Effects of in vitro, acute and chronic treatment with fluoxetine on the sympathetic neurotransmission of rat vas deferens.

It is described that fluoxetine treatment is able to induce ejaculatory disorders. However, the exact mechanism is still not fully understood. Therefore, this study was carried out to further evaluate the anti-ejaculatory effects of fluoxetine, using different approaches (in vitro or in vivo treatments), on the sympathetic neurotransmission of the rat vas deferens. Vas deferens from male Wistar rats were used to check the in vitro effects of fluoxetine 10-6M, 3.10-6M or 10-5M. Animals were also acutely (20mg/kg, i.p. 4h or 24h) or chronically (10mg/kg, i.p., 30days) treated with fluoxetine or drug-free vehicle. The vas deferens from non-treated and treated animals were isolated and mounted in an isolated organ bath for the study of the contractions induced by adrenergic agonists, tyramine, 5-HT, Ca2+ or electrical field stimulation. In vitro or acute treatment with fluoxetine decreased the contraction induced by agonists, Ca2+ or electrical field stimulation. The chronic treatment with fluoxetine decreased the contractions induced agonists, tyramine or Ca2+, but did not modify the contractions induced by electrical field stimulation. We have shown that in vitro or in vivo fluoxetine treatment is able to alter the sympathetic neurotransmission of the rat vas deferens which could be related to alterations in the calcium signalling.

Cardiac autonomic balance in rats submitted to protein restriction after weaning.

1. In the present study, we evaluated the autonomic balance of the heart in protein/energy-undernourished rats. 2. Rats were divided into two groups according to the diet they received after weaning: (i) the control group (n=16), given a 15% protein diet, and (ii) the malnourished group (n=14), fed a 6% protein diet. Cardiovascular recordings were made and, through selective autonomic blockade, the tonic autonomic balance, cardiac autonomic index and the power spectrum of heart rate (HR) variability were determined. 3. Muscarinic receptor blockade with methylatropine (5.0 mg/kg, i.v.) increased HR in the control group (371 ± 6 vs 427 ± 15 b.p.m. before and after drug administration, respectively), but not the malnourished group (438 ± 24 vs 472 ± 38 b.p.m. before and after drug administration, respectively). Inhibition of ß(1)-adrenoceptors with metoprolol (2.0 mg/kg, i.v.) reduced HR in malnourished rats (428 ± 24 vs 355 ± 16 b.p.m. before and after drug administration, respectively), but had no effect on the HR of the control group (363 ± 8 vs 362 ± 7 b.p.m. before and after drug administration, respectively). Double autonomic blockade by inhibiting both muscarinic cholinoceptors and ß(1)-adrenoceptors reduced HR in the malnourished group (428 ± 24 vs 342 ± 14 b.p.m.) but had no effect on HR in the control group (371 ± 6 vs 382 ± 6 b.p.m.). 4. Sympathetic tone was augmented in malnourished compared with control rats (131 ± 17 vs 41 ± 11 b.p.m., respectively), whereas parasympathetic tone was reduced in malnourished compared with control rats (-4 ± 4 vs 22 ± 9 b.p.m., respectively). 5. The ratio of oscillations in HR induced by sympathetic and parasympathetic activity was higher in malnourished compared with control rats (0.43 ± 0.03 vs 0.34 ± 0.02, respectively). 6. The results of the present study indicate that protein malnutrition after weaning increases sympathetic activity and reduces vagal activity to the heart in rats. These data provide a new perspective on the pathophysiology of metabolic and cardiovascular diseases associated with protein malnutrition, especially with regard to autonomic modulation.

Effect of darkness on upper eyelid position.

PURPOSE: To determine the magnitude of upper eyelid retraction induced by sudden darkness in normal subjects and in patients with Graves upper eyelid retraction before and after treatment with guanethidine drops. METHODS: The study comprised 211 control subjects (n=211 eyes) and 45 patients (n=78 eyes) with Graves upper eyelid retraction. The control subjects were divided in four age groups: 0 to 1 year, 2 to 9 years, 0 to 18 years, and 19 to 61 years. Twenty-one patients with Graves upper eyelid retraction (n=39 eyes) used guanethidine drops for 15 days. Palpebral fissure images of subjects were acquired in photopic conditions and in darkness. For both images, the distance between the mid-pupil and upper eyelid margin was measured. RESULTS: Darkness induced upper eyelid retraction in all subjects. The increment in the mid-pupil eyelid distance was greater in children. There was no significant difference between the magnitude of eyelid elevation of Graves patients and normal adults. Guanethidine drops did not abolish the eyelid reflex in Graves patients. CONCLUSIONS: Darkness provokes upper eyelid retraction in control subjects and in patients with Graves upper eyelid retraction. This effect decreases with age and does not result from sympathetic stimulation of the Muller muscle.

Protective effects of N-acetylserotonin against 6-hydroxydopamine-induced neurotoxicity.

The present work studied in vivo neuroprotective effects of n-acetylserotonin (NAS), the immediate precursor of melatonin, on the dopaminergic system, in rats lesioned with the unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks after the lesion, the dopamine receptor agonist, apomorphine, produced rotational asymmetry, and the NAS treatment significantly reduced the motor deficit following the apomorphine challenge. The apomorphine-induced rotational behavior was blocked by 84, 86 and 53% after NAS, at doses of 2, 5 and 10 mg/kg, i.p., respectively. The injection of 6-OHDA significantly decreased DA, DOPAC and HVA levels in the rat striatum. In contrast, the NAS (2, 5 and 10 mg/kg, i.p., daily for 7 days) treatment partially reversed the decreases caused by 6-OHDA, and the neurotransmitter levels were brought to approximately 50% of that observed in the contralateral sides. NAS was more efficient at the smaller doses. NAS (5 mg/kg) produced an up-regulation of D1 (37%) and D2 (37%) receptors associated with a decrease in Kd values.

Central alpha(2) adrenergic receptors and cholinergic-induced salivation in rats.

Salivation induced by intraperitoneal (i.p.) injections of pilocarpine (cholinergic agonist) is reduced by intracerebroventricular (i.c.v.) injections of moxonidine (alpha(2) adrenergic and imidazoline receptor agonist). In the present study, we investigated the involvement of central alpha(2) adrenergic receptors in the inhibitory effect of i.c.v. moxonidine on i.p. pilocarpine-induced salivation. Male Holtzman rats with stainless steel cannula implanted into the lateral ventricle (LV) were used. Saliva was collected using pre-weighted small cotton balls inserted into the animal's mouth under ketamine (100 mg x kg(-1)) anesthesia. Salivation was induced by i.p. injection of pilocarpine (4 micromol x kg(-1)). Pilocarpine-induced salivation was reduced by i.c.v. injection of moxonidine (10 nmol) and enhanced by i.c.v. injections of either RX 821002 (160 nmol) or yohimbine (320 nmol). The inhibitory effect of i.c.v. moxonidine on pilocarpine-induced salivation was abolished by prior i.c.v. injections of the alpha(2) adrenergic receptor antagonists, RX 821002 (160 nmol) or yohimbine (160 and 320 nmol). The alpha(1) adrenergic receptor antagonist prazosin (320 nmol) injected i.c.v. did not change the effect of moxonidine on pilocarpine-induced salivation. The results suggest that moxonidine acts on central alpha(2) adrenergic receptors to inhibit pilocarpine-induced salivation, and that this salivation is tonically inhibited by central alpha(2) adrenergic receptors.

Melatonin reverses neurochemical alterations induced by 6-OHDA in rat striatum.

The present work showed that the intrastriatal injection of 6-OHDA significantly decreases DA, DOPAC and HVA levels in that rat brain structure. Although there is also a decrease in 5-HT levels no changes were observed in 5-HIAA levels as compared to controls. On the other hand, melatonin (2, 5, 10 and 25 mg/kg. i.p., daily for 7 days) treatment starting 1 h after 6-OHDA lesions, partially reverses the decreases caused by 6-OHDA lesions on these neurotransmitter levels, and contents were brought to approximately 50% of that observed in the contralateral sides of controls or of melatonin treated group. Melatonin was more efficient at the doses of 5 and 10 mg/kg, i.p., and effects were similar between the lowest and highest doses characteristic of a bell-shaped type of response. The apomorphine-induced rotational behavior (3 mg/kg, i.p.) was blocked by 60, 89, 78 and 47% after the doses of 2, 5, 10 and 25 mg/kg, i.p., respectively. Similarly, in this case the doses of 5 and 10 mg/kg were also more efficient. Melatonin (5 mg/kg) produced an upregulation of D1 receptors associated with a decrease in Kd value. While no change was observed in maximum density of D2 receptors, the Kd value was also decreased.

Astroglial and microglial reaction after a partial nigrostriatal degeneration induced by the striatal injection of different doses of 6-hydroxydopamine.

Astroglial and microglial activation was analyzed in adult male Wistar rats after a unilateral striatal injection of different doses (8, 4 and 1 micrograms) of 6-hydroxydopamine (6-OHDA). Control animals received the injection of the same volume of the solvent. The rotational behavior was registered by a rotometer 24 and 72 hours, 7, 10, 14 and 22 days after lesion. Following, animals were sacrificed and the tyrosine hydroxylase (TH) positive dopamine cells, the glial fibrillary acidic protein (GFAP) immunolabeled astrocytes and the OX42 immunoreactive microglia were visualized by mean of immunohistochemistry and quantified by stereologic method employing the optical disector and the point intercepts. The apomorphine (0.5 mg/kg)-induced circling behavior was seen only after 8 micrograms of 6-OHDA from 72 hours postlesion until sacrifice. Decreases of the TH immunoreactive terminals and cell bodies were found in the sampled fields of the striatum and pars compacta of the substantia nigra (SNc), respectively, after 8 and 4 micrograms of 6-OHDA. The GFAP immunohistochemistry revealed increases in the number/density of astroglial cells in the ipsilateral neostriatum (137% of control) and ipsilateral SNc (83% of control) and also in the volumeal fraction of the astroglial processes in the ipsilateral neostriatum (30% of control) and ipsilateral SNc (38% of control) in the rats with higher dose of the neurotoxin. Increases in the number of OX42 microglial labeled profiles and in the volumeal fraction of microglial processes were found in the ipsilateral neostriatum (67% and 27%, respectively, of control) and ipsilateral SNc (100% and 50%, respectively, of control) in the 8 micrograms 6-OHDA injected rats. These results suggest that the retrograde degeneration induced by a intrastriatal injection of a small dose of the 6-OHDA leads to an astroglial and microglial reaction in the nigrostriatal dopamine pathway. The interaction between activated glial cells may be involved in the wounding and repair events in the partial lesioned nigrostriatal system as well as in the paracrine responses to surviving dopamine neurons.

Anestésico para rinoseptoplastia / Anesthesia for rhinoseptoplasty

A 25 pacientes de uno y otro sexo y en buenas condiciones generales, se les hizo rinoseptoplastía bajo anestesia general balanceada e hipotensión controlada inducida con 2.4 mcg/kg de peso/minuto de nitroprusiato de sodio, previa administración de 1 mg/kg de peso de propanolol. La técnica permite un flujo sanguíneo periférico adecuado y no se hicieron aparentes signos de complicaciones neurológicas, cardiocirculatorias o metabólicas. Se describen los diferentes procedimientos anestésicos para el manejo de este grupo de pacientes y las consecuencias que conlleva la infiltración de catecolaminas exógenas y la liberación de sustancias vasoactivas endógenas