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1.
Soft Matter ; 15(43): 8886-8895, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31617556

RESUMEN

There has been strong experimental evidence that molecules of some dyes in an anisotropic solvent, nematic liquid crystal, form aggregates. We present a detailed experimental analysis of the light-induced director reorientation (DR) in a dye-doped nematic liquid crystal (known as the Jánossy effect) and a theoretical model of its strong enhancement based on the aggregates' interaction. The DR transition is found to be very different from the Frederiks effect. If the light polarization is normal to the director, the transition is jump-like first order. Moreover, light polarization along the director also induces a DR which is a smooth second order transition with a very low threshold intensity. The theoretical model which explains these effects is based on the idea that dye molecules form rodlike supramolecular aggregates. The aggregates interact via the director distortions and their effective diameter gets certain field-dependence. As a result, the related entropy depletion depends on the light intensity and polarization and can be decreased by a certain DR along with the aggregate subsystem. This entropy gain is proportional to the square of light intensity which is a two-photon effect: the first resonance photon excites the dye molecule and the second photon polarizes the aggregate. This is in line with the experimental dependence of the critical intensity on the sample thickness. A special experiment shows that the effect is not connected with a possible heat-induced isotropic phase and hydrodynamic motion.

2.
Phys Rev E Stat Nonlin Soft Matter Phys ; 84(3 Pt 1): 031702, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22060385

RESUMEN

A spherical colloid with the tangential surface nematic director, aligned along the surface meridians, is known as a planar elastic quadrupole. The azimuthal anchoring, however, can induce a deviation of the planar director from the meridional lines. We show that a helical component of the planar surface director at the spherical surface of a planar quadrupole removes all the reflection symmetry planes and gives rise to a chiral elastic dipolar component. Using an ansatz approach, we consider the interplay between the quadrupole and anchoring-induced chiral dipole components. The chirality is enhanced by the bend-twist anisotropy. The interaction of the chiral components changes the attraction directions of two such colloids. In particular, a point appears at which the quadrupolar repulsion is balanced by the dipolar attraction.

3.
Phys Rev E Stat Nonlin Soft Matter Phys ; 83(4 Pt 1): 041709, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21599188

RESUMEN

Spherical colloidal particles with normal and tangential surface director alignment in a nematic liquid crystal induce elastic quadrupoles of opposite signs that attract one another along and perpendicular to the director. We utilize this unique angular profile of the mixed quadrupolar interaction to build 2D crystals with square lattices by laser tweezers.

4.
Phys Rev E Stat Nonlin Soft Matter Phys ; 83(2 Pt 1): 021701, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21405852

RESUMEN

In spite of the analogy to the electrostatics, the three-dimensional colloidal nematostatics is substantially different in both its mathematical structure and its physical implications. The general tensorial structure of elastic multipoles derived in V. M. Pergamenshchik and V. O. Uzunova [Eur. Phys. J. E 23, 161 (2007); Phys. Rev. E 76, 011707 (2007)] allows for a classification of different types of colloids in the nematostatics. In comparison to their electrostatic counterparts, the elastic multipoles have one extra tensorial index. Based on this structure, we identify possible types of elastic dipoles. An elastic dipole is characterized by three coefficients--isotropic strength, anisotropy, and chirality--and a two-component vector along the unperturbed director. The relationship between the dipole type and symmetry groups is established and sketches of various representative types of dipolar colloids are given. Instead of a single electric dipole, in the nematostatics there are four different pure types (dipolar singlets) and eight mixed types of elastic dipoles (one quintet, one quartet, two triplets, and four doublets). It is shown that the full symmetry of the colloid-induced director field and the colloid's shape (body) symmetry determine different dipole components. For instance, a helicoidal component of the anchoring easy axes can make a chiral elastic dipole of a colloid with the quadrupolar shape symmetry. The interaction potentials for different singlet and doublet dipoles are derived and illustrated in terms of the dipolar dyads and elastic Coulomb law. We argue that multipole parameters must be found by pure numerical means, as from ansatz director distributions one can find only orders of their magnitudes.

5.
Khirurgiia (Sofiia) ; (1): 22-7, 2011.
Artículo en Búlgaro, Inglés | MEDLINE | ID: mdl-23847798

RESUMEN

Papillary lesions of the mammary gland represent a serious disease and incorporate a broad spectrum of lesions. The goal of the current article is to reveal the diagnostic methods and therapeutic behavior in patients with pathological discharge from the nipple of the mammary gland. In this article we present 15 cases of histologically proven mammary gland papilloma. Mammographic, ultrasonographic and cytologic methods are applied for diagnostic specification. The chosen therapeutic behavior in all of the women is surgical. We take into consideration the possibilities of the different diagnostic methods as well as the therapeutic behavior-conservative or surgical approach. We reckon that when there is suspicion for mammary gland papilloma a surgical intervention is necessary to be carried out--due to the functional discomfort and due to the possibility intraductal carcinoma in situ to be missed out in some cases.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Glándulas Mamarias Humanas/patología , Glándulas Mamarias Humanas/cirugía , Papiloma/diagnóstico , Papiloma/cirugía , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Femenino , Humanos , Persona de Mediana Edad , Papiloma/patología , Adulto Joven
6.
Khirurgiia (Sofiia) ; (2-3): 15-8, 2010.
Artículo en Búlgaro | MEDLINE | ID: mdl-21972689

RESUMEN

UNLABELLED: Despite the new methods of treatment during the last two decades, prognosis in lung cancer remains unfavourable. Only 20-25% of the patients are suitable for surgery, and the surgical resection is the unique alternative with curable intent. The extent of resection is an important prognostic factor in lung cancer patients. MATERIAL AND METHODS: We present 440 patients with non-small cell lung cancer, radically operated in the Clinic of Thoracic and abdominal surgery of University Hospital "St.George" - Plovdiv for the period 01.01.1997 - 01.09.2004.191 underwent lobectomy, 12 - limited resection, 39 - bilobectomy, and 198 - pneumonectomy. RESULTS: 63 patients underwent lobectomy for stage I, and the 5-year survival was 63.49%. For the 12 patients with limited resection we found mean time of survival of 50 months, and the 5-year survival was 50%.331 of our patients were in stage II and III. 123 of them underwent lobectomy--the 5-year survival was 28.46%. 208 patients underwent bilobectomy and pneumonectomy--the 5-year survival in this group was 17.79%. CONCLUSIONS: In conclusion we found that the extent of resection is an important prognostic factor for lung cancer patients in stage I. The patients submitted to lobectomy have better survival compared with those submitted to limited resection. The survival is better for the group of patients who underwent lobectomy,compared with the one for the group with bilobectomy and pneumonectomy, which is probably due to the earlier stage of the disease.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Pulmón/cirugía , Neumonectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Bulgaria , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Pulmón/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Adulto Joven
7.
Khirurgiia (Sofiia) ; (1): 32-5, 2010.
Artículo en Búlgaro | MEDLINE | ID: mdl-21972702

RESUMEN

SUMMARY: There are over 150 prognostic factors in lung cancer, which allow to predict the outcome of the disease.Many molecular factors are known to have independent prognostic significance. At present these factors are not routinely used in the clinical practice, but they may play an important role in the future for precise individual prognosis. MATERIAL AND METHODS: The study included 122 patients with non-small cell lung cancer.Using immunohistochemistry we examined the expression of estrogen receptors--ERalpha and Erbeta. RESULTS: The median time of survival depending on the expression of Eralpha was 31 months, while for Erbeta was 73 months. CONCLUSIONS: Erbeta is a positive prognostic factor in patients with non-small cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Receptor alfa de Estrógeno/análisis , Receptor beta de Estrógeno/análisis , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Pulmón/patología , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Femenino , Humanos , Inmunohistoquímica , Pulmón/metabolismo , Pulmón/cirugía , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia
8.
Khirurgiia (Sofiia) ; (1): 40-3, 2010.
Artículo en Búlgaro | MEDLINE | ID: mdl-21972704

RESUMEN

The goal of the current article is to point the role of the different methods of surgical behavior in cases of mammary gland formations which have been ultrasonographically and mammographically diagnosed as cysts. Thirty-four women, clinically, ultrasonographicaly and mammographicaly diagnosed with cysts, are taken under consideration. Fine needle biopsy is carried out in all of the cases and the cysts' contents are cytologically and microbiologically tested. In 16 of the cases, puncture followed by pneumatocele represents the definitive treatment. In the end of the puncture, a control mammography is performed. Eighteen of the patients undergo surgical treatment due to the density of the cysts' contents, presence of bloody discharge, presence of a bilocular cyst and relapse following the puncture. As a result of the surgical treatment of 18 patients and of the histology are found as follows: benign cysts (13), carcinoma (1), papilloma (1), sclerotic adenosis (1), ADH (1), epidermoid cyst (1).


Asunto(s)
Quiste Mamario/patología , Quiste Mamario/cirugía , Glándulas Mamarias Humanas/patología , Glándulas Mamarias Humanas/cirugía , Adulto , Anciano , Biopsia con Aguja , Quiste Mamario/diagnóstico por imagen , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Ultrasonografía Mamaria
9.
Phys Rev E Stat Nonlin Soft Matter Phys ; 79(2 Pt 1): 021704, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19391762

RESUMEN

The new area of nematic colloidal systems (or nematic emulsions) has been greatly guided by the fruitful analogy between the colloidal nematostatics and electrostatics. The elastic charge density representation of the colloidal nematostatics [V. M. Pergamenshchik and V. O. Uzunova, Eur. Phys. J. E 23, 161 (2007); Phys. Rev. E 76, 011707 (2007)] develops this analogy at the level of charge density and Coulomb interaction. It shows, however, that the colloidal nematostatics in three dimensions substantially differs from the electrostatics both in its mathematical structure and physical implications: the elastic charge and multipoles are dyads; similar charges attract while opposite charges repel each other, and so on. In this paper we consider the interaction between an elastic charge and elastic dipole with a nematic surface (wall) at which the director alignment is fixed. Using the mirror image method of electrostatics as a guiding idea, we develop the mirror image method in the nematostatics for arbitrary director tilt at the wall. A wall is shown to induce a repulsive 1R{4} force on the elastic dipole which, in general, is accompanied by its reorientation. External torque on the colloid induces an elastic charge therein and triggers switching to the 1R{2} repulsion. The dyadic nature of an elastic dipole is shown to be essential: a particle-wall interaction potential cannot be obtained in phenomenological theories with a single component dipole. In the introductory sections we discuss connection between the director-mediated interaction in two and three dimensions and the electrostatic interaction and consider different symmetries of elastic dipoles. Conservation of the torque components exerted upon colloids is shown to play the role of Gauss' theorem and determines the elastic charge dyad.

10.
Phys Rev E Stat Nonlin Soft Matter Phys ; 77(4 Pt 1): 041703, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18517639

RESUMEN

We report an observation and mechanism of spontaneous periodic modulations of the nematic director close to the temperature T(NA) of a nematic-to-smectic-A phase transition if the surface alignment slightly differs from a pure homeotropic one. Stripe domains appear in the nematic phase about one degree above T(NA) and persist into the Sm A phase. The instability of the homogeneous state with respect to stripe domains is shown to be related to a very large bend constant which is much larger than the twist and splay elastic constants. The instability mechanism consists of reduction of the highly energetic bend deformation, induced by small surface director tilts, at the expense of a spontaneous periodic splay-twist modulation. Using smallness of the twist-to-bend and splay-to-bend elastic constant ratios, the critical condition of the instability and the modulation period are found analytically. Both the experimentally obtained and theoretically predicted domain period scales very closely to a square root of the cell thickness.

11.
Phys Rev E Stat Nonlin Soft Matter Phys ; 76(1 Pt 1): 011707, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17677471

RESUMEN

An external mechanical torque on colloids immersed in a nematic liquid crystal can induce a Coulomb-like 1/r interaction between them [Lev and Tomchuk, Phys. Rev. E 59, 591 (1999); Lev, ibid. 65, 021709 (2002)]. In this paper we show that the director-mediated Coulomb-like interaction of two colloids is determined by the vectors Gamma perpendicular (1) and Gamma perpendicular (2) of the transverse external torques exerted upon these colloids. We derive the 1/r potential in which the scalar product -(Gamma perpendicular (1) x Gamma perpendicular (2)) of the two torques plays the role of the product of two electrostatic charges. The 1/r interaction is attractive for (Gamma perpendicular (1) x Gamma perpendicular (2))>0 and repulsive for (Gamma perpendicular (1) x Gamma perpendicular (2))<0 ("parallel torques" attract whereas "antiparallel torques" repel each other). The vector of transverse torque determines the two-component "elastic charge" (dyad), which is illustrated by the 1/r2 and 1/r3 terms in the elastic energy (the elastic analogs of the monopole-dipole and dipole-dipole interactions). The general status of the pairwise approach to nematic emulsions is considered in terms of the elastic charge density.

12.
Eur Phys J E Soft Matter ; 23(2): 161-74, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17619815

RESUMEN

The interaction between particle-like sources of the nematic director distortions (e.g., colloids, point defects, macromolecules in nematic emulsions) allows for a useful analogy with the electrostatic multipole interaction between charged bodies. In this paper we develop this analogy to the level corresponding to the charge density and consider the general status of the pairwise approach to the nematic emulsions with finite-size colloids. It is shown that the elastic analog of the surface electric charge density is represented by the two transverse director components on the surface imposing the director distortions. The elastic multipoles of a particle are expressed as integrals over the charge density distribution on this surface. Because of the difference between the scalar electrostatics and vector nematostatics, the number of elastic multipoles of each order is doubled compared to that in the electrostatics: there are two elastic charges, two vectors of dipole moments, two quadrupolar tensors, and so on. The two-component elastic charge is expressed via the vector of external mechanical torque applied on the particle. As a result, the elastic Coulomb-like coupling between two particles is found to be proportional to the scalar product of the two external torques and does not directly depend on the particles' form and anchoring. The real-space Green function method is used to develop the pairwise approach to nematic emulsions and determine its form and restrictions. The pairwise potentials are obtained in the familiar form, but, in contrast to the electrostatics, they describe the interaction between pairs (dyads) of the elastic multipole moments. The multipole moments are shown to be uniquely determined by the single-particle director field, unperturbed by other particles. The pairwise approximation is applicable only in the leading order in the small ratio particle size-to-interparticle distance as the next order contains irreducible three-body terms.


Asunto(s)
Cristales Líquidos/química , Modelos Químicos , Modelos Moleculares , Simulación por Computador , Módulo de Elasticidad , Electricidad Estática
13.
Akush Ginekol (Sofiia) ; 46(9): 27-31, 2007.
Artículo en Búlgaro | MEDLINE | ID: mdl-18642561

RESUMEN

OBJECTIVE: To establish the incidence of cervicovaginal infections in patients with preterm and term deliveries. MATERIALS AND METHODS: 88 pregnancies with no previous detectable risk factors have been included in a retrospective study. 48 patients delivered at term and 40 had delivery between 24 and 37 weeks of gestation. A vaginal swab for bacterial infections and a cervical swab for detection of Chlamydia trachomatis infection, using PCR, have been performed in each case. The vaginal ecosystem has been appreciated according Nungent criteria. RESULTS AND CONCLUSIONS: C. trachomatis has been detected in 5% (2/40) of preterm deliveries and in 2.08% (1/48) of term deliveries. In preterm delivery group bacterial vaginosis has been isolated in 15% (6/40), Enterococcus spp. in12.5% (5/40) and Group B Streptococcus in 12.5% (5/40) of cases. In patients, delivered at term, bacterial vaginosis has been proved in 6.25% (3/48), Enterococcus spp in 8.33% (4/48), Group B Streptococcus in 4.17% (2/48) patients. Significant differences between both groups have been found in GBS and BV (p < 0.05). Although the difference C. trachomatis infection is not significantly higher in preterm delivery group, testing for C. tracomatis, using highly specific methods, along with vaginal swab are recommended as routine tests in pregnancy.


Asunto(s)
Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro/etiología , Cervicitis Uterina/complicaciones , Vaginitis/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Estudios Retrospectivos , Factores de Riesgo , Cervicitis Uterina/microbiología , Vaginitis/microbiología
14.
Proc Natl Acad Sci U S A ; 98(5): 2849-54, 2001 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-11226329

RESUMEN

Allopregnanolone (ALLO), is a brain endogenous neurosteroid that binds with high affinity to gamma-aminobutyric acid type A (GABA(A)) receptors and positively modulates the action of GABA at these receptors. Unlike ALLO, 5alpha-dihydroprogesterone (5alpha-DHP) binds with high affinity to intracellular progesterone receptors that regulate DNA transcription. To investigate the physiological roles of ALLO and 5alpha-DHP synthesized in brain, we have adopted a mouse model involving protracted social isolation. In the frontal cortex of mice, socially isolated for 6 weeks, both neurosteroids were decreased by approximately 50%. After administration of (17beta)-17-(bis-1-methyl amino carbonyl) androstane-3,5-diene-3-carboxylic acid (SKF105,111), an inhibitor of the enzyme (5alpha-reductase Type I and II) that converts progesterone into 5alpha-DHP, the ALLO and 5alpha-DHP content of frontal cortex of both group-housed and socially isolated mice decreased exponentially to 10%-20% of control values in about 30 min. The fractional rate constants (k h(-1)) of ALLO and 5alpha-DHP decline multiplied by the ALLO and 5alpha-DHP concentrations at any given steady-state estimate the rate of synthesis required to maintain that steady state. After 6 weeks of social isolation, ALLO and 5alpha-DHP biosynthesis rates were decreased to 30% of the values calculated in group-housed mice. Moreover, in socially isolated mice, the expression of 5alpha-reductase Type I mRNA and protein was approximately 50% lower than in group-housed mice whereas 3alpha-hydroxysteroid oxidoreductase mRNA expression was equal in the two groups. Protracted social isolation in mice may provide a model to investigate whether 5alpha-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate the action of drugs acting as agonists, partial agonists, or positive allosteric modulators of the benzodiazepine recognition sites expressed by GABA(A) receptors.


Asunto(s)
Encéfalo/metabolismo , Dihidrotestosterona/metabolismo , Pregnanolona/biosíntesis , Aislamiento Social , Animales , Secuencia de Bases , Encéfalo/enzimología , ADN , Masculino , Ratones , Modelos Animales , Datos de Secuencia Molecular , Pregnanolona/química , Pregnanolona/metabolismo
15.
Neuropharmacology ; 39(3): 440-8, 2000 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-10698010

RESUMEN

Allopregnanolone (ALLO), a potent positive-allosteric modulator of the action of GABA at GABA(A) receptors, is synthesized in the brain from progesterone by the sequential action of two enzymes: 5alpha-reductase and 3alpha-hydroxysteroidoxidoreductase. The concentration of ALLO in various parts of the mouse brain varies substantially, from 15 pmol/g in the olfactory bulb, to approximately 6 pmol/g in the frontoparietal cortex, and 2.7 pmol/g in the cerebellum. The systemic administration of 48 micromol/kg of the Type I and Type II 5alpha-reductase inhibitor, (17beta)-17-[bis (1-methylethyl) amino carbonyl)] androsta-3, 5-diene-3-carboxylic acid (SKF 105,111), reduced brain ALLO content by 80-90% in 30 min; the rate constant (k) of ALLO decrease in each brain area can be utilized to establish the rate of ALLO biosynthesis, which is higher in the olfactory bulb (62 pmol/g/h) than in the frontoparietal cortex (24 pmol/g/h) or cerebellum (11 pmol/g/h). The duration of the righting reflex loss elicited by the potent GABA(A) receptor agonist muscimol was reduced in SKF 105,111-treated ALLO-depleted mice. SKF 105,111 treatment had no effect on muscimol metabolism or on brain levels of pregnenolone and progesterone; however, the brain levels of 5alpha-DHP, the precursor of ALLO, were also decreased. Administration of ALLO at a dose of 15 micromol/kg i.p. by itself did not alter the muscimol-induced loss of the righting reflex; but it completely blocked the effect of SKF 105,111. To elucidate the possible molecular mechanism by which a decrease of brain ALLO content can shorten the duration of the righting reflex loss elicited by muscimol, we patch-clamped neocortical pyramidal neurons of mice pretreated with SKF 105,111 or vehicle, and studied the efficiency of muscimol in eliciting Cl- currents. The current amplitude was significantly smaller in neurons from SKF 105,111-treated mice, especially at lower doses (0.1-1 microM) of muscimol, and the muscimol dose-response (0.1-10 microM) relationship displayed cooperativity (nH=1.4). These data suggest that ALLO synthesized in brain plays an important physiological permissive role in the modulation of GABA-gated Cl- channel function.


Asunto(s)
Encéfalo/metabolismo , Pregnanodionas/metabolismo , Pregnanolona/biosíntesis , Receptores de GABA-A/metabolismo , 5-alfa-Dihidroprogesterona , Animales , Encéfalo/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Agonistas del GABA/farmacología , Masculino , Ratones , Muscimol/farmacología , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Receptores de GABA-A/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología
16.
Folia Med (Plovdiv) ; 41(1): 62-5, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10462924

RESUMEN

The frequency rate of echinococcis has recently increased rapidly and so has the number of the relapses of the disease. The aim of the present retrospective study was to summarise our experience in the surgical treatment of secondary and recurrent echinococcosis. We discuss the most effective methods for operative treatment in which the intervention spares organs and combines with further antiparasytic treatment.


Asunto(s)
Equinococosis/cirugía , Animales , Femenino , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
17.
Neuropharmacology ; 38(7): 955-63, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10428414

RESUMEN

Allopregnanolone [3alpha-hydroxy-5alpha-pregnan-20-one] (ALLO), a potent neurosteroid that positively modulates gamma-aminobutyric acid (GABA) action at various GABA(A) receptor subtypes is synthesized in nanomolar concentrations and stored non uniformly in various brain structures of mammals. We have measured brain ALLO content and its precursors by negative ion chemical ionization-mass-spectrometry after purification and separation of the different steroids with HPLC and gas chromatography. Our procedure measures steroids in the femtomolar range with structural information and unsurpassed selectivity. We were able to establish an association between the decrease in content of ALLO in mouse brain cortex elicited by either long-lasting social isolation or by the administration of 17beta-17 [bis (1-methylethyl) amino carbonyl] androstane-3,5-dilene-3-carboxylic acid (SKF 105111). an inhibitor of Types I and II 5alpha reductases, and the shortening of the righting reflex loss elicited by pentobarbital (PBT). SKF 105111 added to cortical brain slices in concentrations up to 10(-5) M failed per se to alter GABAergic currents or their potentiation by PTB recorded from pyramidal neurons. Fluoxetine (1.45 or 2.9 micromol/kg i.p.) doses that fail to change the PTB-induced loss of righting reflex and the level of brain ALLO in group-housed mice normalized both parameters in socially-isolated mice. In addition, we could detect both fluoxetine actions in socially isolated mice pretreated with doses of p-chlorophenylalanine (1.2 mmol/kg i.p. at 72, 48, and 24 h) that substantially inhibit brain serotonin 5HT synthesis as shown by an 80% drop of brain 5HT content. These studies for the first time have provided evidence suggesting that the endogenous cortical stores of ALLO physiologically upregulate GABAergic tone and by such a mechanism play a permissive or facilitatory role on the PTB-induced loss of the righting reflex. In the absence of such a permissive physiological influence by endogenous ALLO, the righting reflex inhibition by PTB is down regulated.


Asunto(s)
Pentobarbital/farmacología , Pregnanolona/metabolismo , Reflejo Anormal/efectos de los fármacos , Inhibidores de 5-alfa-Reductasa , Animales , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Masculino , Ratones , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Reflejo Anormal/fisiología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico
18.
Proc Natl Acad Sci U S A ; 95(6): 3239-44, 1998 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-9501247

RESUMEN

We recently reported that fluoxetine or paroxetine, two selective serotonin reuptake inhibitors (SSRIs), when administered to rats, increase the brain content of the neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha5alpha-ALLO) without altering the brain content of other neurosteroids. ALLO (3alpha5alpha and 3alpha5beta isomers) binds with high affinity to various gamma-aminobutyric acid (GABA) receptor A subtypes and facilitates the action of GABA at these receptors. We hypothesized that the increase of ALLO brain content induced by treatment with SSRIs could contribute to alleviating the anxiety and dysphoria associated with the symptomatology of major unipolar depression. We measured ALLO content in four cisternal-lumbar fractions of cerebrospinal fluid (CSF) before and 8-10 weeks after treatment with fluoxetine or fluvoxamine in 15 patients with unipolar major depression. The concentration of ALLO ( approximately 40 fmol/ml in each CSF fraction of three control subjects) was about 60% lower in patients with major unipolar depression. However, in the same patients, fluoxetine or fluvoxamine treatment normalized the CSF ALLO content. Moreover, a statistically significant correlation (r = 0.58; P < 0.023; n = 15) existed between symptomatology improvement (Hamilton Rating Scale for Depression scores) and the increase in CSF ALLO after fluoxetine or fluvoxamine treatment. The CSF content of PREG and PROG remained unaltered after treatment and failed to correlate with the SSRI-induced increase of CSF ALLO. The normalization of CSF ALLO content in depressed patients appears to be sufficient to mediate the anxiolytic and antidysphoric actions of fluoxetine or fluvoxamine via its positive allosteric modulation of GABA type A receptors.


Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Fluoxetina/uso terapéutico , Fluvoxamina/uso terapéutico , Pregnanolona/líquido cefalorraquídeo , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Trastorno Depresivo Mayor/líquido cefalorraquídeo , Trastorno Depresivo Mayor/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Estereoisomerismo
19.
Mutagenesis ; 11(1): 119-23, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8671726

RESUMEN

The clastogenic ability of the restriction endonucleases (MspI, HpaII and HaeIII) in germinating seeds of reconstructed barley karyotype was assessed. An effective induction of chromosomal aberrations after restrictase treatment was observed. The frequency, types and cell-cycle dependence of the observed abnormalities are discussed in relation to the distinct characteristics of the enzymes and the features of the plant genome. The capacity to induce aberrations was not significantly influenced by the nature of the double-strand breaks (blunt- or cohesive-ended); however, it was dependent on the methylation status of the plant DNA. The restriction enzymes displayed an S-independent mode of action revealing the transition between G1 and S as the most sensitive stage of the cell cycle in barley for induction of chromosomal damage.


Asunto(s)
Aberraciones Cromosómicas , Enzimas de Restricción del ADN/toxicidad , Hordeum/efectos de los fármacos , Hordeum/genética , Mutágenos/toxicidad , Secuencia de Bases , Ciclo Celular , Cromosomas/efectos de los fármacos , Cromosomas/ultraestructura , Daño del ADN , ADN de Plantas/efectos de los fármacos , ADN de Plantas/genética , ADN de Plantas/metabolismo , Desoxirribonucleasa HpaII/toxicidad , Desoxirribonucleasas de Localización Especificada Tipo II/toxicidad , Hordeum/citología , Metilación
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