RESUMEN
Lower urinary tract dysfunction is common among neurological patients. Traditionally, the basic method of diagnosis is a complex urodynamic study. In recent years, many studies have focused on the search for new non-invasive diagnostic modalities. In particular, neurotrophins are considered as potential biological markers of a neurogenic bladder. AIM: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) and brain neurotrophic factor (BDNF) in MS patients as markers of detrusor overactivity. MATERIALS AND METHODS: The study comprised 20 patients with multiple sclerosis, who complained of voiding problems. The control group consisted of 20 people without neurological diseases, lower urinary tract symptoms and detrusor overactivity estimated by filling cystometry. Apart from standard laboratory tests, diagnostic evaluation included a complex urodynamic study, ultrasound of the urinary tract, cystoscopy, testing serum and urinary NGF and BDNF using the enzyme immunoassay. The diagnostic significance of neurotrophins was evaluated using ROC analysis. RESULTS: According to the ROC analysis, the diagnostic sensitivity and specificity of serum NGF as a marker of detrusor hyperactivity was 57% and 93%, respectively (for serum NGF more or equal 26 pg/ml). The quality of the test according to the expert scale of AUC values was "very good" (AUC=0.806). Detecting NGF in patients urine was less effective. The sensitivity and specificity were 52% and 40%, respectively (for NGF more or equal 6 pg/ml). The quality of the test according to the expert scale of AUC values was "average" (AUC=0.64). The serum BDNF demonstrated high sensitivity (90%) and low specificity (23%), AUC=0.56. The urinary BDNF was more informative, (AUC=0.65). The combination of all four markers provides a sensitivity of 85.7% and a specificity of 66.7% (AUC=0.824). CONCLUSIONS: Testing serum and urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity. The NGF is a highly specific biomarker, while the BDNF is highly sensitive. Combined testing for serum NGF and BDNF is most informative.
Asunto(s)
Esclerosis Múltiple/complicaciones , Factores de Crecimiento Nervioso , Vejiga Urinaria Neurogénica/sangre , Vejiga Urinaria Neurogénica/orina , Vejiga Urinaria Hiperactiva/sangre , Vejiga Urinaria Hiperactiva/orina , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/orina , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/orina , Factor de Crecimiento Nervioso/sangre , Factor de Crecimiento Nervioso/orina , Factores de Crecimiento Nervioso/sangre , Factores de Crecimiento Nervioso/orina , Curva ROC , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Hiperactiva/etiologíaRESUMEN
AIM: to estimate the expression of cell adhesion molecules E- and P-cadherin, as well as that of cadherin-catenin complexes in invasive lobular breast cancer (BC) cells. MATERIAL AND METHODS: 250 cases of postoperative material from patients diagnosed with invasive lobular BC were studied. The expressions of cell adhesion molecules E-cadherin, P-cadherin, ß-catenin, p120 catenin, and vimentin were determined by immunohistochemical assay in all cases. The examined cases were divided into molecular biological subtypes, based on the evaluation of estrogen receptors (ER), progesterone receptors (PR), HER-2/neu, and Ki-67 proliferative index. RESULTS: The membrane expression of E-cadherin on the tumor cells was found to be preserved in 93%; the cytoplasmic expression of ß-catenin and p120-catenin appeared in 60 and 72% of cases, respectively. The expression of P-cadherin was detected in 82% of cases. The coexpression of E- and P-cadherin was noted in 90% of all the examined cases. There was a correlation between the expression of E- and P-cadherins (V=0.34; p<0.05). CONCLUSION: The BC cells showed the coexpression of E- and P-cadherins, as well as release of the molecules ß- and p120-catenins into the cytoplasm of tumor cells, which leads to the activation of intracellular mechanisms for changing the structure of the cytoskeleton and the level of proliferation. The above-mentioned mechanisms are accompanied by the activation of epithelial-mesenchymal transition. The intracellular mechanisms resulted in progressive cancer and its metastasis.
Asunto(s)
Cadherinas/biosíntesis , Cateninas/biosíntesis , Neoplasias de la Mama Triple Negativas/genética , beta Catenina/biosíntesis , Cadherinas/genética , Cateninas/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica/genética , Pronóstico , Receptor ErbB-2/biosíntesis , Neoplasias de la Mama Triple Negativas/clasificación , Neoplasias de la Mama Triple Negativas/patología , Vimentina/biosíntesis , Vimentina/genética , beta Catenina/genética , Catenina deltaRESUMEN
The review gives data on the structure of cadherin cell adhesion molecules, their role in the body's development and malignant tumor progression. It describes cadherins that are considered to play the most important role in the development of a tumor process: E-, P-, and N-cadherins that belong to type I classical cadhedrins and VE-cadhedrin that does to type II cadherins. Particular emphasis is placed on the signal mechanisms with involvement of cadherins and cadherin-related molecules, which are realized in the body in health and in tumor transformation of cells.
Asunto(s)
Neoplasias de la Mama , Cadherinas/metabolismo , Transformación Celular Neoplásica , Proteínas de Neoplasias/metabolismo , Transducción de Señal , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Femenino , HumanosRESUMEN
E-cadherin is one of the most important cell adhesion molecules, which plays a key role in embryogenesis and adult tissues under normal conditions and during tumor development. Molecules of E-cadherin are located at the epitheliocyte surface and take part in the adhesion contacts formation which are a characteristic feature of epithelial tissues. The role of E-cadherin is not only in the maintenance of intercellular adhesion, but also in provision of cell proliferation and differentiation through participation in the realization of a number of signaling pathways, the main of which is the canonical Wnt signaling pathway. This review provides basic information regarding the role of E-cadherin in human ontogenesis in norm and pathology.
Asunto(s)
Cadherinas/metabolismo , Morfogénesis , Neoplasias/metabolismo , Cadherinas/genética , Adhesión Celular , Proliferación Celular , Células Epiteliales/metabolismo , Células Epiteliales/fisiología , Humanos , Transducción de SeñalRESUMEN
The paper analyzes 10 years' experience in HER2 status testing in breast cancer in Russia. The ASCO/CAP HER2 testing guidelines adaptable to the work of pathologists in Russia are considered.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama , Receptor ErbB-2 , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Inmunohistoquímica/instrumentación , Inmunohistoquímica/métodos , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estándares de Referencia , Federación de Rusia/epidemiología , TrastuzumabRESUMEN
The effect of supercompensation and the conditions of its origination have been analyzed using a special analytical solution of the equation of the overdamped Duffing oscillator. The threshold values of the functional shift after the exposure of a living organism to intensive external load have been found. If these values are exceeded, the restoration process goes through the stages of enhanced and lowered working capacity. Expressions for the times of transition to these phases after the onset of recovery and for the time of occurrence of the maxima of these phases have been obtained and analyzed.
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Relojes Biológicos , Modelos BiológicosRESUMEN
On the basis of the overdamped Duffing model, a technique for determining the key parameters of functional systems of the living body has been developed which characterizes its properties during recovery from standard physical load. As an example, the dynamics of restoration of pulse frequency is considered. The knowledge of these parameters allows one to predict the response of the living body to intensive external loads. This information can also be helpful for the optimization of the training process.
Asunto(s)
Adaptación Fisiológica , Modelos Biológicos , Animales , Fenómenos Biomecánicos , HumanosRESUMEN
The propagation of transverse-longitudinal acoustic pulses through a strained cubic crystal containing resonant paramagnetic impurities with effective spin S =1 is investigated. It is supposed that the pulses propagate under arbitrary angle with respect to the direction of the external static deformation parallel to the fourth-order symmetry axis. In this geometry, both the transverse and longitudinal components of the acoustic field have high-frequency and zero-frequency spectral components. We show that a pulse can propagate in modes different from the acoustic self-induced transparency. In particular, a pulse propagating in the mode of an acoustic self-induced supertransparency substantially changes the populations of the spin sublevels, but its group velocity remains almost equal to the linear velocity of the sound. If a pulse propagates in the acoustic extraordinary transparency mode, then its group velocity is substantially lower while the sublevel populations remain virtually invariant. Also, the modes of propagation under conditions of weakly excited spin transitions and large detuning of the pulse high-frequency components are identified.
RESUMEN
A semiphenomenological approach to the study of the adaptation of a particular functional system of the living organism to nonregular changes in the environmental parameter conjugated with this system was suggested. It was shown that the behaviour of the functional system under these conditions is similar to that of a macroparticle in the rotational Brownian motion. In the adaptation process, a phase of superadaptation at the smallest nonregular actions was revealed. Some examples supporting the occurrence of the superadaptation phase are presented.
Asunto(s)
Adaptación Fisiológica , Ambiente , Modelos Biológicos , Animales , Tolerancia al Ejercicio/fisiología , HumanosRESUMEN
A phenomenological nonlinear model, describing a reconstruction of the living organism after strong loading have been proposed. This model is describing a restitution dynamics of the organism functional state to the initial state, including a supercompensation stage. In a simplest (one-component) case this model is overdamping Duffing oscillator. It is shown that the mutation phenomena may be described as the phase transition within the framework of Landau-Khalatnikov approach. A generalized many-component nonlinear reconstruction model is proposed.
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Condicionamiento Físico Animal/fisiología , Animales , Metabolismo Energético , Modelos Biológicos , RatasRESUMEN
On the basis of the nonlinear model of the overdamped Duffing oscillator, the adaptation of the living organism to regular external loads (constant and periodical) was studied. It was shown that this model describes the stages of strain and resistance. In the resistance stage, a superadaptation phase may be observed, which exceeds by functional shift its asymptotic volume. This stage has a threshold character with respect to load. It was shown that the theoretical results coincide with the experimental data obtained under periodical loads. The conclusion about the existence of optimal load frequency, which leads to a maximum heating of the organism. The differences between the responses of organisms with strong and weak immunities to the harmonic actions were analyzed.
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Adaptación Fisiológica , Enfermedad , Salud , Modelos BiológicosRESUMEN
The authors show the possibility of determining the thickness of a histological section using a spectrophotometer with automatic recording of absorption spectrum. The thickness of the section in nanometers is calculated by graphic records of the sample interference pattern. Experimental setting has been defined which warrants stable results.