Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism.

BACKGROUND: Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms. OBJECTIVE: To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]). METHODS: Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI-MetS). RESULTS: Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI-MetS women as compared to NBMI ones. Spearman's correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes. CONCLUSION: Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.

Effects of 4-aminopyridine on attention and executive functions of patients with multiple sclerosis: Randomized, double-blind, placebo-controlled clinical trial. Preliminary report.

BACKGROUND: A high percentage of patients with multiple sclerosis present cognitive alterations. Because 4-aminopyridine improves nerve conduction and efficient synaptic connection could improve cognitive dysfunction. OBJECTIVE: To evaluate the efficacy on cognitive performance and safety of 4-aminopyridine administered to patients with relapsing-remitting multiple sclerosis. METHODS: A randomized, double-blind, placebo controlled clinical trial was conducted in patients with relapsing-remitting multiple sclerosis diagnosis according to the McDonald criteria. At the beginning and at the end of the treatment different tests were used to assess cognitive performance. Subsequently, patients were randomized 1:1 to receive treatment or placebo. A bootstrap-t test was proposed to test the effectiveness of cognitive performance, considering a p-value < 0.05 as statistically significant. RESULTS: Twenty-four patients were recruited of which 21 completed the trial, 11 with 4-aminopyridine and 10 with placebo treatment. No significant differences between groups in the initial assessments were observed. In terms of efficacy, the experimental group achieved significantly higher scores in attention span, verbal fluency, planning and graphics and constructive motion. CONCLUSIONS: 4-aminopyridine proved to be an effective treatment on cognitive aspects in patients with relapsing-remitting multiple sclerosis. Drug doses were shown to be safe with mild to moderate adverse events (ClinicalTrials.gov number, NCT02280096).

Adaptación y validación al español del cuestionario SMP-T2D para evaluar la autogestión de la hipertensión arterial más diabetes tipo 2: PAG-DT2+HTA / Adaptation and validation of the SMP-T2D questionnaire in Spanish for evaluating self-management of high blood pressure and type 2 diabetes: PAG-DT2+HTA

Antecedentes: Entre las condiciones crónicas a nivel mundial, la hipertensión arterial se presenta en uno de cada 3 adultos>40 años, mientras que uno de cada 10 adultos padece de diabetes de tipo 2. Para ambas enfermedades la adherencia al tratamiento farmacológico es>30% y la autogestión, que considera además la dieta y la actividad física, es desconocida porque ningún instrumento permite medirla. El objetivo del siguiente trabajo fue adaptar y validar el instrumento SMP-T2D en español, en pacientes con hipertensión arterial y diabetes de tipo 2. Métodos: Se hizo un proceso de adaptación del cuestionario SMP-T2D mediante la traducción al español, para ser utilizado en pacientes con hipertensión arterial más diabetes de tipo 2. Se realizó la validación convergente y discriminante. Se incluyó a pacientes mayores de 50 años con hipertensión arterial y a pacientes con hipertensión arterial más diabetes de tipo 2. Se eliminó a aquellas personas con cuestionario incompleto o sin consentimiento informado. Resultados: El PAG-DT2 + HTA fue aplicado a 145 pacientes; de ellos, el 54,4% tenían solo hipertensión y el 43,6% hipertensión arterial más diabetes de tipo 2. La edad promedio fue de 66,14 años (DE = 10,78), con una proporción de mujeres del 34,7% y de hombres del 65,3%. La consistencia interna por α de Cronbach del cuestionario fue 0,561 (p = 0,000). La correlación del PAG-DT2+HTA y Morisky-Green fue significativa (p < 0,05). Interesantemente, las personas con mayor educación y mayor remuneración económica alcanzaron una mejor gestión (validez de discriminación). Conclusión: El SMP-T2D que mide la autogestión en pacientes con diabetes de tipo 2, modificado y adaptado al español (PAG-DT2+HTA), también puede medirla en personas con diabetes de tipo 2 + hipertensión arterial

Background: High blood pressure is one of the most common chronic conditions worldwide. It affects one in every 3 adults over 40, while one in 10 suffers from diabetes. For both diseases, adherence to pharmacological treatment is over 30%, and self-management, which takes into account diet and physical activity, is still unknown, as there is no tool available to measure self-management. Therefore, the object of this study was to adapt and validate the Spanish version of the self-management profile for type 2 diabetes (SMP-T2D) questionnaire in patients with type 2 diabetes and high blood pressure among users of first level care in the social security institution of Mexico. Methods: The SMP-T2D was adapted to Spanish by translation into Spanish, and being used only in patients with high blood pressure and type 2 diabetes-hypertension. A convergent and discriminatory validation was performed. Patients over 50 years old with high blood pressure were include. Those that did not complete the questionnaire or give informed consent were rejected. Results: The Spanish version of the SMP-T2D was called PAG-DT2+HTA, and was applied to 145 people with hypertension: 54.4% with hypertension only, and 43.6% with hypertension and type 2 diabetes. Mean age was 66.14 years (SD = 10.78), with 34.7% women and 65.3% men. Internal consistency by α-Cronbach for the questionnaire was 0.561 (P = .000). The correlation between the PAG-DT2+HTA and Morisky-Green was significant. The ability to discriminate between people with and without education and with and without economic means was obtained. Conclusion: The Spanish version of SMP-T2D (PAG-DT2+HTA) that measures self-management in type 2 diabetes, can be used to measure self-management in people with type 2 diabetes-hypertension

[Adaptation and validation of the SMP-T2D questionnaire in Spanish for evaluating self-management of high blood pressure and type 2 diabetes: PAG-DT2+HTA]. / Adaptación y validación al español del cuestionario SMP-T2D para evaluar la autogestión de la hipertensión arterial más diabetes tipo 2: PAG-DT2+HTA.

BACKGROUND: High blood pressure is one of the most common chronic conditions worldwide. It affects one in every 3 adults over 40, while one in 10 suffers from diabetes. For both diseases, adherence to pharmacological treatment is over 30%, and self-management, which takes into account diet and physical activity, is still unknown, as there is no tool available to measure self-management. Therefore, the object of this study was to adapt and validate the Spanish version of the self-management profile for type 2 diabetes (SMP-T2D) questionnaire in patients with type 2 diabetes and high blood pressure among users of first level care in the social security institution of Mexico. METHODS: The SMP-T2D was adapted to Spanish by translation into Spanish, and being used only in patients with high blood pressure and type 2 diabetes-hypertension. A convergent and discriminatory validation was performed. Patients over 50 years old with high blood pressure were include. Those that did not complete the questionnaire or give informed consent were rejected. RESULTS: The Spanish version of the SMP-T2D was called PAG-DT2+HTA, and was applied to 145 people with hypertension: 54.4% with hypertension only, and 43.6% with hypertension and type 2 diabetes. Mean age was 66.14 years (SD=10.78), with 34.7% women and 65.3% men. Internal consistency by α-Cronbach for the questionnaire was 0.561 (P=.000). The correlation between the PAG-DT2+HTA and Morisky-Green was significant. The ability to discriminate between people with and without education and with and without economic means was obtained. CONCLUSION: The Spanish version of SMP-T2D (PAG-DT2+HTA) that measures self-management in type 2 diabetes, can be used to measure self-management in people with type 2 diabetes-hypertension.

Clinical and demographic profile of traumatic spinal cord injury: a Mexican hospital-based study.

STUDY DESIGN: Review of clinical data. OBJECTIVES: The objective of this study was to describe the clinical and demographical profile of patients with traumatic spinal cord injury (TSCI) admitted to a single center. SETTING: Unidad de Medicina Física y Rehabilitación Centro, México. PARTICIPANTS: Patients with TSCI attending rehabilitation for the first time. INTERVENTION: Not applicable. MAIN MEASUREMENTS: Age, gender, educational level, occupational activity, causes of injury, level of injury, neurological level, injury severity and category were recorded. RESULTS: Four hundred and sixty-four clinical files of patients with TSCI were collected. The mean age was 37.9 ± 15.9 years; 78.2% (363/464) were male, basic educational level predominated in 63.6% (296/464) and 73.1% (339/464) were employed. A fall was the main mechanism of the injury in 41.6% (193/464), replacing automobile accidents from the first place. The mean age of persons who suffered falls was 44 ± 16 years. Injuries sustained by younger persons were due to violence (28.4 ± 10.1 years) and the cause of injury associated with male gender was violence. Thoracic level was most often affected (in 56.7%, 263/464) and neurological level C4 in 13.4% (62/464). In regard to the extent of the injury, lesions classified as American Spinal Injury Association A predominated (56.2%, 261/464) as with complete paraplegia in 43.3% (201/464). CONCLUSIONS: The mean age of our patients was 37 years. Men are affected in a higher proportion. Our population has <9 years of study. Physical labor was the usual pre-injury activity. The main mechanism of injury was falls. Thoracic spine was the most affected.

Characterization of spinal subarachnoid bleeding associated to graded traumatic spinal cord injury in the rat.

STUDY DESIGN: Observational study in rats subjected to traumatic spinal cord injury (SCI). OBJECTIVES: To describe the features of spinal subarachnoid bleeding (SSB) occurring after graded SCI. SSB after SCI has been reported previously, but has not been studied systematically despite the fact that cerebral subarachnoid bleeding often produces severe neurological damage. SETTING: Mexico. METHODS: Anesthetized rats were subjected to mild or severe spinal cord contusion at T9. Occurrence, size, progression and location of SSB were characterized morphologically and scored from T7-T12 at 1 h and 1, 3 and 7 days post injury. Besides, contusions were videotaped to visualize bleeding at the moment of impact. RESULTS: SSB started immediately after contusion (severe or mild) and decreased gradually over time. For all vertebral segments, at all time points examined by histology, 48% of areas scored after severe contusion showed bleeding: 25% minor, 17% moderate and 6% major. After mild contusion, only 15% showed bleeding: 13 minor and 2% moderate. Maximum bleeding occurred early after injury in dorsal area of the epicenter in 100% of severe contusions (6% minor, 38 moderate and 56% major), and in 69% of mild contusions (63 minor and 6% moderate). CONCLUSION: Here, we detail SSB patterns occurring after graded SCI. Further studies are warranted to elucidate the possible role extramedullary events, such as SSB, in the pathophysiology of SCI that might encourage the development of new strategies for its management.

Autoreactivity against myelin basic protein in patients with chronic paraplegia.

INTRODUCTION: Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years. MATERIALS AND METHODS: Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetric-BrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed. RESULTS: SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 ± 1.5, mean ± SD) compared to control individuals (0.7 ± 0.3; P < 0.001). Humoral response analysis yielded a significant difference (P < 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses. CONCLUSION: This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages (>10 years) of injury.

Lack of neuroprotection with pharmacological pretreatment in a paradigm for anticipated spinal cord lesions.

BACKGROUND: In humans elective spine surgery can cause iatrogenic spinal cord injury (SCI). Efforts for neuroprotection have been directed to avoid mechanical injury by using intraoperative monitoring and improving surgical techniques. There is, however, uncertainty regarding the efficacy of neuroprotective drugs. STUDY DESIGN: Experimental study on the effectiveness of pharmacological neuroprotection in an animal model of spine surgery simulating anticipated mechanically induced neurological damage. OBJECTIVE: To compare the efficacy of four drugs to protect against the neurological effects of iatrogenic SCI. SETTING: Research Unit for Neurological Diseases, IMSS-Proyecto Camina, Mexico City, Mexico. METHODS: Erythropoietin, melatonin, cyclosporine-A and methylprednisolone were administered to rats before, during and after controlled spinal cord contusion of mild intensity. Dosage was in accordance with their pharmacokinetic properties and experience gained with experimental SCI. Drug efficacy was assessed by motor function recovery over a period of 6 weeks and by spinal cord morphometry. RESULTS: Compared with animals treated with saline, the drug-treated groups showed no differences in their locomotor performance, nor in the amount of spared cord tissue. Notably, spontaneous activity was significantly reduced in rats treated with cyclosporine-A. CONCLUSION: The neuroprotectant drugs used here perioperatively did not reduce the extent of neurological damage in a model simulating iatrogenic SCI. Therefore, for now, the only protection in elective spine surgery is avoidance of primary injury altogether.

Expression of neurotrimin in the normal and injured adult human spinal cord.

STUDY DESIGN: Neurotrimin (Ntm) is a member of the family of neural cell adhesion molecules. Its expression pattern suggests that Ntm promotes axonal fasciculation, guides nerve fibers to specific targets and stabilizes synapses as it accumulates coincident with synaptogenesis. Strong labeling of Ntm was observed in motor and sensory areas of the postnatal rat cortex. It is not known whether Ntm is present in adult human spinal cord (SC). In the present study, a monoclonal antibody specific for Ntm (1B1), is applied to the first study of the expression of Ntm in normal and injured adult human SC. OBJECTIVE: (1) To investigate the expression pattern of Ntm in adult normal human SC, and (2) to observe the changes of Ntm expression after SC injury and compare the differences between normal and injured adult human SC. METHODS: Human SC tissue was obtained from necropsies of patients with (n=5) and without (n=4) SC injury. The 1B1 Ntm monoclonal antibody was used for immunohistochemical staining on paraffin embedded sections with an ABC kit. RESULTS: (1) In total, 12 slides were analyzed for each group from both cervical and thoracic levels. Motor neurons and Clarke's neurons and glial-like cells were mild to moderately positive in all uninjured SC specimens. (2) In injured SC, no staining was observed in the injury epicenter between two and three levels proximally and distally, but was detected five levels away. (3) In patients older than 67 years of age, Ntm-positive inclusions were present in the white matter of the SC with or without injury. (4) Some meningeal cells were strongly Ntm-positive, especially in the uninjured human SC. CONCLUSION: Ntm is expressed by motor and Clarke's neurons and glial cells in uninjured human SC. The downregulation of Ntm in the injured SC suggests that its expression is regulated by afferent input.

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.

[Carotid-basilar artery communication in gerbils (Meriones unguiculatus)]. / Comunicación arterial carotidobasilar en gerbos (Meriones unguiculatus).

INTRODUCTION: Since 1966 when Levine and Payan observed that the Mongolian gerbil (Meriones unguiculatus) was unusually susceptible to cerebral infarction following occlusion of one or both common carotid arteries, the model has been used for the experimental study of cerebral ischemia. OBJECTIVE: To assess the presence of anterior-posterior arterial communication in the Mongolian gerbil (Meriones unguiculatus). MATERIAL AND METHODS: 26 animals were used and divided in the following groups: 1. Bilateral carotid ligation (n = 10); 2. Unilateral left carotid ligation (n = 5); 3. Unilateral carotid right carotid ligation (n = 5); and 4. Control group without carotid ligation (n = 6). RESULTS: Postmortem intra-aortic dye injection demonstrated communication between anterior and posterior cerebral arteries in 30% of gerbils that previously were subjected to bilateral common carotid artery occlusion. A number of vessels, between 8.95-11.35 microns in diameter, were linking the basilar artery with the posterior cerebral artery. In the remaining animals, the absence of communication was confirmed. CONCLUSION: Communicating carotid-basilar in lower number of cases and anastomosis the smallest diameter to give the gerbil advantage on others species as model of experimental regional ischemia.

Comunicación arterial carotidobasilar en gerbos (Meriones unguiculatus) / Carotid-basilar arterial communication in gerbils (Meriones unguiculatus)

Introducción. El modelo en gerbos para la investigación de la isquemia cerebral por oclusión bilateral y unilateral de la arteria carótida común ha sido empleado desde 1966, cuando Levine y Payan lo describieron como susceptible de desarrollar infarto cerebral y signos de daño neurológico por variantes de la circulación anastomótica cerebral. Objetivo. Demostrar la presencia de comunicaciones arteriales entre la circulación cerebral anterior y posterior. Material y métodos. La muestra la forman 26 gerbos que fueron anestesiados para exponer y ocluir las arterias carótidas comunes: 1. Grupo bilateral (n= 10); 2. Carótida izquierda (n= 5); 3. Carótida derecha (n= 5); 4. Sin oclusión (n= 6). Posteriormente se sacrificaron para perfusión intraórtica, inicialmente con solución salina (0,9 por ciento) y paraformaldehído (4 por ciento), y finalmente con colorantes para teñir las arterias. Los cerebros fueron extraídos 24 horas después y posfijados una semana más, para estudiar la circulación arterial cerebral, su distribución y la medición de diámetros de los vasos principales y secundarios, especialmente de los vasos terminales del tronco vertebrobasilar y de la arteria cerebral posterior. Resultados. Se encontró, en 30 por ciento de los animales con oclusión bilateral, pequeños vasos comunicantes posteriores de diámetro variable, entre 8,95 y 11,35 µm. En los restantes animales examinados no se encontró comunicación entre el sistema vertebrobasilar y el sistema carotídeo. Conclusión. La comunicación carotidobasilar, en menor número de casos y con anastomosis de diámetro pequeño, le dan al gerbo ventaja sobre otras especies como modelo de isquemia regional (AU)

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.

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.

Cyclosporin-A inhibits lipid peroxidation after spinal cord injury in rats.

Besides its immunosuppressive/anti-inflammatory activity, cyclosporin-A (CsA) may protect damaged tissues from lipid peroxidation (LP) by free radicals. To determine the effect of CsA on LP spinal cord (SC) injury, Wistar rats were treated with either vehicle or CsA (2.5 mg/kg per 12 h i.p.) 1, 2, 6 or 12 h after SC trauma by T8-T9 spinal cord contusion, analyzing LP 24 h after injury at the lesion site by the lipid fluorescent products formation method. CsA significantly diminished LP to levels below control values after contusion (P < 0.05). The greater inhibition was observed when CsA was given during the first 6 h after injury, furthermore, animals showed a significant clinical improvement. Results show that CsA may be beneficial to injured tissue by inhibiting the levels of LP.

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.

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.

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.