RESUMO
Seminal plasma is not just a spermatozoa carrier. It induces the expression of inflammatory cytokines and chemokines and a massive infiltration of neutrophils, monocytes and dendritic cells in the female genital mucosa after coitus, enabling the innate immune system to fight against sexually transmitted pathogens. However, exposure to seminal plasma not only turns on an inflammatory response but also induces regulatory mechanisms that allow the fetus (a semiallograft) to grow and develop in the uterus. In mouse models it has been shown that seminal plasma induces the expansion of regulatory T cells specific to seminal Ags in the receptive partner, thus promoting tolerance to paternal alloantigens and avoiding allogeneic fetal rejection. These mechanisms appear to be mainly induced by prostaglandins of the E series (PGE) and TGF-ß, which are present at huge concentrations in the seminal plasma. Moreover, we have recently shown that exposure to seminal plasma induces the differentiation of dendritic cells into a tolerogenic profile through a mechanism dependent on the activation of the prostanoid receptors EP2 and EP4 by seminal PGE. Our hypothesis proposes that this tolerogenic response induced by seminal PGE, while promoting fertility by inducing tolerance toward paternal alloantigens, might also compromise the development of the adaptive immune response against sexually transmitted pathogens in the receptive partner.
Assuntos
Tolerância Imunológica/imunologia , Modelos Imunológicos , Prostaglandinas E/imunologia , Sêmen/química , Infecções Sexualmente Transmissíveis/imunologia , Linfócitos T Reguladores/imunologia , Animais , Células Dendríticas/imunologia , Feminino , Masculino , Camundongos , Prostaglandinas E/análiseRESUMO
We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9+/-1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mare's serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E(2)) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E(2) and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F(2alpha) (PGF(2alpha)) or PGE by ovaries with functional CL, whereas DHEA decreased PGF(2alpha) and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E(2) levels from mice with ovaries with functional CL and serum P, PGF(2alpha) and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E(2) levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/(*)OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.
Assuntos
Corpo Lúteo/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Metformina/farmacologia , Animais , Corpo Lúteo/fisiologia , Dinoprosta/análise , Dinoprosta/metabolismo , Feminino , Hiperandrogenismo/patologia , Hiperandrogenismo/fisiopatologia , Hipoglicemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Ovário/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Gravidez , Prostaglandinas E/análise , Prostaglandinas E/metabolismoRESUMO
The purpose of the present report was to study the possible relationship between ovarian functionality and the immune response during cystogenesis induced by androgenization with dehydroepiandrosterone (DHEA). Daily injection of DHEA (6 mg/kg body weight) for 20 consecutive days induced ovarian cysts in BALB/c mice. As markers of ovarian function, serum estradiol (E) and progesterone (P) and the ovarian inmunomodulator prostaglandin E (PGE) were analyzed. In order to know how the integrity of the tissue was altered after induction of cystogenesis, the oxidative status was also evaluated. Serum E and P levels, and ovarian PGE concentration, were increased in animals with cysts compared with healthy controls. The oxidant status (quantified by malondialdehyde (MDA) formed after the breakdown of the cellular membrane by free radical mechanisms) was augmented, meanwhile the antioxidant (evaluated by the glutathione (GSH) content) diminished during the induction of cystogenesis. Both immunohistochemical and flow cytometry assays demonstrated that DHEA treatment increased the number of T lymphocytes infiltrating ovarian tissue. Therefore, while ovarian controls showed equivalent expression of CD4+ and CD8+ T cell subsets, injection of DHEA yielded a selective ovarian T cell infiltration as demonstrated by enhanced CD8+ and diminished CD4+ T lymphocyte expression. These results show that the development of cysts involves changes in ovarian function and an imbalance in the oxidant-antioxidant equilibrium. We observed also both an increased and selective T lymphocyte infiltration.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Cistos Ovarianos/imunologia , Ovário/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos BALB C , Cistos Ovarianos/sangue , Cistos Ovarianos/induzido quimicamente , Ovário/química , Ovário/patologia , Oxirredução , Estresse Oxidativo/imunologia , Prostaglandinas E/análiseRESUMO
The phospholipase A2 activity in young amniotic fluids: 1.782, was determined. In the term amniotic fluids, the activity was 10.693. The detected activity in fluids from premature rupture of membranes was 29.077 in the group with infection, add 12.357 for the samples without infection. It was seen that young amniotic fluid has less activity. The group with infection showed the greatest activity. The significant increase of phospholipase A2 activity in term amniotic fluids and with PRM, in comparison with what is seen in young fluids suggests the active participation of the soluble form of this enzyme as mediator in the increase of Prostaglandin E2 seen in the amniotic fluid of the two first groups. Accordingly, one may think that PPLA2 could be a central mediator in membranes rupture mechanism in normal labor, as in PRM.
Assuntos
Ruptura Prematura de Membranas Fetais/enzimologia , Fosfolipases A/análise , Complicações Infecciosas na Gravidez/enzimologia , Líquido Amniótico/enzimologia , Feminino , Humanos , Fosfolipases A2 , Gravidez , Primeiro Trimestre da Gravidez , Prostaglandinas E/análiseRESUMO
The effects of progesterone (P4) and of calcium-ionophore A-23187, on the release of prostaglandins (PGs) E2 and F2 alpha, in uteri isolated from ovariectomized rats and the influences of mepacrine and nifedipine, were explored. The metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF 1 alpha, PGE 2 and PGF2 alpha) in uterine segments from spayed rats, injected or not with P4, was also studied. In all cases ovariectomy was performed 20-25 days prior to sacrifice. One group of spayed rats were injected with 4.0 mg of P4 during two days and sacrificed 24 h after the last injection. The remaining spayed animals were considered as controls. Tissue samples from both groups were incubated for one hour in the absence or in the presence of either A-23187 (1.0 microgram/ml), mepacrine (10(-3) M) or nifedipine (10(-6) M), or a combination of A-23187 plus mepacrine. At the end of the incubating period PGs in the suspending solution were extracted, separated, identified (TLC) and quantitated. The metabolism of 14C-AA into different prostanoids was explored in uterine segments from spayed rats, injected or not with P4 prior to sacrifice. Tissue prepared from P4-injected rats as well as those from rats not receiving P4 but incubated with ionophore A-23187, generated and released significantly more PGF2 alpha into the incubating solution than basal controls, but failed to exhibit changes in the basal output of PGE.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Dinoprosta/análise , Progesterona/farmacologia , Prostaglandinas E/análise , Útero/efeitos dos fármacos , Animais , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Calcimicina/farmacologia , Feminino , Nifedipino/farmacologia , Ovariectomia , Quinacrina/farmacologia , Ratos , Ratos Endogâmicos , Útero/metabolismoAssuntos
Artrite Reumatoide/fisiopatologia , Propionatos/farmacologia , Líquido Sinovial/efeitos dos fármacos , Fosfatase Ácida/análise , Adulto , Artrite Reumatoide/tratamento farmacológico , Ensaios Clínicos como Assunto , Feminino , Humanos , L-Lactato Desidrogenase/análise , Masculino , Prostaglandinas E/análise , Prostaglandinas F/análise , Líquido Sinovial/análise , Líquido Sinovial/citologiaRESUMO
El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5§ día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento
Assuntos
Adulto , Humanos , Masculino , Feminino , Artrite Reumatoide/fisiopatologia , Propionatos/farmacologia , Líquido Sinovial/efeitos dos fármacos , Fosfatase Ácida/análise , Ensaios Clínicos como Assunto , L-Lactato Desidrogenase/análise , Prostaglandinas E/análise , Prostaglandinas F/análise , Líquido Sinovial/análise , Líquido Sinovial/citologiaRESUMO
El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5º día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento (AU)
Assuntos
Adulto , Humanos , Masculino , Feminino , Artrite Reumatoide/fisiopatologia , Propionatos/farmacologia , Líquido Sinovial/efeitos dos fármacos , Fosfatase Ácida/análise , Ensaios Clínicos como Assunto , L-Lactato Desidrogenase/análise , Prostaglandinas E/análise , Prostaglandinas F/análise , Líquido Sinovial/análise , Líquido Sinovial/citologiaAssuntos
Hidróxido de Alumínio/farmacologia , Antiulcerosos , Bismuto/farmacologia , Duodeno/análise , Mucosa Gástrica/análise , Compostos Organometálicos , Prostaglandinas E/análise , Adulto , Hidróxido de Alumínio/uso terapêutico , Antiulcerosos/uso terapêutico , Bismuto/uso terapêutico , Ensaios Clínicos como Assunto , Dinoprostona , Método Duplo-Cego , Úlcera Duodenal/tratamento farmacológico , Feminino , Ácido Gástrico/metabolismo , Humanos , Mucosa Intestinal/análise , Masculino , Pessoa de Meia-IdadeRESUMO
We used pregnant sheep and their fetuses as well as newborn lambs (with and without severe respiratory distress due to prematurity) to study the differences in plasma clearance rate, production rate, and circulating concentrations of immunoreactive PGE2. Fetal PGE2 concentrations were significantly higher than simultaneous maternal concentrations. After delivery by cesarean section, all newborn animals were paralyzed and mechanically ventilated. The PGE2 concentrations fell in those lambs that required only minimal ventilatory support (FIO2 < 0.25) and were similar to maternal concentrations by two to three hours. Newborn lambs that developed severe respiratory distress (FIO2 < 0.55) continued to have concentrations that were even greater than fetal concentrations. The elevated PGE2 concentrations in severely distressed lambs were due not only to a decreased plasma clearance rate but also to an increased production rate of PGE2. Since PGE2 appears to maintain the patency of the ductus arteriosus in the fetus and preterm neonate, we examined the patency of the ductus arteriosus in 3-hour-old newborn lambs by radioactive microsphere injections. The ductus was more widely patent in lambs with higher concentrations of PGE2. The increased circulating concentrations of PGE2 in newborn lambs with severe respiratory distress may contribute to the pathogenesis of patent ductus arteriosus by exerting an additional vasodilatory effect on the vessel.
Assuntos
Permeabilidade do Canal Arterial/sangue , Sangue Fetal/análise , Prostaglandinas E/análise , Animais , Animais Recém-Nascidos/sangue , Permeabilidade do Canal Arterial/complicações , Feminino , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Síndrome do Desconforto Respiratório do Recém-Nascido/sangue , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , OvinosRESUMO
The level of PGE is increased 10-fold in intestinal tissues during primary infection of the rat with Nippostrongylus brasiliensis. Peak levels (ca. 7,000 pg/cm) were assayed in the jejunal site of infection on day 7 of infection and similar levels were recorded in 'post-infection' (ileal) segments at this time. The level of PGE in 'post-infection' segments showed further increase to 12,000 pg/cm on day 10. The level of PGE also increased in 'pre-infection' (duodenal) but this was delayed by 4-5 days. The level of PGF also increased during primary infection (from about 100 to 950 pg/cm) but this occurred after expulsion. Increase in the level of PGE occurred earlier (at 3-4 days) during secondary challenge given 19 days after primary infection, but the PGE levels followed the primary response when challenge was given 10 weeks after primary infection. It is suggested that PGE plays a dual role in parasite immunity. (1) PGE may directly affect metabolism of the parasite. In this event it is also suggested that protective antibodies cause the release of PG. (2) Elevated levels of PGE act indirectly by affecting gastrointestinal function which alters the microenvironment at the site of infection. The duodenal migration of parasites may be due to this effect of PGE.