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Biomedical subjects

H Saavedra

Publications and source records attributed to H Saavedra.

At least 19 recordsLinked to original sources

Failure of one-day praziquantel treatment in patients with multiple neurocysticercosis lesions.

A recently described one-day regimen of praziquantel (PZQ) therapy for neurocysticercosis (NCC), three doses of 25 mg/k given at 2 h intervals, was applied in eight patients with viable NCC cysts without any evidence of inflammation. Resolution of lesions in computed tomography (CT) was observed in all five patients with a single cyst, whereas all cysts survived in three patients with multiple brain parasites. One-day praziquantel is a good regimen for patients with a single viable brain cysticercus but is poorly effective for multiple cysts.

Adult↗

Neuronal changes induced by chronic toluene exposure in the cat.

Chronic toluene inhalation provokes significant deleterious neurological effects in young glue sniffers and exposed workers. We have developed a chronic toluene inhalation model in the cat to address this issue. Neuronal changes using Loyez and acid fuchsinegallocianine stainings were studied at prefrontal cortex, cerebellun and hippocampus. All this structures showed varying degrees of neuronal degeneration to necrosis. Even if injury signs were widespread, the neuronal layers weren't equally affected and there were clear differences in injury severity. In the prefrontal cortex, injured neurons were observed in layers II, III and V/VI extending over several gyri. Lesions were time related, as was more clearly observed in Purkinje cells. In dorsal hippocampus alterations were particulary severe in CA1 and CA3. In ventral hippocampus damaged neurons were scarce and located mainly in CA2. The possible relation of this findings with behavioral changes observed during chronic toluene inhalation are noted.

Administration, Inhalation↗

Glutamate, GABA, calbindin-D28k and parvalbumin immunoreactivity in the pulvinar-lateralis posterior complex of the cat: relation to the projection to the Clare-Bishop area.

Neurons of the pulvinar-lateralis posterior complex (Pul-LP) containing glutamate (Glu) and GABA, as presumed neurotransmitters, and calbindin- D28k (calbindin) and parvalbumin (PV), as Ca-binding proteins, were identified in the cat by using immunohistochemical methods. In vibratome sections, neurons immunoreactive (IR) to each of the four antibodies were observed throughout the Pul-LP. In semithin sections, GABA-IR neurons were also PV-IR but not calbindin-IR and some of them also co-localized Glu. The Glu-IR neurons which were negative for GABA co-localized calbindin but not PV. The neurons of the Pul-LP projecting to the Clare-Bishop area (CB) in the suprasylvian gyrus were identified with a retrogradely transported tracer and the sections were then immunostained for Glu, GABA, calbindin and PV. Only Glu- and calbindin-IR neurons were retrogradely labeled. These results show that, if calbindin and PV have a Ca-binding role, the presumably excitatory Glu-IR neurons projecting to the CB are use calbindin whereas the presumably inhibitory GABA-IR neurons are intrinsic and use PV. This relationship implies that these proteins probably have other roles specifically related to the kind of agonist to be released at the neuron.

Animals↗

Successful treatment of Trypanosoma cruzi encephalitis in a patient with hemophilia and AIDS.

Although the frequency of infection with the human immunodeficiency virus (HIV) is increasing dramatically in areas where Trypanosoma cruzi is endemic, trypanosomiasis has been rarely reported in persons with HIV infection or AIDS. Persons with hemophilia who receive multiple blood product transfusions from blood banks with little or no screening for infectious agents are at particularly high risk for infections with both HIV and T. cruzi. We describe the case of a person with hemophilia who was infected by blood transfusion with HIV and T. cruzi and in whom a multifocal, necrotic trypanosomal encephalitis was demonstrated by brain biopsy and electron microscopy. Treatment with benznidazole followed by that with itraconazole and fluconazole was associated with significant clinical and radiographic improvement.

AIDS-Related Opportunistic Infections↗

Antinociceptive effects of Ca2+ channel blockers.

The antinociceptive action of four Ca2+ channel blockers, nifedipine, nimodipine, verapamil and diltiazem, was evaluated and compared to that of morphine using three algesiometric tests in mice and rats, namely, formalin, writhing and modified hot-plate test. Dose-response curves for all the drugs tested were similar and a significant dose-dependent antinociceptive action was evident in the formalin and writhing tests. However, in the hot-plate test, only nimodipine exhibited a significant analgesic effect, confirming the misleading results previously reported for this test. The findings suggest a pharmacological role of Ca2+ channel blockers in the modulation of antinociception under acute conditions. The analgesic action of Ca2+ channel blockers could be mediated by an increase in the nociceptive threshold resulting from interference with Ca2+ influx at opioid receptors, because Ca2+ influx is critical for the release of neurotransmitters and other substances implicated in nociception and inflammation. It is suggested that if a substance has a Ca2+ channel blocking effect, it should probably have some antinociceptive properties.

Analgesics↗

Cholinergic receptors in the human vas deferens.

This study represents the first investigation demonstrating the contractile response to exogenous acetylcholine (ACh) in the isolated human vas deferens. Pharmacological characterization of cholinergic receptors was achieved using selective antagonists to define receptor subtypes. In the HVD the effect of exogenous ACh is revealed as a dose-dependent sudden increase in the basal tension of the vasa. The ACh receptors of the HVD were competitively antagonized by atropine (ATR) with a high pA2 value (8.78). The main finding of this study is the presence of cholinergic receptors of the pharmacologically defined M1-ACh subtype in the isolated HVD, according to the pA2 values obtained with pirenzepine (PRZ) 7.39, AF-DX 116 (AF) 5.92 and 4-DAMP 5.65, M1-ACh, M2-ACh and M3-ACh selective antagonists, respectively. Prazosin (PZ), a selective alpha 1-adrenergic antagonist, displayed a similar competitive antagonism for the contractile response evoked both by ACh (pA2 = 8.69) and NE (pA2 = 8.58) in the HVD. The antagonism exerted by PZ on the ACh-induced contractile response of the HVD, suggests that ACh probably acts at a presynaptic level stimulating the release of NE from an adrenergic neuron. According to these findings, the receptor involved in this action, located in the proximity of the nerve terminals, seems to be of the M1-ACh subtype.

Acetylcholine↗

[Chagas disease with the acquired immunodeficiency syndrome. Clinical cases].

We report 2 patients with AIDS who developed Chagas infection, one with encephalitis, the other with acute myocarditis. The implications of immune depression for the manifestations and course of Chagas disease are discussed. Chagas disease should be considered in patients with AIDS who live in endemic zones and who develop cerebral or cardiac manifestations.

Acquired Immunodeficiency Syndrome↗

The effects of lesioning both the superior colliculus and the substantia nigra of cats on turning behavior.

In twenty two adult cats, distributed in four groups, stainless steel electrodes were implanted in the superior colliculus and the substantia nigra of both sides in order: 1) to find the current intensity threshold values necessary to evoke turning behavior, and record their variations after lesion of the cited structures; 2) to study the effects of lesioning two of these structures, specifically related to the direction of turning behavior, and 3) to assess the time-course of recovery from postural asymmetry after damaging two structures involved in rotation behavior, located either in the same or in the opposite side, as well as the importance of performing these lesions simultaneously or at different periods. Three main results were observed: 1) a large proportion of lesioned cats showed an increase in threshold values necessary to evoke rotation of the implanted structures located either in the same or in the opposite side; 2) the lesions induced in a significant number of cats a transient postural asymmetry. After lesioning the superior colliculus, the direction of turning was towards the damaged hemisphere. Apomorphine injected fourteen days later demonstrated the existence of an occult asymmetry, and the direction of turning was maintained. In the substantia nigra lesioned animals, the direction of turning, was towards the non-lesioned side. Apomorphine reversed the direction of turning; 3) the cats showed a remarkable capacity to recover from the postural asymmetry produced by the lesion. This experimental series further support the hypothesis of a close functional relationship between structures of both cerebral hemispheres related to turning behavior.

Animals↗

[A form for soliciting the measurement of drug plasma level and its use in a university hospital].

The correct clinical use of drug plasma levels is frequently jeopardized by neglecting to consider pharmacokinetic parameters at the time of sample drawing. A form to be filled at this time revealed that inadequate information concerning the drug was present in 28% and sampling time in 50% of cases. Accordingly, a new form is proposed to help avoid this information inadequacies and thus lead to better clinical use of drug plasma levels.

Aged↗

Analgesia produced by intrathecal administration of the kappa opioid agonist, U-50,488H, on formalin-evoked cutaneous pain in the rat.

The antinociceptive activity of the selective kappa opioid agonist U-50,488H, given intrathecally (i.t.) against chemically induced cutaneous pain in rats, was assessed from cumulative dose-response experiments and the formalin test. Three successive i.t. doses of 5, 10 and 35 nmol of U-50,488H produced a gradual reduction of pain scores which was statistically significant at all observation periods. This effect was antagonized significantly by 3 mg/kg i.p. of the opiate antagonists, naloxone and WIN 44,441-3. The analgesia profile showed a clear dose-response relationship. A dose producing 50% 'maximum possible analgesia' of 6.20 nmol (95% confidence interval: 3.05-12.59 nmol) was calculated. The results indicated that cutaneous pain of a chemical/inflammatory nature is highly sensitive to activation of kappa receptors of the spinal cord dorsal horn.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Eye movement-related neurons in the red nucleus.

Extracellular unit activity of the parvocellular red nucleus (RN) and spontaneous horizontal eye movements were recorded in adult, nitrous oxide-anesthetized and C1 transected cats. It was found that 7.5% of the neurons of each RN were related to spontaneous horizontal saccadic eye movements. Three types of neurons were observed: (1) bidirectional neurons which increased their frequency of discharge in relation to any horizontal eye movement; (2) unidirectional neurons which altered their frequency of discharge in relation to a horizontal eye movement of a precise direction; and (3) neurons which increased their frequency of discharge in relation to the rapid phase of an horizontal nystagmus. These 3 types of neurons modified their frequency of discharge before the initiation of the eye movement. One pair of oculomotor neurons recorded simultaneously in both RN showed a significant correlation coefficient. These results suggest that the RN may contribute to the preparation or execution of horizontal eye movements.

Animals↗

Evidence that the action of clonixin is non-dependent of ACh release.

1. The present study was designed to verify the ACh-mediated role in the action of ClX using cardiovascular and non-cardiovascular tissues taken from rats. 2. In the vasa deferentia preparations the muscular twitch induced by TNS was not changed by atropine, however in the presence of this drug, ClX induced a significant reduction of the height of the TNS-evoked twitch. 3. In the cardiorespiratory experiments, the administration of ClX produced a dose-dependent decrease in MAP, HR and RF. These effects were not changed by bilateral vagotomy and cervical sympathectomy. 4. The results obtained with atropine and with bilateral vagotomy and sympathectomy, attempt to delineate the possibility of a direct action of ClX. 5. All the evidence taken together does not support the hypothesis that ClX may be acting through an indirect action by releasing ACh.

Acetylcholine↗

[Antitubercular agents: pharmacogenetic factors in the development of adverse effects].

We studied the distribution of the acetylator phenotype in 47 patients aged 15 to 77 years receiving isonyazid as antituberculous therapy. 62% were fast and 32% slow acetylators. Ethnical, socio-economic and biologic factors were not related to acetylator type. The incidence of liver alterations, mainly elevated transaminase levels, was higher than reported in the literature and was not shown to be influenced by acetylator type. Adverse reactions to isonyacid were not related to drug serum levels.

Acetylation↗

Experimental cardio-depressant effects of clonixin.

1. The cardiovascular effects of CLX were studied. 2. CLX induced hypotension, bradycardia, negative chronotropism and negative inotropism. 3. Electrophysiological studies showed a decrease of sinus venosus discharge frequency. The action potential configuration was changed: the overshoot amplitude and (dV/dt)max were reduced and duration increased. 4. CLX at higher concentrations displaced the maximum diastolic potential and phase 4 slow diastolic depolarization was lengthened. 5. The above findings could be explained by a depressant action of CLX on the electrical activity of the pacemaker cells, possibly by a modification of the slow calcium currents.

Action Potentials↗

Evidence of a central component in the analgesic effect of indoprofene.

1. The central nervous system effects of the analgesic antiinflammatory drug, indoprofene were studied. 2. CNS effects were found using EEG in rats and cats. 3. Evoked cortical potentials were studied in cats, and evoked activity in ventroposterolateral thalamic nucleus and laminae V of spinal cord were studied in rats. 4. Indoprofene induced a modification of all the parameters studied. 5. Evoked activity of thalamic nuclei and laminae V were significantly depressed. 6. Central effects were not antagonized by naloxone. 7. It is postulated that indoprofene has a central component in its effect, which would contribute to its strong and rapid analgesic effect.

Analgesics↗

Further studies on the understanding of Octodon degus natural resistance to morphine: a comparative study with the Wistar rat.

1. Octodon degus shows higher levels of tolerance to morphine when compared with the Wistar rat. 2. In the formalin algesiometric test, this caviomorph is more resistant to pain (P less than 0.01) and to the analgesic effect of morphine (P less than 0.001). 3. CD50 and LD50 were significantly higher in Octodon degus as compared with Wistar rat. 4. Morphine caused in rat severe hypotension, while doses eight times higher in O. degus had a transient effect. 5. 3H-naloxone binding in adrenal glands of O. degus is higher than in other tissue samples assayed from the same animal or rats.

Adrenal Glands↗

New differences between the Wistar rat and Octodon degus, a putative laboratory animal resistant to morphine.

1. The effects of CNS depressants (methadone and alcohol) and natural neurotransmitters (NA and ACh) are studied in O. degus. 2. O. degus shows resistance to methadone in the formalin algesiometric test and EEG. 3. Ethanol elimination profile suggest the presence of an atypical alcohol dehydrogenase in O. degus 4. O. degus is extremely resistant to the pressor effects of noradrenaline 5. the isolated atrium of this rodent is 40 times more sensitive to the negative chronotropic effect of methadone, than the rat atrium. 6. These effects could be explained in terms of an important catecholamine and endorphin co-secretion from adrenal glands in O. degus.

Adrenal Glands↗

[Genetic polymorphism of isoniazid acetylation in Chilean patients with tuberculosis].

We studied genetic polymorphism of isoniazid acetylation in 47 tuberculous patients treated with 4 drugs between Aug 1987 and Dec 1988. Inactivation of isoniazid was estimated from urine samples after administration of the drug (10 mg/kg). There were 18 slow and 29 fast acetylators. The frequency of the slow mutant gene was estimated at 0.612, which is intermediate between values found in american natives (0.46) and western europeans (0.73). No associations of the presence of slow gene with sex, ABO group, ancestors, socioeconomic level, undernutrition, alcoholism or tobacco consumption were found.

Acetylation↗