â¯cmâ¯H2O/cm in the pleural pressure associated with the hydrostatic pressure of the fluid column. Currently, two main methods of pleural pressure measurement are used: simple water manometers and electronic systems. The water manometers are conceptually simple, cheap and user-friendly but they only allow the estimation of the mean values of pleural pressure. The electronic systems for pleural pressure measurement are based on pressure transducers. Their major advantages include precise measurements of instantaneous pleural pressure and the ability to display and to store a large amount of data. The paper presents principles and details of pleural pressure measurement as well as the rationale for its use.