Valproate metabolite concentrations in brain increase with chronic administration of sodium valproate

Rats were treated chronically with sodium valproate for varying periods of time up to eight weeks. A statistically significant negative correlation between plasma concentrations of valproate-derived substances (VDS) and length of treatment was observed while a statistically significant positive correlation was found between brain VDS concentration and length of treatment. Liver VDS concentrations showed a tendency to decrease with time but this trend was not statistically significant. A new procedure was developed to measure the tissue levels of VDS.     

Up-regulation of hippocampal glutamate transport during chronic treatment with sodium valproate

Excessive glutamatergic neurotransmission has been implicated in some neurodegenerative disorders. It would be of value to know whether glutamate transport, which terminates the glutamate signal, can be up-regulated pharmacologically. Here we show that chronic treatment of rats with the anti-epileptic drug sodium valproate (200 mg or 400 mg/kg bodyweight, twice per day for 90 days) leads to a dose-dependent increase in hippocampal glutamate uptake capacity as measured by uptake of [(3)H]glutamate into proteoliposomes. The level of glutamate transporters EAAT1 and EAAT2 in hippocampus also increased dose-dependently. No effect of sodium valproate on glutamate transport was seen in frontal or parietal cortices or in cerebellum. The hippocampal levels of glial fibrillary acidic protein and glutamine synthetase were unaffected by valproate treatment, whereas the levels of synapsin I and phosphate-activated glutaminase were reduced by valproate treatment, suggesting that the increase in glutamate transporters was not caused by astrocytosis or increased synaptogenesis. A direct effect of sodium valproate on the glutamate transporters could be excluded. The results show that hippocampal glutamate transport is an accessible target for pharmacological intervention and that sodium valproate may have a role in the treatment of excitotoxic states in the hippocampus.     

Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children

Antiepileptic drugs could cause changes in the trace element status of the body. Valproic acid (VPA) is a very effective anticonvulsant agent widely used in the management of various forms of epilepsy. Nail trace element content is a reliable index of trace element nutritional status of the body. To determine whether some of the side effects of antiepileptic drugs could be the result of zinc (Zn) depletion within tissues, Zn concentrations as well as copper (Cu) concentrations in nail and serum in 59 children having various types of epilepsy receiving valproate and 31 controls were assessed. Although serum Zn level in epileptic patients was found to be decreased, there was no difference in nail samples when compared to controls. There was a statistically significant increase in nail Cu level in epileptic patients when compared to controls. On the other hand, serum Cu levels were not different between the groups. Although none of our patients showed any symptoms of Cu elevation and Zn depletion, we should pay attention to potential body trace element changes in patients with epilepsy under VPA treatment. In conclusion, our results indicate that serum trace metal homeostasis might be affected by VPA therapy, but not by the convulsive disorder itself.     

Immunomodulators in combined therapy of patients with chronic hepatitis

The efficacy of the use of triple schemes in combined therapy of chronic virus hepatitis was estimated and its safety was monitored. The problems of therapy of mixed hepatitis in drug addicts are discussed. Immunotropic agents, increasing the efficacy of the standard therapy of chronic affections of the liver, are suggested to be used as the third remedy in the combined therapy.     

Erythropoietin therapy in patients with chronic renal failure.

Symptomatic anemia is a common complication of chronic renal failure. Treatment is now possible with the availability of recombinant human erythropoietin (epoetin alfa). Previous experimental studies have suggested that correcting the anemia of chronic renal failure may be harmful in that renal failure may be accelerated. Although experience with this drug has been primarily restricted to its use in patients with end-stage renal disease, several recent trials have been reported in patients with varying degrees of chronic renal failure. We review these studies with particular reference to the progression of renal failure and the drug''s reported side effects. We conclude that the use of epoetin is beneficial and well tolerated and that there is no compelling evidence for the acceleration of renal failure associated with its use in patients.     

Sleep quality in chronic kidney patients: a systematic review

The maintenance of sleep quality improves an individual’s quality of life and reduces the risk of death associated with disease, such as chronic kidney disease (CKD) (progressive and irreversible loss of kidney function). Poor sleep quality can negatively affect immunity, cognitive functions, and emotional manifestations. CKD patients have poor sleep quality in approximately 80% of cases. A systematic literature review was undertaken using online data bases. 73,734 studies were found, 21 of which met our inclusion criteria and were subject to detailed analysis. Although renal transplantation appears to be promising with regard to improving the quality of sleep of kidney patients, there is still a high prevalence of poor sleep even after the operation. Longitudinal studies are needed to understand better the risk factors that are involved and to indicate possible treatments that may improve the overall quality of life in this section of the population.     

Controlled trial of sodium valproate in severe epilepsy.

In a double-blind crossover trial sodium valproate or placebo was added to the existing anticonvulsant treatment of 20 patients with chronic uncontrolled epilepsy. Sodium valproate 1200 mg/day significantly reduced the frequency of both tonic-clonic and minor seizures in these patients. Only mild and transient side effects occurred (drowsiness, ataxia, and nausea), and these may have been due to the effect of adding sodium valproate to existing phenobarbitone or phenytoin treatment. Further controlled trials are needed to assess more fully the efficacy of this drug in various types of epilepsy.     

Effects of sodium valproate in 100 children with special reference to weight.

Excessive weight gain occurred in a patient who was taking sodium valproate and phenytoin. The sodium valproate was therefore withdrawn but the rapid weight loss that ensued led to phenytoin intoxication. Hence a retrospective analysis was conducted of 100 children with epilepsy treated with sodium valproate. Fit control improved in 77 and was best in children with generalised epilepsy. None of the reported severe side effects, such as acute liver disease and pancreatitis, were encountered. Milder but troublesome side effects, however, occurred in 65 patients. The commonest was increased weight gain, which occurred in 44 cases. Others were transient gastrointestinal disturbances (20), lassitude (nine), transient hair loss (six), transient enuresis (seven), and aggressive behaviour (four).     

Cardiac shockwave therapy in patients with chronic refractory angina pectoris

Background

Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT.

Methods

We included 33 patients (mean age 70?±?7 years, mean left ventricular ejection fraction 55?±?12?%) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3–7 spots/session, 100 impulses/spot, 0.09 mJ/mm²) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session.

Results

One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p?<?0.01) and the angina symptoms diminished from CCS class III to CCS class II (p?<?0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2?±?7.7?% to 56.4?±?9.4?%, p?=?0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4?±?2.8 to 8.8?±?3.6 min p?=?0.015). No clinically relevant side effects were observed.

Conclusion

CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

     

Improvement of herpetic stomatitis therapy in patients with chronic tonsillitis

To determine the clinicopathogenetic efficacy of cycloferon liniment in combined therapy of herpetic stomatitis, 60 patients with herpetic stomatitis and chronic tonsillitis were examined and treated. It was shown that the use of cycloferon liniment in the combined therapy of herpetic stomatitis in the patients with chronic tonsillitis allowed to lower the infection load in the parodontal recesses and the local inflammation, to normalize the immunity indices and to reduce the level of the endogenous intoxication, that provided acceleration of the recuperation processes and decreased the frequency of stomatitis backsets.     

Brain choline concentrations may not be altered in euthymic bipolar disorder patients chronically treated with either lithium or sodium valproate

BACKGROUND: It has been suggested that lithium increases choline concentrations, although previous human studies examining this possibility using 1H magnetic resonance spectroscopy (1H MRS) have had mixed results: some found increases while most found no differences. METHODS: The present study utilized 1H MRS, in a 3 T scanner to examine the effects of both lithium and sodium valproate upon choline concentrations in treated euthymic bipolar patients utilizing two different methodologies. In the first part of the study healthy controls (n = 18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking either lithium (n = 14) or sodium valproate (n = 11), and temporal lobe choline/creatine (Cho/Cr) ratios were determined. In the second part we examined a separate group of euthymic Bipolar Disorder Type I patients taking sodium valproate (n = 9) and compared these to controls (n = 11). Here we measured the absolute concentrations of choline in both temporal and frontal lobes. RESULTS: The results from the first part of the study showed that bipolar patients chronically treated with both lithium and sodium valproate had significantly reduced temporal lobe Cho/Cr ratios. In contrast, in the second part of the study, there were no effects of sodium valproate on either absolute choline concentrations or on Cho/Cr ratios in either temporal or frontal lobes. CONCLUSIONS: These findings suggest that measuring Cho/Cr ratios may not accurately reflect brain choline concentrations. In addition, the results do not support previous suggestions that either lithium or valproate increases choline concentrations in bipolar patients.