Changes in the permeability of the blood-brain barrier in acute hyperammonemia

This study was designed to determine the contribution of elevated plasma ammonia levels to blood-brain barrier (BBB) abnormalities in the presence of intact liver. The permeability changes of the BBB were investigated grossly with Evans blue (EB) and quantitatively by measuring the blood-to-brain transfer content for α-aminoisobutyric acid (AIB) in normal rats and rats subjected to sublethal doses of ammonium acetate (NH₄OAc) (750 and 600 mg/kg ip; at 30-min intervals). Some rats were pretreated with dexamethasone (DXN). Injection of NH₄OAc increased both plasma and brain ammonia concentrations about 16- and 5-fold, respectively, above the control level. In rats receiving NH₄OAc injection, the blood-to-brain transfer constant (K _i) for AIB was increased 3-to 11-fold. The elevatedK _i values were limited to certain gray matter areas and less pronounced permeability changes were detected in white matter. Extravasation sites of EB were more restricted and were especially observed in thalamus and cerebellum, whereas cortex and white matter were unaffected. Dexamethasone pretreatment for 3d reduced both leakage of EB and theK _i for AIB in NH₄OAc injected animals, whereas acute treatment appeared ineffective. Dexamethasone did not prevent the development of coma but slightly decreased the ammonia concentration in plasma and brain. The results obtained indicate that hyperammonemia may disrupt BBB integrity not only to AIB and EB but also enhance the transport of other solutes.     

Antioxidant defence of the neonatal rat brain against acute hyperammonemia

Oxidative stress associated with the presence of elevated concentrations of ammonia in the brain has been proposed as one possible mechanism involved in ammonia toxicity. In a previous study [Brain Res.973 (2003) 31], we reported that neonatal rats are more resistant to acute ammonia toxicity than adult rats. In the present work, we studied the antioxidant status of the brain in hyperammonemic neonatal rats. Increased activities of the antioxidant enzymes and enhanced glutathione content were found in the brains of the hyperammonemic neonatal rats as compared to the controls. In addition, no changes in brain reactive oxygen species (ROS) levels and lipid peroxidation due to hyperammonemia were found. Therefore, acute ammonia intoxication does not induce oxidative stress in neonatal rats, a fact that may explain the resistance against hyperammonemia shown by neonatal rats.     

Tolerance of neonatal rat brain to acute hyperammonemia

The aim of the present work was to study the effects of hyperammonemia on brain energy metabolism in neonatal rats. Rats were rendered hyperammonemic by ammonium acetate administration. This decreased brain ATP concentrations but enhanced brain ammonia and lactate levels in both adult and neonatal rats. In adult rats, the decrease in brain ATP concentrations was accompanied by a plunge in the respiratory control rate (RCR) of brain mitochondria. However, the ammonia-induced effect on RCR was not observed in neonatal rats, suggesting that the fall in ATP levels observed in neonatal rats would not be due to an impairment of mitochondrial respiratory efficiency. However, in neonatal rats the increase in blood and brain ammonia concentrations did not change brain glutamate concentrations but decreased glutamine contents. These results may be of relevance for the understanding of the resistance of neonatal rats observed in this work to acute ammonia toxicity     

Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome

A 39-year-old man and his 42-year-old sister, both vegetarians, had episodic confusion for many years, but their mental function was normal between those episodes. They were recently diagnosed with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hyperammonemia was documented during an episode of confusion in the male sibling but not in his sister. Both had elevated plasma ornithine, glutamine, and alanine levels and persistently low plasma lysine levels. Homocitrulline was present in their urine, and orotic aciduria and orotidinuria developed in the male sibling following ingestion of allopurinol. Studies on their cultured skin fibroblasts showed deficient metabolism of ornithine, indicating a defect in ornithine transport across the mitochondrial membrane. During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal. Since therapy started, their clinical conditions have also improved, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months.     

Depot neuroleptics in the treatment of acute psychoses.

The data reported in the present study are derived from clinical records of 43 acute inpatients treated with the depot neuroleptic F.D. during a one year period, at the Psychiatric Institute of the University of Pisa. The criteria of selection of acute patients of schizophrenic, manic and schizoaffective type are reported. With such treatment it was possible to eliminate the stressful forced repeated drug administrations without any particular side-effects and the drug combinations were greatley reduced. However the clinical observations of this study need further confirm.     

Graded neurologic scale for use in acute hemispheric stroke treatment protocols

A standardized neurologic assessment scoring instrument was developed and tested for use in a multicenter trial of hypervolemic hemodilution in acute hemispheric stroke. Components of the neurologic examination pertinent to hemispheric stroke syndromes were emphasized. The scale was evaluated using 16 acute stroke patients for concurrent validity (Pearson coefficient r = 0.89 compared with global assessments by neurologists or neurosurgeons) and interobserver reliability (r = 0.95 interobserver reliability estimate). Such a scale should prove useful in quantifying neurologic deficits in hemispheric stroke and in following changes in neurologic status during multicenter acute treatment protocols.     

Bibliotherapy: the use of books in psychiatric treatment.

The guided use of selected books as an adjunct to treatment is applicable to patients in all stages of life and with a variety of problems. This paper describes the authors' experience using books as an adjunct to therapy with psychiatric patients. The authors define the term, review the literature, and set out the objectives of bibliotherapy. The paper presents some principles to follow when assigning books, and examples of books used for common problems. Finally, examples are given of bibliotherapy in action at two Ontario hospitals, and some future directions are suggested.     

The use of statins for the treatment of depression in patients with acute coronary syndrome

This study aimed to investigate the effect of statins for the treatment of depression in individuals with acute coronary syndrome (ACS). We used 1-year follow-up data of a 24-week double-blind, placebo-controlled trial of escitalopram and a naturalistic prospective observational cohort study. Of 446 participants with comorbid depressive disorders and ACS at baseline, 300 participated in a randomised escitalopram trial and the remaining 146 participated in a naturalistic observational study. The participants in the two studies were approached for a 1-year follow-up investigation. Treatment response rates, defined as a ⩾50% reduction in the Hamilton Depression Rating Scale (HAM-D) and Beck Depression Inventory (BDI) scores, were used as the outcome variables. In the escitalopram trial, both HAM-D and BDI response rates were highest in patients taking escitalopram and statins together and lowest in patients receiving neither medication. Logistic regression analyses revealed that statin use was significantly associated with higher response rates on both the HAM-D and BDI at 1 year, whereas no such associations were found for escitalopram. In the naturalistic observational study, the response rates at 1 year did not differ significantly by statin use. Instead, the HAM-D response rate was significantly higher in patients taking lipophilic statins than in those who did not. In conclusion, statins may be effective for the treatment of depression independent of medical status and escitalopram use, and they may potentiate the antidepressant action of serotonergic antidepressants in patients with ACS.     

New perspectives in the acute treatment of bipolar depression.

In contrast to mania, bipolar depression is usually characterised by longer-lasting episodes and a higher incidence of treatment refractoriness. Additionally, the risks of antidepressive standard treatment regimens are increasingly recognised, especially the risk of a switch into mania or induction of a rapid cycling course. Mood stabilisers, e.g. lithium, and some anticonvulsants, appear to have at least some antidepressant efficacy, which, however, may not be sufficient for treating severe depression. Currently, their use as a monotherapy of mild depression and at the start as a co-medication to antidepressants in severe depression is under consideration. The potential usefulness and risks of currently applied antidepressive treatment strategies as well as potential future developments will be reviewed in this article. At this stage, at least in severe depression, the use of true antidepressants still appears to be mandatory, especially because of the risk of suicide. However, initial combination with a mood stabiliser can be recommended. The treatment of depressive episodes only responsive to ECT should include combination with a mood stabiliser, in this case lithium, right from the start. In patients with lithium refractoriness, mood stabilising anticonvulsants should be initiated directly after the end of the ECT cycle. In order to reach sufficient plasma levels and thus reduce the risk of a switch, a loading therapy is recommended.     

Valproate-induced hyperammonemia as a cause of altered mental status.

The authors describe valproate-induced hyperammonemia and mental status changes in an 88-year-old man, the first known reported case in an elderly patient. They discuss this underrecognized complication of valproate use and the implications for treating elderly patients, in whom valproate use is increasing.     

Up-dating in acute ischemic stroke treatment.

Stroke is the second commonest cause of death world-wide, and the loss of quality-adjusted life years caused by stroke globally is bigger than for any other disease. The economic burden will be enormous if the nihilistic attitude that nothing can be done for stroke patients is not replaced by an active attitude. Clinical trials have shown that thrombolysis with rtPA is effective in acute ischemic stroke. A meta-analysis of these trials revealed that thrombolysis decreases the risk of death and dependency. All trials studying neuroprotecting agents have failed in man, although they have been successful in experimental animals. Protocolized intervention during the acute phase of ischemic stroke is proposed to correct physiological variables that have been disturbed in these patients. This intervention has been shown to have evident prognostic benefits. However, many of these measures are empirical and there is no clear evidence of their benefits. Organising the stroke units to be able to provide early thrombolysis for eligible patients will help all stroke patients in future treatments for ischemic stroke.

Neurología 2004;19(Supl 2):28-39

     

The use of steroids in the treatment of idiopathic polyneuritis.

The efficacy of steroids in the treatment of acute idiopathic polyneuritis (Guillain-Barré syndrome) continues to be uncertain. Since 1965, 38 patients with idiopathic polyneuritis have been at the University of Kentucky Medical Center, and 16 of them were entered in a prospective double blind study designed to assess the effectiveness of steroid therapy. Seriously ill patients were excluded from the study and most of them received steroids. In both the double-blind group and the entire group of patients, the time from the onset of illness to recovery was significantly less in patients treated with steroids, although steroids did not alter the initial severity of illness or the duration of hospitalization.