Therapeutic value of 21-aminosteroid U74389F in acute spinal cord injury

Abstract

The effect of bolus injections of 21-aminosteroid U74389F after an acute spinal cord compression trauma in rats was studied. Cortical somatosensory evoked potentials (CSEPs) were recorded before and after a weight-induced injury of 120 g and monitored up to five hours post-injury. All U74389F treatments were given as i.v. bolus injections of 15, 7.5, and 3.75 mg kg^–1 at 1, 2, 3 h after the trauma, respectively. The CSEPs were abolished immediately after the injury in the control and treated animals. The majority of the treated animals (88.8%) demonstrated a return of the CSEPs within the second hour post-injury. In contrast, the animals in the control group showed only 44.4% recovery at this time period. At three hours post-injury, U74389F-treated animals (n = 18) showed a full recovery (100%) while the recovery rate remained at 44.4% for the control animals. We conclude that the bolus administration of U74389F one hour after injury facilitates the return of the spinal cord function as measured by the CSEPs in this compression model of acute spinal cord trauma. [Neurol Res 1993; 15: 321-326]     

Neuropsychiatric symptoms in dementia: Importance and treatment considerations

Neuropsychiatric symptoms are frequent in people with dementia, result in distress for the people experiencing them and their caregivers, and are a common precipitant of institutional care. The safe and effective treatment of these symptoms is a key clinical priority, but is a long way from being achieved. Psychological interventions are recommended as the first line treatment strategy in most good practice guidelines, and there is emerging evidence of efficacy for agitation and depression. Neuroleptics remain the mainstay of pharmacological treatment, although meta-analyses indicate that they are mainly of benefit for the short-term (up to 12 weeks) treatment of aggression in people with Alzheimer's disease, and there have been increasing concerns about serious adverse effects including mortality. The evidence is limited for other pharmacological approaches for the treatment of agitation, and psychosis in people with Alzheimer's disease is limited, but post-hoc analyses do indicate that memantine may be a promising therapy and aromatherapy may be a useful alternative. Autopsy studies indicate that the adrenergic system may be an important therapeutic target. Clinical experience suggests that antidepressants are effective in people with severe depression in the context of dementia, but the evidence base regarding the broader value of antidepressants is far from clear. There are very few trials specifically focusing upon the treatment of neuropsychiatric symptoms in common non-Alzheimer dementias, which is a major limitation and urgently needs to be addressed to provide an evidence base to enable the safe and effective treatment of these individuals.     

Prevalence of mental health disorders among low-income African American adolescents

Purpose

Data on the prevalence of mental health disorders for low-income, urban African American adolescents are scarce. This study presents data about the burden of mental disorders for this understudied population.

Methods

Mental disorders were assessed using the Diagnostic Interview Schedule for Children (C-DISC), Youth Self-Report (YSR), and Child Behavior Checklist (CBCL) among a sample of adolescents and their caregivers from very impoverished neighborhoods in a Southern city.

Results

Based on the C-DISC, 3.8, 5.1 and 7.7 % of adolescents met diagnostic criteria for major depression, post-traumatic stress disorder, and conduct disorder, respectively. There were significant differences among some of the mental health disorders based on adolescent and caregiver characteristics such as sex, school status, caregiver work status, and income level. We found a low prevalence of alcohol, marijuana, and substance abuse and dependence disorders.

Conclusions

Information about the prevalence of mental health disorders in specific communities and populations can assist in addressing unmet needs, planning for services and treatment, and reducing health disparities.     

Neurotoxic effects of homocysteine on cerebellar Purkinje neurons in vitro

Whilst a plethora of studies that describe the toxicity of homocysteine to CNS neurons have been published, the effects of homocysteine on the Purkinje neurons of the cerebellum that play a vital role in motor function remain wholly unexplored. We have therefore established cultures of embryonic cerebellar Purkinje neurons and exposed them to a range of concentrations of homocysteine and determined its effects on their survival. The experiments revealed that all concentrations of homocysteine studied, from 50 to 500microM, caused a significant decrease in cerebellar Purkinje neuron number. This loss could be counteracted by the pan-caspase inhibitor z-VAD-fmk in the first 24h following homocysteine exposure, revealing that the initial loss was apoptotic. However, z-VAD-fmk could not prevent homocysteine-mediated loss of cerebellar Purkinje neurons in the longer term, after 6 days in vitro. In addition to its effects on Purkinje neuron survival, homocysteine markedly reduced both the overall magnitude and the complexity of the neurite arbor extended by the cerebellar Purkinje neurons, following 6 days incubation with this agent in vitro. Taken together our data reveal that homocysteine is toxic to cerebellar Purkinje neurons in vitro, inhibiting both their survival and the outgrowth of neurites.     

Factors Predicting Sodium Intake of Korean Americans with Type 2 Diabetes

The increasing prevalence of type 2 diabetes mellitus (T2DM) and its complications including cardiovascular disease and chronic kidney disease threaten Korean Americans (KAs). High dietary sodium intake contributes to both conditions. The purpose of the study was to assess dietary sodium consumption and to examine the predictors of sodium intake among KA with T2DM. A total 232 KA who had uncontrolled diabetes participated in this study. The majority of the sample (69%) consumed more sodium than current national guidelines. A high level of energy intake was the strongest predictor for sodium intake with gender and marital status also related. Our findings identified predictive factors to excessive sodium intake and these data support the need for culturally-tailored education about appropriate dietary sodium and energy intake are needed for patients about T2DM.     

Every-other-week methotrexate in patients with rheumatoid arthritis

Objective. To determine if patients with rheumatoid arthritis (RA) that is stable with weekly methotrexate (MTX) therapy could be switched to an every-other-week regimen of MTX. Methods. Forty-seven patients with classic or definite RA who had received MTX for at least 8 months were studied. Clinical measurements consisted of the number of tender and swollen joints, physician and patient global evaluation of disease activity on a 5-point scale, grip strength, patient evaluation of pain, morning stiffness, and the interval to onset of fatigue from time of awakening. Laboratory measures included the erythrocyte sedimentation rate (ESR), rheumatoid factor, C-reactive protein (CRP), and baseline serum folate levels. Uptake of MTX was measured with tritiated thymidine from peripheral blood mononuclear cells (PBMC) from patients ex vivo. Serum measures of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNFα) were performed in sera, and TNFα was also measured on PBMC supernatants. Results. Twelve of the 23 patients receiving every-other-week MTX (52%) were able to complete 6 months of this treatment without experiencing a disease flare. Eleven of the 23 patients receiving every-other-week MTX (48%) withdrew from the study before completing 6 months of treatment, because of a flare. No significant differences in clinical or laboratory parameters were seen when the 24 patients receiving weekly MTX were compared with the 12 patients in the every-other-week MTX group who successfully completed 6 months of the study. None of the changes in serum cytokine levels were significantly different between the patients receiving MTX weekly versus those receiving it every other week, and changes in ESR and CRP did not differ between groups. Age, sex, RA disease duration, MTX weekly dose or duration, baseline joint counts, or serum folate status did not predict a flare. Tritiated MTX uptake did not differ between groups. Conclusion. Some patients with RA that is stable on weekly dosing are able to change to every-other-week dosing without experiencing a flare in their disease activity.