Ana C. Barceló

Effects of estrogens and progesterone upon the biosynthesis of melatonin by the pineal gland

Da die Aktivität der Pinealdrüse bei weiblichen Ratten mit dem Cyklus wechselt, wurde die Wirkung von Oe tradiol und Progesteron auf ihre Aktivität bei kastrierten weiblichen Ratten untersucht. Oestradiol bewirkte Gewichtsabnahme und Funktionssteigerung, während Progesteron die Pinealis-Aktivität herabsetzte.

The synovial fluid hyaluronic acid in rheumatoid arthritis

The intrinsic viscosity of hyaluronic acid in synovial fluid decreases significatively in mild and severe arthritis (24% and 37% respectively). Variation in hyaluronic acid concentration parallels the above results. Chondroitin-6-sulfate can be detected in about 30% of the arthritic fluids.

Striatal modulation of the jaw opening reflex

The effect of striatal electrical and chemical conditioning stimulation (L-glutamate 80-160 nmoles/0.5 microl) on the jaw opening reflex (JOR) was studied in Sprague-Dawley male rats anesthetized with urethane. The JOR was evoked by stimulation of the tooth pulp of lower incisors. This response was suppressed by transection of the dental root, which indicates according with the bibliography, a specific activation of the pulp nerves. Three type of responses were obtained on the evoked JOR by conditioning stimulation of the striatum; being the main one the suppression of the reflex elicited by tooth pulp activation. A second type of response was an increase of the tooth-JOR amplitude. This effect was observed more frequently with glutamate stimulation rather than with electrical activation of the striatum. A third response was observed with chemical stimulation but not by electrical stimulation of the striatum. This was a triphasic response which consisted in an increase followed by an inhibition and a late increase of the tooth-JOR amplitude. A biphasic effect, an increase prior to a decrease of the JOR amplitude, was also recorded with a minor frequency. The distribution of effective sites for electrical and chemical stimulation within the striatum are mainly similar located in the rostral aspect of the nucleus, with the inhibitory sites in the middle of the nucleus and intermingled with the excitatory ones. The complex responses (tri/biphasic) were observed ventrally and caudally in the nucleus. On the basis of the results mentioned above, one could assume that the striatum is related to the modulation of the JOR evoked probably by nociceptive stimulation. However, activation of other type of fibers could not be ruled out.

Erythropoietin improves cardiac contractility in post-hypoxic mice

Summary. Mice myocardia, in which plasma erythropoietin (EPO) concentrations were modified in response to different experimental conditions, were studied to evaluate contractility (dF/dt). CF1 mice were randomly separated into four main groups: group I, normocythaemic normoxic; group II‐a, normocythaemic intermittently exposed to hypobaria for 72 h; group II‐b, normocythaemic intermittently exposed to hypobaria for 3 weeks; group III, hypertransfused polycythaemic exposed to 72 h hypobaria; and group IV, hypertransfused polycythaemic maintained in normobaric air. Plasma EPO, contractile studies and binding assays were performed. The dF/dt was significantly higher in group II‐a than in group I and group II‐b; but in groups III and IV, the dF/dt was reduced. The toxic action of ouabain was reduced and delayed in its onset, accompanied by increased numbers of 3H‐ouabain binding sites in group II‐a. Contractility was positively correlated with plasma EPO (pEPO) in the different groups. Treating group I with recombinant human (rHu)‐EPO enhanced contractility while treating group II‐a with a monoclonal anti‐EPO decreased the dF/dt. The inhibition of enzymatic pathway(s) known to participate in the cytokines signal transduction, decreased the basal dF/dt values on atria from group II‐a and on group I atria treated with rHu‐EPO. The results demonstrated: (1) a cardiac non‐haematopoietic effect of EPO; (2) that mice in which the pEPO concentration increased showed improvement in contractility and in the therapeutic action of ouabain; and (3) it is possible that EPO may act as a cardioprotective agent by modulating the cardiac Na+–K+ pump.

Erythropoietin formation during hypoxia in mice with impaired responsiveness to erythropoietin induced by irradiation or 5-fluorouracil injection

Plasma erythropoietin levels during continuous exposure to hypobaric hypoxia in mice with marrow aplasia induced by whole body X-irradiation or 5-fluorouracil injection were higher than in control mice similarly exposed. These findings give support to the hypothesis that a relationship exists between erythropoietin production rate and erythroid responsiveness to the hormone.

The Concentration of Dietary Casein Required for Normal Mandibular Growth in the Rat

To determine a suitable casein concentration for normal, undeformed mandibular growth, we placed weanling male rats on diets containing graded levels of casein between 0% and 30% for 19 days. Some weanlings were killed so that initial values could be established. Ten linear dimensions corresponding to the six skeletal units of the mandible were evaluated so that their growth rates at the end of the experimental period could be established. Other dimensions were also evaluated for study of the growth rate of the bone as a whole. The macroscopic growth of the mandible showed a sigmoidal relationship with dietary casein concentration, most of the measurements reaching a plateau at 20% casein. Within the skeletal units, four dimensions corresponding to the alveolar and symphyseal regions did not change with age and were not affected by the casein content of the diet. The remaining six dimensions-corresponding to condylar, coronoid, angular, and basal regions of the mandible-increased with age and were related positively to dietary casein concentration. Their growth patterns were not uniform, although all of them reached maximal values when the diet contained 20% casein. Therefore, deformation of the mandible appears to occur in rats fed diets with a casein concentration lower than 20%. It appears that a dietary casein concentration of 20% is required for normal, undeformed mandibular growth.

The Striatum and Pain Modulation

The aim of this review was to give a general aspect of the sensorial function of the striatum related to pain modulation, which was intensively studied in our laboratory. We analyse the effect of electrical and chemical stimulation of the striatum on the orofacial pain, especially that produced by tooth pulp stimulation of the lower incisors. We demonstrated specific sites within the nucleus which electrical or chemical stimulation produced inhibition of the nociceptive jaw opening reflex. This analgesic action of the striatum was mediated by activation of its dopamine D2 receptors and transmitted through the indirect pathways of the basal ganglia and the medullary dorsal reticular nucleus (RVM) to the sensorial nuclei of the trigeminal nerve. Its mechanism of action was by inhibition of the nociceptive response of the second order neurons of the nucleus caudalis of the V par.

Effect of electrical and chemical stimulation of the subthalamic nucleus on the release of striatal dopamine.

High‐frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinsons disease, but the mechanisms underlying these clinical results remain to be clarified. The HFS of STN is associated with the release of dopamine (DA) in the striatum. This study examines possible mechanisms by which HFS–STN release DA. The experiments were performed in rats anesthetized with urethane. The STN was stimulated by electrical HF and chemical microinjections of an antagonist and an agonist of GABAA receptors, the bicuculline, and the muscimol, respectively. The extracellular striatal DA‐DOPAC (3‐4‐dihydroxyphenilacetic acid) content was collected by means of intracerebral microdialysis cannula and analyzed with HPLC with an electrochemical detector. The HFS of STN and microinjection of bicuculline intrasubthalamic produced a significant increase of extracellular striatal DA, whereas DOPAC levels were unchanged. The microinjection of muscimol depresses spontaneous release of DA, without changes in DOPAC. The kainic acid lesion of the globus pallidus (GP) and the substantia nigra pars reticulata (SNr), ipsilateral to dialyzed striatum, did not modify the release of DA‐DOPAC. These data provide evidence that the STN has a tonic action on the substantia nigra pars compacta (SNc), and the release of striatal DA by HFS–STN may be due to activation of the STN acting directly on SNc neurons. Synapse 64:905–915, 2010. VVC 2010 Wiley‐Liss, Inc.

Study of the neural basis of striatal modulation of the jaw-opening reflex

Previous experimental data from this laboratory demonstrated the participation of the striatum and dopaminergic pathways in central nociceptive processing. The objective of this study was to examine the possible pathways and neural structures associated with the analgesic action of the striatum. The experiments were carried out in rats anesthetized with urethane. The jaw-opening reflex (JOR) was evoked by electrical stimulation of the tooth pulp of lower incisors and recorded in the anterior belly of the digastric muscles. Intrastriatal microinjection of apomorphine, a nonspecific dopamine agonist, reduced or abolished the JOR amplitude. Electrolytic or kainic acid lesions, unilateral to the apomorphine-injected striatum, of the globus pallidus, substantia nigra pars reticulata, subthalamic nucleus and bilateral lesion the rostroventromedial medulla (RVM), blocked the inhibition of the JOR by striatal stimulation. These findings suggest that the main output nuclei of the striatum and the RVM may be critical elements in the neural pathways mediating the inhibition of the reflex response, evoked in jaw muscles by noxious stimulation of dental pulp.

Androgens and Erythropoiesis. Induction of Erythropoietin- Hypersecretory State and Effect of Finasteride on Erythropoietin Secretion

The major activity of androgens in promoting erythropoiesis is mediated by the ability of these steroids to increase erythropoietin (EPO) production. Testosterone exerts a nephrotrophic action which is evidenced by an increased renal mass following chronic administration of this steroid. The increased renal mass, in turn, may be associated with an increased capacity for production of EPO by the organ. The present study was thus designed to test the hypothesis that chronic administration of testosterone induces an EPO-hypersecretory state (EPO-HS) defined as a condition of higher than normal EPO synthesis and secretion in response to well-known erythropoietic stimuli, such as hypoxia, anaemia or cobalt. In addition, since 5α-dehydrotestosterone (5α-DHT) was found to be more active than testosterone in stimulating EPO production, the effect of inhibition of the 5α-reductase by finasteride on both constitutive and stimulated EPO secretion was also estimated. Female adult mice receiving 2 mg testosterone propionate three times a week for 3.5 weeks increased their erythrocyte production rates at day 4 and at the time of each sampling points thereafter during the injection period. Average renal weight was about 1.8 times higher in testosterone-treated than in vehicle-treated mice. When mice were hypertransfused at the end of the injection period and exposed to hypobaric air, both RBC-59Fe uptake and plasma EPO concentration (pEPO) were several times greater in androgen-treated than in vehicle-injected mice. No changes were observed in both parameters under normobaric conditions Testosterone treatment altered neither the plasma disappearance (t1/2) of radiolabelled rh-EPO nor the erythropoietic response to exogenously administered rh-EPO. pEPO was similar into normoxic male and female mice and neither orchidectomy nor finasteride (10 mg/kg/day for 12 days) modified these levels. Significant differences were seen in pEPO levels between male and female mice under hypoxic conditions. Orchidectomy and finasteride both lowered the hypoxia-dependent increment in pEPO in male mice to levels that were not significantly different from those of hypoxic female mice. In summary, an EPO-HS followed chronic administration of testosterone in mice, which may or may not be related to the nephrotrophic effect of this androgen. Since finasteride adversely affected stimulated-EPO production in mice, it is suggested that the testosterone effect on stimulated-EPO secretion is mediated by DHT. In contrast, the findings of unchanged baseline pEPO in either orchidectomised or finasteride-treated mice suggest that constitutional EPO production is not influenced by testosterone.