Time-dependent effects of ovarian steroids on tyrosine hydroxylase activity in the limbic forebrain of female rats

Summary In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats.     

Melatonin modifies the spontaneous multiunit activity recorded in several brain nuclei of freely behaving rats.

Melatonin, a pineal hormone, released photoperiodically, was administered systemically in rats, previously implanted with semimicroelectrodes into six different brain structures. The multiunit electrical activity of these structures was recorded for 10 min before and 60 min after melatonin administration in unanesthetized, freely moving rats. Different melatonin doses (100, 200, 500, and 1000 micrograms/kg) produced changes in the electrical activity of all tested structures. However, amygdala, rostral hypothalamus and mesencephalic reticular formation showed the most important changes. The main effect induced by melatonin was a dose-related decrease of the spontaneous electrical activity. The significance of these effects is discussed within the context of the behavioral and endocrinological effects of melatonin.     

Leading etiologic factors in periventricular bleeding and periventricular leukomalacia

Prenatal, intrapartum and postnatal factors were investigated in less than 32 gestational age preterm infants known to have periventricular haemorrhage or periventricular leukomalacia. The diagnoses were established on cranial ultrasonography and/or autopsy. Factors associated with periventricular haemorrhage were: postnatal severe hypercapnia, acidosis and hypoxia. In the periventricular leukomalacia group the incidence of antepartum and intrapartum hypoxia and/or ischaemia (antepartum haemorrhage) were significantly higher than in the control group.     

Cytophotometric investigations on atypical epithelial cells of the human seminal vesicle

Normal seminal vesicles were studied histologically in 80, and by Feulgen’s cytophotometric method in 10 autopsied cases (males, 44–82 years of age). In every case large, hyperchromatic nuclei were found. By cytophotometry euploid polyploid atypia was also shown in every case, which is characteristic of benign hormonal dysplasia.     

Adenocarcinoma cervicis uteri. An appraisal of treatment results for a period of 40 years

A retrospective study was done in 316 patients with primary cervical adenocarcinoma treated at the Research Institute for Clinical and Experimental Oncology in Brno over a period of 40 years (1939-1978). The treatment results were compared to those in 2571 patients with epidermoid carcinomas of the uterine cervix treated at the Institute over the same period. The 5-year survival rate was significantly lower in adenocarcinoma patients (in Stage I patients, 77.8% vs. 84.5%, and, in the whole group, 60.8% vs. 70.3%). The assessment of the treatment results of this study has clearly showed that in cervical adenocarcinomas, surgery combined with radiotherapy was much more effective than radical radiotherapy alone (77.4% vs. 64.7%). In contrast to this, in epidermoid carcinomas the treatment results were better after radical radiotherapy (86.5% vs. 81.3%). Thus, in the prognosis of cervical adenocarcinomas the mass of the tumor, the size of the uterus, as well as the grading play a role. That means that primary cervical adenocarcinomas at early stages can be successfully treated by a combination of radical surgery and radiotherapy, while radiotherapy of advanced stages of this tumor is less successful.     

Dexamethasone inhibits food intake suppression induced by low doses of interleukin-1 beta administered intracerebroventricularly.

Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1 beta (rhIL-1 beta, 0.125 to 2.0 ng/rat) dose-dependently suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. ICV infusion of bovine serum albumin (BSA), or heat-treated rhIL-1 beta had no effect on food intake. Pretreatment with dexamethasone (200 micrograms/rat, intraperitoneal) blocked the food intake suppression induced by low doses of rhIL-1 beta. This ability of dexamethasone, a synthetic corticosteroid, may have potential therapeutic implications in acute and chronic pathological processes associated with increased levels of IL-1 and appetite suppression.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.