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Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5-7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly's development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood.
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The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.
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Cardiopatías Congénitas , Corazón , Humanos , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/etiología , Animales , Corazón/embriología , Corazón/crecimiento & desarrollo , Cresta Neural , Morfogénesis , OrganogénesisRESUMEN
The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.
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Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain based on tooth pulp stimulation. More specifically, we assessed the effects of intracerbroventricular (i.c.v.) and intraperitoneal (i.p.) administration of URB597 on the amplitude of evoked tongue jerks (ETJ) in rats. The levels of the investigated mediators anandamide (AEA), 2-arachidonyl glycerol (2-AG), Substance P (SP), calcitonin-gene-related peptide (CGRP), endomorphin-2 (EM-2) and fatty acid amide hydrolase (FAAH) inhibitor by URB597 and receptors cannabinoid type-1 receptors (CB1R), cannabinoid type-2 receptors (CB2R) and µ-opioid receptors (MOR) were determined in the mesencephalon, thalamus and hypothalamus tissues. We have shown that increasing endocannabinoid AEA levels by both central and peripheral inhibition of FAAH inhibitor by URB597 has an antinociceptive effect on the trigemino-hypoglossal reflex mediated by CB1R and influences the activation of the brain areas studied. On the other hand, URB597 had no effect on the concentration of 2-AG in the examined brain structures and caused a significant decrease in CB2R mRNA expression in the hypothalamus only. Tooth pulp stimulation caused in a significant increase in SP, CGRP and EM-2 gene expression in the midbrain, thalamus and hypothalamus. In contrast, URB597 administered peripherally one hour before stimulation decreased the mRNA level of these endogenous neuropeptides in comparison with the control and stimulation in all examined brain structures. Our results show that centrally and peripherally administered URB597 is effective at preventing orofacial pain by inhibiting AEA catabolism and reducing the level of CGRP, SP and EM-2 gene expression and that AEA and 2-AG have different species and model-specific regulatory mechanisms. The data presented in this study may represent a new promising therapeutic target in the treatment of orofacial pain.
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Benzamidas , Péptido Relacionado con Gen de Calcitonina , Carbamatos , Percepción del Dolor , Amidohidrolasas/genética , Animales , Benzamidas/farmacología , Benzamidas/uso terapéutico , Carbamatos/farmacología , Carbamatos/uso terapéutico , Endocannabinoides/metabolismo , Dolor Facial/tratamiento farmacológico , Percepción del Dolor/efectos de los fármacos , Alcamidas Poliinsaturadas/metabolismo , ARN Mensajero , Ratas , Receptor Cannabinoide CB1/efectos de los fármacos , Receptores de Cannabinoides/efectos de los fármacosRESUMEN
Introduction: A number of studies on using both three-dimensional printing and virtual models in assessment of aortic coarctation have been published, yet none of them uses virtual modelling as a planning tool in a blind retrospective analysis. Aim: Assessment of virtual modelling and virtual reality in planning interventional treatment of aortic coarctation. Material and methods: The study involved computed tomography scans of 20 patients performed prior to interventional treatment of aortic coarctation, which were used to create a virtual three-dimensional model of the aorta in Materialise Mimics. A group of potential stents was modelled in Materialise 3-Matic and complete simulations were assessed in Mimics Viewer using a virtual reality headset in order to choose an optimal stent, which was later compared with the implanted one. Results: In 5 cases identical or very similar stents were proposed, in 12 cases simulations had slight, potentially avoidable misestimations either in stent length or diameter, and in 3 cases differences were more considerable. Overall, in 14 cases the location of the stent was concordant between the simulation and reality and in the remaining 6 cases the simulated stent was located lower than the actual one. Conclusions: The method of computer modelling provided a satisfactory success rate of predicting the possible stents to use during the procedure. Differences in chosen stents may have been caused by individual experience in interventional cardiology, the lack of availability of certain stents in the heart catheterization laboratory, the lack of information about the diameter of the vascular access and differences in dimensions measured on the model, tomography and angiography.
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Endometriosis is a chronic gynecological disease, affecting up to 10% of reproductive-age women. The exact cause of the disease is unknown; however, it is a heritable condition affected by multiple genetic, epigenetic, and environmental factors. Previous studies reported variations in the epigenetic patterns of numerous genes known to be involved in the aberrant modulation of cell cycle steroidogenesis, abnormal hormonal, immune and inflammatory status in endometriosis, apoptosis, adhesion, angiogenesis, proliferation, immune and inflammatory processes, response to hypoxia, steroidogenic pathway and hormone signaling are involved in the pathogenesis of endometriosis. Accumulating evidence suggest that various epigenetic aberrations may contribute to the pathogenesis of endometriosis. Among them, DNA methyltransferases, histone deacetylators, and non-coding microRNAs demonstrate differential expression within endometriotic lesions and in the endometrium of patients with endometriosis. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may contribute to the discovery of a useful prognostic biomarker, which could aid in the future earlier detection, timely diagnosis, and initiation of a new approach to the treatment of endometriosis, as well as inform us about the effectiveness of treatment and the stage of the disease. As the etiology of endometriosis is highly complex and still far from being fully elucidated, the presented review focuses on different approaches to identify the genetic and epigenetic links of endometriosis and its pathogenesis.
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The most common histological type of thyroid cancer is papillary thyroid carcinoma (PTC). Radical resection of the thyroid gland is currently the recommended method of treatment. Almost 75% of thyroidectomies performed just for diagnostic purposes are benign. Thus, the confirmation of innovative and more precise noninvasive biomarkers holds promise for the detection of PTC, which may decrease the number of unnecessary thyroid lobectomies. In this work, using the droplet digital PCR (ddPCR) method, we have analyzed the level of five miRNAs (let-7a, let-7c, let-7d, let-7f, and let-7i) in the plasma of patients with PTC and compared them with those of a healthy control group to investigate whether miRNAs also have value in the management of PTC. Levels of four miRNAs, namely let-7a, let-7c, let-7d, and let-7f, were significantly higher in PTC patients than healthy controls. Thus, the analysis of circulating let-7 can be a useful tool and support the currently used methods for PTC diagnosis. However, our observation requires further research on a larger patient group.
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Papillary thyroid cancer is the most common thyroid cancer type. However, diagnostics based on fine needle biopsy cannot make a definitive diagnosis in 25% of thyroid nodules. Additionally, approximately 70% to 80% of thyroid lobectomies performed just for diagnostic purposes are benign. Despite this, biopsy still remains the main method of evaluation of thyroid nodules. Cell-free DNA (cf-DNA) measurement could give a new diagnostic opportunities which may reduce the number of unnecessary thyroid procedures. In this study, using a qPCR, we have examined the nuclear cf-DNA and mitochondrial cf-DNA in the plasma of 32 patients. We have found that the level of nuclear cf-DNA is almost 2-fold increased (median 3 089 vs. 1 872, p = 0.022), whereas mitochondrial cf-DNA content was significantly decreased in respect to healthy controls (median 44 992 vs. 92 220, p = 0.010). The ROC curve analysis showed high specificity for nuclear cf-DNA and mitochondrial cf-DNA, which may serve as a useful tool to decrease the number of unneeded surgeries. Our study reports the first epidemiological evidence for lower mitochondrial cf-DNA content in the patient group, what suggests that apart from nuclear cf-DNA also mitochondrial cf-DNA is affected by disease development.
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ADN Mitocondrial/sangre , ADN/sangre , Cáncer Papilar Tiroideo/sangre , Neoplasias de la Tiroides/sangre , Adulto , Anciano , Anciano de 80 o más Años , Núcleo Celular , Ácidos Nucleicos Libres de Células/sangre , Femenino , Humanos , Ganglios Linfáticos , Masculino , Persona de Mediana Edad , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Adulto JovenAsunto(s)
Defecto del Tabique Aortopulmonar/complicaciones , Circulación Colateral , Tromboembolia/complicaciones , Defecto del Tabique Aortopulmonar/diagnóstico por imagen , Defecto del Tabique Aortopulmonar/tratamiento farmacológico , Defecto del Tabique Aortopulmonar/cirugía , Femenino , Defectos del Tabique Interventricular/complicaciones , Defectos del Tabique Interventricular/diagnóstico por imagen , Humanos , Lactante , Atresia Pulmonar/complicaciones , Atresia Pulmonar/diagnóstico por imagen , Tromboembolia/diagnóstico por imagen , Tromboembolia/tratamiento farmacológico , Tromboembolia/cirugíaRESUMEN
Analysis of the problem of surgical pain is important in view of the fact that the success of surgical treatment depends largely on proper pain management during the first few days after a cardiosurgical procedure. Postoperative pain is due to intraoperative damage to tissue. It is acute pain of high intensity proportional to the type of procedure. The pain is most intense during the first 24 hours following the surgery and decreases on subsequent days. Its intensity is higher in younger subjects than elderly and obese patients, and preoperative anxiety is also a factor that increases postoperative pain. Ineffective postoperative analgesic therapy may cause several complications that are dangerous to a patient. Inappropriate postoperative pain management may result in chronic pain, immunosuppression, infections, and less effective wound healing. Understanding and better knowledge of physiological disorders and adverse effects resulting from surgical trauma, anesthesia, and extracorporeal circulation, as well as the development of standards for intensive postoperative care units are critical to the improvement of early treatment outcomes and patient comfort.
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BACKGROUND: Liquid biopsy is a minimally invasive detection method for molecular biomarkers such as miRNA and cell free DNA in body fluids. Deregulations of miRNA are involved in papillary thyroid carcinoma (PTC), one the most common endocrine malignancy. The most widespread common mutations detected in papillary thyroid cancers are BRAF mutations. Many studies indicate that the BRAF mutation is related to deregulation of miRNA. p53 has an important role in cell cycle control, DNA repair and apoptosis. Moreover, the p53 can regulate the expression of miRNAs and thus participate in thyroid oncogenesis. OBJECTIVE: In this review, we briefly summarize the present state of knowledge about miRNA, BRAF and p53 mutation in the development of PTC and the possibility of using detecting BRAF mutation and miRNA expression in liquid biopsy. RESULTS: The use of the plasma miRNA expression profile in combination with the BRAF mutation analysis in cf-DNA may be a valuable tool in management of PTC. CONCLUSION: Numerous molecular variation characterize recent diagnostic and prognostic markers and therapeutic targets for this type of cancer, which offer unique chances for further research and clinical development of innovative treatment strategies for thyroid cancer.
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Biomarcadores de Tumor/genética , Cáncer Papilar Tiroideo/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Ácidos Nucleicos Libres de Células/genética , Detección Precoz del Cáncer , Regulación Neoplásica de la Expresión Génica , Humanos , Biopsia Líquida , MicroARNs/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND AND PURPOSE: Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia. The specific effects of these compounds within the orofacial region are largely unknown. In this study, we tried to determine whether an increase in cannabinoid and opioid concentration in the CSF affects impulse transmission between the motor centres localized in the vicinity of the third and fourth cerebral ventricles. EXPERIMENTAL APPROACH: The study objectives were realized on rats using a method that allows the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was a measure of the effect of neurotransmitters on neural structures. KEY RESULTS: Perfusion of cerebral ventricles with anandamide (AEA), endomorphin-2 (EM-2), URB597, an inhibitor of fatty acid amide hydrolase (FAAH) and JZL195, a dual inhibitor of FAAH and monoacylglycerol lipase (MAGL) reduced the ETJ amplitude. The antinociceptive effect of AEA, EM-2, URB597 and JZL195 was blocked by CB1 receptor antagonist, AM251 and by µ receptor-antagonist, ß-funaltrexamine. In contrast to AEA, 2-arachidonoylglycerol alone did not decrease ETJ amplitude. CONCLUSIONS AND IMPLICATIONS: We demonstrated that in the orofacial area, analgesic activity is modulated by AEA and that EM-2-induced antinociception was mediated by µ and CB1 receptors. The action of AEA and EM-2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand. Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain.
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Analgésicos Opioides/farmacología , Endocannabinoides/farmacología , Dolor Facial/tratamiento farmacológico , Percepción del Dolor/efectos de los fármacos , Amidohidrolasas/antagonistas & inhibidores , Analgésicos Opioides/administración & dosificación , Animales , Ventrículos Cerebrales/efectos de los fármacos , Ventrículos Cerebrales/metabolismo , Modelos Animales de Enfermedad , Endocannabinoides/administración & dosificación , Masculino , Monoacilglicerol Lipasas/antagonistas & inhibidores , Ratas , Ratas Long-Evans , Receptor Cannabinoide CB1/efectos de los fármacos , Receptor Cannabinoide CB1/metabolismo , Receptores Opioides mu/efectos de los fármacos , Receptores Opioides mu/metabolismoRESUMEN
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC.
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Carcinoma/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Familia de Multigenes , Neoplasias de la Tiroides/genética , Carcinoma Papilar , Transformación Celular Neoplásica/genética , Perfilación de la Expresión Génica , Humanos , MicroARNs/sangre , Mutación , Cáncer Papilar Tiroideo , Transcripción Genética , TranscriptomaRESUMEN
Energy intake and expenditure are regulated by a complex network of neurochemical systems. The results of numerous studies have provided information about receptors involved, the sites of action within the brain and interactions between various systems, including opioid and cannabinoid, in regulation of energy balance. This review summarizes our present knowledge on the opioid and cannabinoid system appetite and satiety pathways. The involvement of the three main types of opioid receptors (MOR, DOR and KOR) and CB1 cannabinoid receptor, as well as the endogenous ligands of these receptors in food intake is documented. Finally, the use of opioid-cannabinoid system interactions as a new approach in the search for the next generation therapeutics controlling food intake disorders is discussed.
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Analgésicos Opioides/farmacología , Apetito/efectos de los fármacos , Cannabinoides/farmacología , Ingestión de Alimentos/efectos de los fármacos , Animales , Humanos , Receptores Opioides/metabolismoRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary arterioles with an unfavourable prognosis. AIM: To evaluate survival and prognostic factors in patients with PAH diagnosed and treated at a single centre in the years 20042013. METHODS: The study included 55 children (33 girls; 66%, 22 boys; 33%), with an average age 6.2 ± 6.0 years, with idiopathic PAH n = 23 (42%), PAH associated with systemic-to-pulmonary shunts n = 17 (31%), and PAH after corrective cardiac surgery n = 15 (27%). Forty-seven of them (87%) were treated with advanced therapy. RESULTS: During the follow-up with an average time of 5.6 ± 4.7 years 15 (27.3%) children died. The one-, three-, five-, and ten-year survival was, respectively, 83.1%, 77.1%, 70.7%, and 65.2%. The analysis of the survival curves revealed a better prognosis in patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level < 605 pg/mL (p = 0.024) and a higher probability of survival of three and five years in children at baseline I/II World Health Organisation functional class (WHO-FC). The higher risk of death was associated with a higher pressure in the right atrium (HR 1.23, p < 0.01) and higher pulmonary resistance (HR 1.1, p < 0.01), whereas no history of syncope had a better prognosis (HR 0.31, p = 0.03). CONCLUSIONS: Survival in the study group was comparable to the currently published register data. Mortality risk factors were connected with the severity of the disease at diagnosis.
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Hipertensión Pulmonar/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/terapia , Lactante , Masculino , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Factores de RiesgoRESUMEN
Disorders involving the orofacial area represent a major medical and social problem. They are a consequence of central nociceptive processes associated with stimulation of the trigeminal nerve nucleus. A rat model of trigeminal pain, utilizing tongue jerks evoked by electrical tooth pulp stimulation during perfusion of the cerebral ventricles with various neuropeptide solutions, can be used in the pharmacological studies of nociception in orofacial area. The investigated neuropeptides diffuse through the cerebroventricular lining producing an analgesic effect either directly, through the trigemino-hypoglossal reflex arc neurons or indirectly through the periaqueductal central gray, raphe nuclei or locus coeruleus neurons. The aim of this review is to present the effect of pharmacological activity of various neuropeptides affecting the transmission of the sensory information from the orofacial area on the example of trigemino-hypoglossal reflex in rats.
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Dolor Facial , Neuropéptidos/farmacología , Nocicepción/efectos de los fármacos , Reflejo/efectos de los fármacos , Tegmento Mesencefálico/efectos de los fármacos , Núcleo Espinal del Trigémino/efectos de los fármacos , Animales , Dolor Facial/tratamiento farmacológico , Dolor Facial/patología , Dolor Facial/fisiopatología , Humanos , Ratas , Transmisión Sináptica/efectos de los fármacos , Núcleo Espinal del Trigémino/fisiologíaRESUMEN
BACKGROUND: A Fontan-type operation, i.e. a connection of the systemic veins and pulmonary arteries without subpulmonary ventricle, with different surgical techniques, is nowadays the only treatment option for patients with a functionally univentricular heart (UVH). Understanding the development of pulmonary arteries in patients who are considered for the Fontan procedure is important clinically. AIM: To evaluate the development of pulmonary arteries in patients with univentricular circulation. METHODS: Between 1995 and 2007, 111 patients underwent a bidirectional Glenn procedure. In all patients, preoperative catheterisation was performed to assess the anatomy and haemodynamics of UVH, especially the size of the pulmonary arteries. Ninety nine patients were included in the bidirectional Glenn group; 62 of these underwent repeat catheterisation before Fontan completion. The late results, after one stage extracardiac total cavopulmonary anastomosis performed in 24 patients between 1992 and 2002, were reinvestigated (one-stage Fontan group). We assessed the changes in the McGoon ratio and Nakata index for the whole cohort of patients. McGoon ratio is the sum of the diameter of pulmonary arteries divided by the diameter of the aorta. Nakata index is the sum of the cross-sectional area of the pulmonary arteries divided by the body surface area. RESULTS: During cardiac catheterisation prior to Glenn procedure, the mean Nakata index was 351.9 (range 131.2-886) mm2/m2 and was higher in patients with increased pulmonary flow (p = 0.0135). Mean McGoon ratio was 2.5 (range 1.1-4.9). An average 40.3 months after Glenn procedure, the Nakata index and McGoon ratio decreased significantly to 226.4 ± 125 mm²/m² (p < 0.003), and to 2.14 ± 0.58 (p < 0.008) respectively. In the group of patients after one-stage Fontan in late follow-up, mean 7.4 years after procedure, the Nakata index decreased from 318.7 ± 159.1 mm²/m² to 120 ± 40 mm²/m² (p < 0.0001) and McGoon ratio from 2.4 ± 0.6 to 1.4 ± 0.27 (p < 0.0001). Only size of pulmonary arteries before Glenn procedure, in the bidirectional Glenn group, or before Fontan operation, in the one-stage Fontan group,were inversely correlated with the changes of size of pulmonary arteries (p = 0.0015 and p = 0.0012). CONCLUSIONS: The relative decrease of the size of pulmonary arteries in the inter-stage period (between bidirectional Glenn anastomosis and Fontan completion) and after Fontan completion may indicate that pulmonary artery sizes should probably not bean absolute limiting factor in the decision on treatment of functionally UVH patients, especially at the stage of Fontan approach.
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Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/cirugía , Arteria Pulmonar/crecimiento & desarrollo , Niño , Preescolar , Femenino , Estudios de Seguimiento , Procedimiento de Fontan , Ventrículos Cardíacos/fisiopatología , Hemodinámica , Humanos , Lactante , Recién Nacido , Masculino , Periodo Posoperatorio , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Resultado del TratamientoRESUMEN
Our previous studies demonstrated that tooth pulp stimulation increases the pain threshold, whereas stimulation of the periaqueductal central gray (PAG) has the opposite effect. The aim of this study was to investigate the effect exerted by electrical stimulation of the nociceptive afferent terminals in the tooth pulp and analgesic electrical stimulation of the PAG on the release of immunoreactive ß-endorphin (ß-EP-IR) into the cerebrospinal fluid (CSF) and artificial cerebrospinal fluid (aCSF) perfusing the cerebral ventricles in rat, and to establish whether during such stimulation the µ-opioid receptor (MOR) was activated. The tongue jerk reflex was induced by dental pulp stimulation in rats under chloralose anesthesia. CSF was collected from the cerebello-medullary cistern, and then 30-minute perfusions of the lateral ventricles with aCSF were conducted with collection of perfusate portions from the cerebello-medullary cistern at rest (control), during electrical tooth pulp stimulation evoking the nociceptive tongue jerk reflex and during inhibition of that reflex with simultaneous stimulation of tooth pulp and the PAG. In the second series of experiments, a MOR-selective antagonist, ß-funaltrexamine (ß-FNA) was perfused through the cerebral ventricles 10min before tooth pulp stimulation. ß-EP-IR was determined in the collected CSF and aCSF perfusates by radioimmunoassay (RIA). Stimulation of tooth pulp with electrical impulses resulted in a significant increase of ß-EP-IR. On the other hand, simultaneous tooth pulp and PAG stimulation inhibited ß-EP-IR release into the fluid perfusing the cerebral ventricles. ß-FNA blocked evoked tongue jerks (ETJ) induced by PAG stimulation, but no enhancing effect of ß-FNA on ß-EP-IR release into the perfusate was observed. The obtained results indicate that stimulation of the tooth pulp increases ß-EP release significantly, whereas PAG stimulation significantly inhibits ß-EP-IR release into the CSF, and that these effects are mediated by MOR. The results of the experiments allow to conclude that endogenous ß-EP, released as a result of electrical tooth pulp stimulation in orofacial pain, diffuses through the cerebroventricular ependyma into the CSF and exerts a modulatory effect, mediated by MOR, alterating the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve.
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Ventrículos Cerebrales/metabolismo , Líquido Cefalorraquídeo/química , Pulpa Dental/metabolismo , Umbral del Dolor/fisiología , Sustancia Gris Periacueductal/metabolismo , betaendorfina/metabolismo , Animales , Pulpa Dental/inervación , Estimulación Eléctrica , Masculino , Radioinmunoensayo , Ratas , Ratas Long-Evans , Receptores Opioides mu/metabolismo , Reflejo/fisiologíaRESUMEN
Nociceptive stimulation has been considered to affect the expression of genes encoding endogenous neuropeptides and their receptors. The effect of electric stimulation of the tooth pulp and/or periaqueductal gray (PAG) in rats on mRNA levels of the selected neuropeptides and opioid receptors (ORs) was investigated in comparison with control group, without stimulation. The levels of mRNA for the selected neuropeptides: galanin (GAL), vasopressin (AVP), oxytocin (OT), substance P (SP), somatostatin (SOM), vasoactive intestinal peptide (VIP), endomorphin-2 (EM-2), and opioid receptors: MOR, DOR and KOR in mesencephalic, hypothalamic and thalamic tissues were determined by real-time PCR. It was demonstrated that in the control group expression of the tested neuropeptides was at a very low level in the mesencephalon and thalamus, but at the higher level in the hypothalamus. The highest expression of ORs was observed in the mesencephalon. Nociceptive tooth pulp stimulation had the strongest effect in the hypothalamus, elevating mRNA levels of all tested neuropeptides except SOM. Electric stimulation of PAG either did not change or down-regulated mRNA levels of the neuropeptides in the cerebral structures. Simultaneous stimulation of PAG and tooth pulp either did not affect mRNA levels of the investigated neuropeptides or caused their slight decrease versus tooth pulp stimulation. The noxious stimulation of tooth pulp increased also the levels of OR mRNAs, while stimulation of PAG had the opposite effect. The above results demonstrated that tooth pulp stimulation significantly up-regulated the mRNA levels for a number of neuropeptides and all three types of ORs in the rat brain, which would result in more potent antinociception. In contrast, PAG stimulation down-regulated the mRNA levels of several neuropeptides and ORs in the cerebral tissues, which would cause decreased synthesis of ORs. The obtained results represent a new insight into the mechanism of orofacial pain.
Asunto(s)
Cavidad Pulpar/metabolismo , Diencéfalo/metabolismo , Dolor Facial/genética , Neuropéptidos/genética , Sustancia Gris Periacueductal/fisiología , Receptores Opioides/genética , Animales , Cavidad Pulpar/inervación , Diencéfalo/citología , Regulación hacia Abajo/genética , Estimulación Eléctrica/efectos adversos , Estimulación Eléctrica/métodos , Dolor Facial/metabolismo , Regulación de la Expresión Génica/genética , Hipotálamo/citología , Hipotálamo/metabolismo , Masculino , Neuropéptidos/biosíntesis , Nociceptores/citología , Nociceptores/metabolismo , Sustancia Gris Periacueductal/metabolismo , ARN Mensajero/biosíntesis , Ratas , Ratas Long-Evans , Receptores Opioides/biosíntesis , Tálamo/citología , Tálamo/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
Modified Blalock-Taussig (B-T) shunt occlusion results in a sudden reduction of pulmonary vascular perfusion, causing dramatic saturation drop and cyanosis which pose a direct hazard to a child's life. The results of percutaneous local r-tpa infusion, balloon angioplasty and additionally stent implantation in obstructed modified B-T shunts were studied to assess their role as an alternative to a re-do surgery. We outline two pediatric centers' experience (period 2004-2008) regarding the effectiveness of various emergency treatment methods for occlusion or critical stenosis of systemic-to-pulmonary arterial shunts in 23 children. Local r-tpa infusion via catheter was performed in 12/23 patients, balloon angioplasty in 22/23 and additionally stent implantation in 3/23 children. Procedures were successful in 22/23 patients (96%), with an increase in arterial saturation [average: 30%; standard deviation (S.D.) 15%; Shapiro-Wilk test; dependent t-test-P<0.01]. Unrestricted contrast flow was achieved in 18 patients, reduced central flow in three and minimal flow in one child. Neither local nor systemic complications occurred. Our experience demonstrates the possibility of successful early shunt recanalization with the use of local thrombolytic therapy combined with the balloon angioplasty. The presence of old fixed thrombus with neointimal hypertrophy in the shunt constitutes an indication for endovascular stent implantation.