Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling.

In primates, including women, and in rodents, natural killer lymphocytes (NK cells) have a unique relationship with the decidualizing uterus. Implantation sites from genetically modified and transplanted mice have proven useful models for understanding potential mechanisms involved in the recruitment, activation and functions of human CD56(bright) uterine (u)NK cells. Key findings are reviewed in this article. In mice, uNK precursor cells are recruited from secondary lymphoid tissues and are activated coincident with their uterine arrival. uNK cells proliferate, produce cytokines (interferon gamma (IFN-gamma) and interleukin 18 (IL-18) and IL-27), and terminally differentiate into granulated lymphocytes. Many uNK cells proliferate within the myometrium at each implantation site forming a structure, the mesometrial lymphoid aggregate of pregnancy (MLAp) that surrounds blood vessels servicing each placenta. Post-mitotic uNK cells are abundant within decidua basalis; frequently (<25%) associating with spiral arteries, intramurally and intraluminally. From mid-gestation, numbers of uNK cells decline. Studies of implantation sites in mice lacking uNK cells, IFN-gamma, components of IFN-gamma-induction and -signalling pathways or IFN-gamma-regulated genes indicate that uNK cell-derived IFN-gamma is essential in triggering pregnancy-induced spiral artery modification. Decidual maintenance and uNK cell death are additional effects of uNK cell-derived IFN-gamma. Thus, during the first half of gestation, uNK cells contribute to and sustain important changes in the maternal placental bed.

Up-regulation of oxytocin receptor messenger ribonucleic acid and protein by estradiol in the cervix of ovariectomized rat.

Oxytocin receptor (OTR) regulation has been extensively studied in uterine myometrium and endometrium. However, studies in the cervix are limited. The present studies utilized in situ hybridization and immunocytochemistry to localize OTR mRNA and protein distribution in cervices of nonpregnant ovariectomized (OVX) rats and examined the effect of combined and independent treatments with estradiol and progesterone on cervical OTR. Thirteen nonpregnant rats were bilaterally OVX under general anesthesia. At least 7 days later, the rats were exposed to one of four different treatments 24 h prior to necropsy: 1) estradiol (50 microg, n = 4); 2) progesterone (10 mg, n = 3); 3) both estradiol (50 microg) and progesterone (10 mg) (n = 3); 4) corn oil vehicle (n = 3). After 24-h estradiol treatment, OTR mRNA increased significantly (p < 0.05) in smooth muscle cells of the rat cervix as a result of increased copy numbers of OTR mRNA per cell as well as an increased population of OTR mRNA-positive cells. Progesterone alone had no effect on OTR mRNA expression; however, progesterone combined with estradiol significantly inhibited the up-regulation of OTR mRNA by estradiol alone. The increase of OTR mRNA in cervical epithelial cells was minimal in all situations. Intensity of cervical OTR immunostaining in both the epithelial cells and cervical smooth muscle cells was also elevated after estradiol treatment. The anti-rat OTR antiserum used for immunocytochemistry was validated by Western blot analysis. In conclusion, OTR and OTR mRNA were localized in smooth muscle cells and in epithelial cells of rat cervix. Estradiol-dependent activation of OTR gene expression and active OTR synthesis in smooth muscle cells account for the increased OTR level in rat cervix in vivo, in which progesterone acted as an antagonist of estradiol on OTR gene expression.

Desenvolvimento de um novo modelo acadêmico na educaçäo dos profissionais de saúde no contexto do Prouni-Londrina (1991-1997): sistematizaçäo e reflexöes teórico-metodológicas / Development of a new academic model in the pedagogical support of health professionals in the Prouni-Londrina context (1991-1997): sistematization and reflexions

Este trabalho consiste na análise e reflexäo das transformaçöes que vêm sendo realizadas nos últimos 6 anos nos cursos do Centro de Ciências da Saúde da Universidade Estadual de Londrina. Em 1991, foram regulamentadas mudanças de regime acadêmico de crédito para seriado, e de currículos, além da seleçäo do CCS para participar do programa UNI. Desde entäo, várias estratégias vem sendo utilizadas com vistas ao novo modelo acadêmico, tais como a implantaçäo de projetos especiais que integram academia, serviços de saúde e comunidade, projetos de apoio ao desenvolvimento de pesquisas integradas ao ensino e à comunidade, criaçäo de estrutura de apoio pedagógico e mudanças na estrutura organizacional, além do processo de aprimoramento e capacitaçäo em novas metodologias, sempre com uma grande participaçäo de docentes, alunos e membros da comunidade. Em vista deste processo de construçäo coletiva, tem início a definiçäo dos projetos pedagógicos dos 5 cursos do CCS, baseados nos problemas relevantes da sociedade, nas tendências internacionais de educaçäo e com estratégias/metodologias de ensino que privilegiam a construçäo do conhecimento. Para a reformulaçäo, aprimoramento e redirecionamento das nossas metas, nos baseamos em pressupostos teóricos da transdisciplinaridade, e na teoria da complexidade, rumo a Pedagogia da Interaçäo

Effect of in vivo estradiol administration to bilaterally ovariectomized rats on in vitro myometrial responsiveness to prostaglandin F2alpha and oxytocin.

Bilaterally ovariectomized, nonpregnant female CD rats were studied to investigate the effect of estradiol treatment on in vitro myometrial responsiveness to oxytocin and prostaglandin F2alpha. The first study investigated dose-dependent effects. Seven days after ovariectomy rats were given a single s.c. dose of corn oil (n = 4) or estradiol (5 microg, n = 5; 15 microg, n = 5; 50 microg, n = 4). A second identical injection of corn oil or estradiol was administered 24 h after the initial injection. Rats were killed 48 h after the first injection. A second study investigated time-dependent effects of estradiol treatment. A second group of ovariectomized rats received s.c. estradiol (50 microg) seven days after ovariectomy. These rats were killed either 12 h (n = 5) or 24 h (n = 4) after injection. Full-thickness cross-sections of uteri were suspended in vitro in the longitudinal direction in a superfusion system. Cumulative concentration-response curves were constructed to oxytocin and prostaglandin F2alpha. Both the duration and dose of estradiol treatment significantly (p < 0.05) attenuated baseline contractile activity, and the maximum myometrial response to oxytocin and prostaglandin F2alpha. Estradiol, in a dose-dependent manner, significantly reduced myometrial sensitivity (p < 0.05) for oxytocin and prostaglandin F2alpha.

Insuficiencia renal aguda pos-transplante renal. / Acute renal failure after kidney transplantation

Dentre 114 pacientes submetidos a transplante renal, os autores observaram a ocorrencia de disfuncao renal pos-operatoria do tipo necrose tubular aguda em 16% dos receptores de rim de doador vivo aparentado e em 50% dos casos em que o doador era descerebrado. A hemodialise pos-operatoria, 3 vezes por semana, com heparinizacao continua na dose de 10 unidades/ kg/hora, nao aumentou a morbidade, enquanto permitiu aguardar-se a recuperacao de diurese adequada, de sorte que a funcao renal, medida pela creatinina plasmatica, estava igual a do grupo sem insuficiencia renal, exceto nos poucos casos de necrose tubular aguda observados quando o doador era vivo e aparentado. Ao final do primeiro ano de observacao houve maior perda renal por agressao imunologica irreversivel naqueles pacientes que tiveram insuficiencia renal aguda

Kidney transplantation: the use of abnormal kidneys.

We transplanted 6 anatomically abnormal kidneys: a horseshoe kidney that after division was transplanted into 2 recipients; 1 kidney with ureteral stones and hydronephrosis; 1 ectopic and 1 hydronephrotic kidney; 2 kidneys with extensive ureteric lesions, donated as free organs. All these kidneys ultimately had normal function in the recipients, long-term in 4.2 patients died but in neither was the death caused by the renal abnormality.

Anestesia em pacientes com insuficiencia renal e uremia. / Anesthesia in patients with renal failure and uremia

Estudamos, retrospectivamente, 52 pacientes uremicos, por insufuciencia renal cronica, submetidos a 102 anestesias para cirurgias de grande porte (duracao media 195.5 +/- 76,3 minutos), analisando e comparado as alteracoes da potassemia durante diferentes tecnicas anestesicas. Hemodialise foi realizada 12 horas antes da cirurgia, exceto quando os pacientes eram admitidos para transplante de rim de cadaver, nos quais o objetivo era corrigir as alteracoes de azotemia e obter, com transfusao de hemacias, valores de hematocritos em torno de 25% (X = 27.0; DP 6,6); o potassio serico que antecedeu a cirurgia foi de 4.6 =/- 0,9 mEq/1. A associacao anestesica mais comumente empregada foi halotano, succinilcolina venosa continua (63% dos casos), seguindo-se a adicao de oxido nitroso e succinilcolina venosa continua.Nao houve obito anestesico apesar de duas paradas cardiacas e dos tres episodios de insuficiencia respiratoria imediata, que foram de curta duracao e de recuperacao espontanea. Ocasionalmente, a potassemia pos-operatoria imediata aumentou de 1.4 mEq/1, porem, em media, as alteracoes nao foram significativas e nao tiveram correlacao com as paradas cardiacas observadas

[Effect of furosemide, potassium canrenoate and D-L-propranolol on blood pressure in spontaneously hypertensive rat]. / Effets du furosémide, du canrénoate de potassium et du D-L-propranolol sur la pression artérielle des rats spontanément hypertendus de souche japonaise

Spontaneously hypertensive rats (japanese strain) have been treated with furosemide, potassium canrenoate or d-l-propranolol. Present results indicate that: 1)furosemide admiinistration, from the 3rd to the 15th week of life, does not prevent the development of hypertension but the blood pressure rises more slowly in treated rats. In the established phase of hypertension furosemide administration produces a decrease in blood pressure; the blood pressure increases rapidly after cessation of the treatment. 2) potassium canrenoate, injected from the 3rd to the 14th week of life, does not prevent the rise in blood pressure.3) d-l-propranolol, administered from the 5th to the 34th week of life, is without effect on the development of hypertension, though it significantly decreases heart rate.