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Biomedical subjects

I Madrazo

Publications and source records attributed to I Madrazo.

At least 19 recordsLinked to original sources
PubMed2005

Glutathione monoethyl ester improves functional recovery, enhances neuron survival, and stabilizes spinal cord blood flow after spinal cord injury in rats.

Secondary damage after spinal cord (SC) injury remains without a clinically effective drug treatment. To explore the neuroprotective effects of cell-permeable reduced glutathione monoethyl ester (GSHE), rats subjected to SC contusion using the New York University impactor were randomly assigned to receive intraperitoneally GSHE (total dose of 12 mg/kg), methylprednisolone sodium succinate (total dose of 120 mg/kg), or saline solution as vehicle. Motor function, assessed using the Basso-Beattie-Bresnahan scale for 8 weeks, was significantly better in GSHE (11.2+/-0.6, mean+/-S.E.M., n=8, at 8 weeks) than methylprednisolone (9.3+/-0.6) and vehicle (9.4+/-0.7) groups. The number of neurons in the red nuclei labeled with FluoroRuby placed caudally to the injury site was significantly higher in GSHE (158+/-9.3 mean+/-S.E.M., n=4) compared with methylprednisolone (53+/-14.7) and vehicle (46+/-16.4) groups. Differences in the amount of spared SC tissue at the epicenter and neighboring areas were not significant among experimental groups. In a second series of experiments, using similar treatment groups (n=6), regional changes in microvascular SC blood flow were evaluated for 100 min by laser-Doppler flowmetry after clip compression injury. SC blood flow fell in vehicle-treated rats 20% below baseline and increased significantly with methylprednisolone approximately 12% above baseline; changes were not greater than 5% in rats given GSHE. In conclusion, GSHE given to rats early after moderate SC contusion/compression improves functional outcome and red nuclei neuron survival significantly better than methylprednisolone and vehicle, and stabilizes SC blood flow. These results support further investigation of reduced glutathione supplementation after acute SC injury for future clinical application.

Animals↗
PubMed2001

Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts.

BACKGROUND: Infection with the larval form of the pork tapeworm, Taenia solium, can lead to the development of cysts in the brain. Surgical removal of cysts has been the accepted treatment for neurocysticercosis characterized by giant cysts when there is associated intracranial hypertension. METHODS: We describe 33 patients whom we treated medically for malignant forms of neurocysticercosis. All patients had evidence of intracranial hypertension and subarachnoid cysts at least 50 mm in diameter. All patients received 15 mg of albendazole per kilogram of body weight per day for four weeks. Ten patients were also treated with 100 mg of praziquantel per kilogram per day for four weeks. Seventeen patients received a second course of albendazole, three received a third course, and one received a fourth course. During the first cycle of treatment, all patients also received dexamethasone. Five patients had previously undergone neurosurgery for giant cysts. RESULTS: After a median of 59 months of follow-up (range, 7 to 102), the condition of all 33 patients had improved, and the cysts had disappeared or become calcified. Of the 22 patients with a history of seizures, only 11 continued to receive antiseizure medications. The median quality-of-life score on the Karnofsky scale improved from 40 to 100. Fifteen patients received a ventriculoperitoneal shunt because of hydrocephalus. Four patients had persistent sequelae (bilateral partial optic atrophy, stroke, or diplopia) of the cysts. CONCLUSIONS: Intensive medical treatment can be effective in patients with neurocysticercosis characterized by giant cysts. Neurosurgery may be required only when there is an imminent risk of death.

Adolescent↗
PubMed2000

Lipid peroxidation inhibition in spinal cord injury: cyclosporin-A vs methylprednisolone.

To compare the effectiveness of cyclosporin-A (CsA) with methylprednisolone (MP) or a combination of both upon inhibition of lipid peroxidation (LP) after spinal cord (SC) injury, rats were treated with either CsA, MP, CSA+MP or vehicle starting 1 h after SC contusion at T9 level. LP was assessed 24h after injury by the lipid fluorescent product formation method. The survival rate was also evaluated in other series of rats by the Kaplan-Meier curves. Lipid peroxidation was similarly inhibited in rats treated with CsA, MP, or CSA+MP (p>0.05). Animals receiving MP (alone or combined with CsA) showed the poorest surviving rate. LP was inhibited by CsA to the same extent as by MP but without the lethal effect of the latter.

Animals↗
PubMed2000

Search for an IgG response against neural antigens in experimental spinal cord injury.

In order to determine if a specific response is induced after spinal cord injury, we performed a kinetic search for IgG antibodies against various spinal cord antigenic preparations in a rat contusion model. Even though spinal cord injured animals showed two reactive bands, these could be originated by the reaction of natural antibodies, since they were also observed before lesion. Thus, these antibodies would not be of relevance in the pathogenic events of spinal cord injury in this rat model. Our findings do not demonstrate the existence of a specific IgG response against spinal cord constituents after injury.

Animals↗
PubMed1998

Transitory expression of NADPH diaphorase (NOS) in axonal swellings after spinal cord injury.

To investigate the sites of nitric oxide synthase (NOS) expression after a spinal cord (SC) injury, NADPH-d diaphorase histochemistry was performed in the SC of adult rats sacrificed at different times from 1 h to 90 days after both SC contusion or transection. NOS could first be seen 12 h after injury in axonal swellings (AS) (club shaped structures at the tip of damage axons, associated with tissue destruction). NOS expression reached a maximum 3 days after injury, and gradually disappeared after 7 days. Finally, AS collapsed leaving behind microcysts. NOS expression and the consequent production of nitric oxide could be involved in the pathophysiology of the secondary damage, and/or could reflect a failed attempt for axonal regeneration.

Animals↗
PubMed1998

Spontaneous long-term remyelination after traumatic spinal cord injury in rats.

The capability of the central nervous system to remyelinate axons after a lesion has been well documented, even though it had been described as an abortive and incomplete process. At present there are no long-term morphometric studies to assess the spinal cord (S.C.) remyelinative capability. With the purpose to understand this phenomenon better, the S.C. of seven lesionless rats and the S.C. of 21 rats subjected to a severe weight-drop contusion injury were evaluated at 1, 2, 4, 6, and 12 months after injury. The axonal diameter and the myelination index (MI = axolemmal perimeter divided by myelinated fiber perimeter) were registered in the outer rim of the cord at T9 SC level using a transmission electron microscope and a digitizing computer system. The average myelinated fiber loss was 95.1%. One month after the SC, 64% of the surviving fibers were demyelinated while 12 months later, only 30% of the fibers had no myelin sheath. The MI in the control group was 0.72 +/- 0.07 (X +/- S.D.). In the experimental groups, the greatest demyelination was observed two months after the lesion (MI = 0.90 +/- 0.03), while the greatest myelination was observed 12 months after the injury (MI = 0.83 +/- 0.02). There was a statistical difference (p < 0.02) in MI between 2 and 12 months which means that remyelination had taken place. Remyelination was mainly achieved because of Schwann cells. The proportion of small fibers (diameter = 0.5 micron or less) considered as axon collaterals, increased from 18.45% at 1 month to 27.66% a year after the contusion. Results suggest that remyelination is not an abortive phenomenon but in fact a slow process occurring parallel to other tissue plastic phenomena, such as the emission of axon collaterals.

Animals↗
PubMed1997

Oral paracetamol bioavailability in rats subjected to experimental spinal cord injury.

The purpose of the present study was to examine the time dependence of oral paracetamol (acetaminophen) bioavailability in an experimental model of spinal cord injury (SCI). Female Sprague-Dawley rats were subjected to spinal cord contusion at the T8-T9 level by the weight drop method producing permanent paraplegia. Oral paracetamol bioavailability after administration of a single 100 mgkg-1 dose was determined 1, 12, and 50 d after SCI. Cmax and AUC were significantly decreased 1 d after SCI compared to sham-injured controls. This reduction, however, was temporary, as there was a recovery of bioavailability parameters which was partial 12 d after SCI, being complete by day 50. The present results confirm the usefulness of animal models for the characterization of the effect of SCI in drug kinetics. Data show that SCI induces significant changes in paracetamol pharmacokinetics. Nonetheless, despite the fact of a permanent loss of functions related to locomotion, pharmacokinetic alterations evolved with time.

Acetaminophen↗
PubMed1997

Albendazole and praziquantel treatment in neurocysticercosis of the fourth ventricle.

The purpose of this study was to determine the therapeutic efficacy of albendazole and praziquantel administration in the treatment of neurocysticercosis of the fourth ventricle. The authors report the results obtained in 10 patients with cystic neurocysticercosis of the fourth ventricle who were treated with albendazole at a dosage of 15 mg/kg/day for 2 weeks. Because of the failure of albendazole treatment, two of the patients received an additional course of praziquantel at a dosage of 100 mg/kg/day for 2 weeks. A total of 16 courses of albendazole and two courses of praziquantel were administered to the 10 patients. In eight patients (80%), there was complete disappearance of the cyst, in one other (10%) there was an important decrease in the size of the cyst, and in one (10%), no change was seen. None of the patients had complications during the follow-up period of between 6 and 26 months (average 15.7 months). The authors postulate that a regimen of albendazole is the treatment of choice for this type of neurocysticercosis, although praziquantel may also be useful.

Adult↗
PubMed1996

Histochemical evidence of the increased expression of nicotinamide adenine dinucleotide phosphate-dependent diaphorase in neurons of the myenteric plexus after acute spinal cord injury in adult rats.

The expression of nitric oxide synthase in neurons of the gastrointestinal tract (GIT) after experimental spinal cord injury (SCI) was assessed in adult rats contused at T8. One day and 10 weeks after injury, specimens along the GIT were studied for NADPH-diaphorase histochemistry. A significant increase in the number of positive cell bodies and fibers in the myenteric plexus were observed 1 day after SCI, as compared to specimens from control and chronically injured rats, with the exception of the colon, which showed unchanged or decreased number of positive neurons in the acute and chronic stages, respectively. Positive neurons in the submucous plexus remained unchanged, excepting an increase in the colon after acute SCI, and a decrease in the duodenum in chronically injured rats. The altered nitric oxide neurotransmission in the GIT may be relevant to its reduced motility after SCI.

Acute Disease↗
PubMed1996

Alteration of cyclosporin-A pharmacokinetics after experimental spinal cord injury.

The pharmacokinetics of the immunosuppressive agent cyclosporin-A (CsA) were studied in rats submitted to spinal cord (SC) injury. A single CsA 10 mg/kg dose was given either intraperitoneally (i.p.) or orally to rats submitted to experimental SC injury at the T8 level. Twenty four hours after lesion (acute stage of SC injury) i.p. CsA bioavailability was increased, while t1/2 was prolonged. However, oral bioavailability was reduced. Seven weeks after lesion (chronic stage of SC injury) CsA bioavailability, by either route, was not significantly different from control values. Results indicate that parenteral CsA bioavailability is increased during the acute stage of SC lesion, probably due to an impaired elimination. Oral bioavailability, however, is decreased, since there is also an important reduction in gastrointestinal CsA absorption that overrides the effect of impaired elimination. Alterations in CsA pharmacokinetics appear to revert during the chronic stage of SC injury. Changes in CsA bioavailability, depending on the route of administration and on time, must be considered to design an adequate immunosuppressive treatment in SC injury.

Administration, Oral↗
PubMed1996

Use of cyclosporin-A in experimental spinal cord injury: design of a dosing strategy to maintain therapeutic levels.

Cyclosporin-A (CsA) is frequently used as an immunosuppressive agent in experimental transplantations. CsA has been used in nervous tissue transplants in spinal cord injury (SCI). However, optimal results have not been obtained. This is likely due to the fact that SCI alters CsA pharmacokinetics and hence fixed dose regimens are not adequate. In this study, several CsA dosing regimens were evaluated in Long-Evans female rats subjected to a severe low thoracic (T8) SCI by the contusion method. Serum CsA concentrations were measured to determine which dosing regimen allowed CsA levels to be maintained within the therapeutic window. It was found that administration of 2.5 mg/kg/12 h intraperitoneally during the first 2 days after SCI (acute phase) followed by 5 mg/kg/12 h orally thereafter (subacute and chronic phases) yields CsA circulating levels within the therapeutic window, i.e., 0.120-0.275 microgram/mL. This dosing regimen represents a suitable alternative to fixed dosing to achieve an optimal CsA-induced immunosuppression in experimental models of SCI.

Animals↗
PubMed1996

Predictive value of signs and symptoms in the diagnosis of subarachnoid hemorrhage among stroke patients.

Clinical diagnosis of subarachnoid hemorrhage (SAH) is frequently misdiagnosed with intracerebral hemorrhage (ICH) or cerebral infarction (CI), which delays appropriate referral. This study was undertaken to create a clinical index to select, among stroke patients, those with the highest probability of having a SAH. Clinical data of patients with acute stroke were evaluated with the X2 and the Fisher exact test; a p value < 0.05 was considered significant. Significant variables were included in a "log-lineal regression analysis" where those with an odds ratio (OR) 95% confidence limits not including the unit were considered to construct an index using the odds ratio coefficient (C). The results indicated that of 197 records which were included, 22 cases of SAH and 175 of ICH or CI were demonstrated. Kappa coefficients for observer variation in clinical data retrieval was 0.91. After "log-lineal regression analysis" was carried out the following variables were significant: neck stiffness (C = 3, OR = 21); lack of focal neurologic signs (C = 2, OR = 6.88); and age < or = 60 years (C = 1.5, OR = 4.35). A fourth variable, seizures (C = 1, OR = 3.25), was marginally significant (p = 0.07), but added predictive value to the index. The positive predictive values of the sum of the coefficients were: 0 = 0%; 1-2 = 3%; 2.5-3.5 = 21%; 4-5 = 40%; 6.5 = 75%; 7.5 = 100%. In conclusion, when a stroke patient shows neck stiffness, or any combination of young age, lack of focal neurologic signs or seizures (a score > or = 2.5, the index has a 91% sensitivity and 82% specificity), he/she must be referred to a tertiary care center.

Adolescent↗
PubMed1996

Comparison between Sprague-Dawley and Wistar rats as an experimental model of pharmacokinetic alterations induced by spinal cord injury.

Two strains of rats, Sprague-Dawley and Wistar, were assayed in order to determine which strain is the more suitable experimental model for the study of pharmacokinetic alterations induced by spinal cord injury. Animals were submitted to spinal cord contusion at the T8-T9 level by the weight drop method. A single acetaminophen oral dose (100 mg/ kg) was administered 24 h after injury and blood samples were drawn for a period of 4 h. Acetaminophen concentration in whole blood was determined by high performance liquid chromatography and pharmacokinetic parameters were estimated. For both strains, Cmax and AUC were significantly lower, whereas tmax remained unchanged, in injured animals compared to sham-injured controls. Circulating acetaminophen concentrations were higher; therefore, pharmacokinetic alterations were more easily discerned, in Sprague-Dawley than in Wistar rats. It is concluded that the Sprague-Dawley strain is a more suitable model for the study of pharmacokinetic alterations induced by spinal cord injury.

Acetaminophen↗
PubMed1995

Fetal striatal homotransplantation for Huntington's disease: first two case reports.

Based on the successful use of fetal striatal brain grafting in the restoration of striatal function in rat and nonhuman primate models of Huntington's disease, as well as on the evidence for the clinical potential of fetal brain grafting in the treatment of Parkinson's disease, homotopic fetal striatal homotransplantations were performed in two huntingtonians. Case 1 was a 37 year-old female with moderate to severe Huntington's disease of 9 years evolution; case 2 was a 29 year-old male with mild Huntington's disease of 5 years evolution. Using open microsurgery, each patient was implanted to the ventricular wall of the right caudate nucleus with both striata from a 13 week-old and a 12 week-old human fetus, respectively. Since surgery both patients were kept on cyclosporine A. Surgery produced no damaging effect to either patient. The time course of the neurological progression of their disease, spanning 33 months for case 1, and 16 months for case 2, reveal that the disease in both patients has progressed more slowly in relation to their preoperative state. Although presently it is not possible to determine to what extent, surgery has modified the course of their disease, or if it will continue to have an effect on it, these surgeries represent the first step towards the development of brain grafting for Huntington's disease.

Adult↗