Lithium (Li) represents a first choice mood stabilizer for bipolar disorder (BD). Despite extensive clinical use, questions regarding its mechanism of action and pathological mechanism of renal function impairment by Li remain open. The present study aimed to improve our knowledge in this area paying special attention to the relationship between the length of Li action, lipid peroxidation (LP), and Na+/K+-ATPase properties. The effects of therapeutic Li doses, administered daily to male Wistar rats for 1 (acute), 7 (short term) and 28 days (chronic), were studied. For this purpose, Na+/K+-ATPase activity measurements, [3H]ouabain binding and immunoblot analysis of α-Na+/K+-ATPase were performed. Li-induced LP was evaluated by determining the malondialdehyde concentration by HPLC. Sleep deprivation (SD) was used as an experimental approach to model the manic phase of BD. Results obtained from the kidney were compared to those obtained from erythrocytes and different brain regions in the same tested animals. Whereas treatment with therapeutic Li concentration did not bring any LP damage nor significant changes of Na+/K+-ATPase expression and [3H]ouabain binding in the kidney, it conferred strong protection against this type of damage in the forebrain cortex. Importantly, the observed changes in erythrocytes indicated changes in forebrain cortices. Thus, different resistance to SD-induced changes of LP and Na+/K+-ATPase was detected in the kidney, erythrocytes and the brain of Li-treated rats. Our study revealed the tissue-specific protective properties of Li against LP and Na+/K+-ATPase regulation.

• Klíčová slova
• Lithium, Malondialdehyde, Na+/K+-ATPase, Rat tissues, Sleep deprivation,
• MeSH
• antimanika aplikace a dávkování   farmakologie   MeSH
• bipolární porucha farmakoterapie   MeSH
• časové faktory MeSH
• erytrocyty účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   metabolismus   MeSH
• lithiumkarbonát aplikace a dávkování   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• sodíko-draslíková ATPasa metabolismus   MeSH
• spánková deprivace psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antimanika MeSH
• lithiumkarbonát MeSH
• sodíko-draslíková ATPasa MeSH

Lithium (Li) is a typical mood stabilizer and the first choice for treatment of bipolar disorder (BD). Despite an extensive clinical use of Li, its mechanisms of action remain widely different and debated. In this work, we studied the time-course of the therapeutic Li effects on ouabain-sensitive Na+/K+-ATPase in forebrain cortex and hippocampus of rats exposed to 3-day sleep deprivation (SD). We also monitored lipid peroxidation as malondialdehyde (MDA) production. In samples of plasma collected from all experimental groups of animals, Li concentrations were followed by ICP-MS. The acute (1 day), short-term (7 days) and chronic (28 days) treatment of rats with Li resulted in large decrease of Na+/K+-ATPase activity in both brain parts. At the same time, SD of control, Li-untreated rats increased Na+/K+-ATPase along with increased production of MDA. The SD-induced increase of Na+/K+-ATPase and MDA was attenuated in Li-treated rats. While SD results in a positive change of Na+/K+-ATPase, the inhibitory effect of Li treatment may be interpreted as a pharmacological mechanism causing a normalization of the stress-induced shift and return the Na+/K+-ATPase back to control level. We conclude that SD alone up-regulates Na+/K+-ATPase together with increased peroxidative damage of lipids. Chronic treatment of rats with Li before SD, protects the brain tissue against this type of damage and decreases Na+/K+-ATPase level back to control level.

• Klíčová slova
• Lipid peroxidation, Lithium, Na(+)/K(+)-ATPase, Rat brain, Sleep deprivation,
• MeSH
• antimanika farmakologie   terapeutické užití   MeSH
• hipokampus účinky léků   metabolismus   MeSH
• kompetitivní vazba účinky léků   MeSH
• krysa rodu Rattus MeSH
• lithiumkarbonát farmakologie   MeSH
• malondialdehyd metabolismus   MeSH
• ouabain metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• přední mozek účinky léků   enzymologie   metabolismus   MeSH
• sodíko-draslíková ATPasa metabolismus   MeSH
• spánková deprivace farmakoterapie   enzymologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antimanika MeSH
• lithiumkarbonát MeSH
• malondialdehyd MeSH
• ouabain MeSH
• sodíko-draslíková ATPasa MeSH

BACKGROUND: Lithium in the form of lithium carbonate (Li2CO3) has become one of the most effective and widely prescribed drugs for mood stabilization. However, lithium has adverse effects on renal tubular functions, such as decreased concentrating function of the kidneys, and even occasional symptoms of nephrogenous diabetes insipidus occur with additional evidence of glomerular disruption in lithium-treated patients. METHODS: We assessed the kidney function of patients with bipolar disorder who are under long-term lithium treatment using novel markers of kidney damage such as plasma neutrophil gelatinase-associated lipocalin, cystatin C, albuminuria, estimated glomerular filtration rate, Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, and serum and urinary osmolality, and compared the results with those of age-matched patients with bipolar disorder not treated with lithium. The study enrolled 120 patients with bipolar disorder, consisting of 80 (30 male and 50 female patients) who have been receiving lithium for 0.5 to 20 (mean, 7) years and 40 (10 male and 30 female patients) who had never been exposed to lithium treatment. RESULTS: Patients treated with lithium had significantly decreased urine osmolality (mean ± SD, 405 ± 164 vs 667 ± 174 mmol/kg) and urine-to-serum osmolality ratio (1.35 ± 0.61 vs 2.25 ± 0.96). No significant difference was found in creatinine, estimated glomerular filtration rate values calculated using the Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, neutrophil gelatinase-associated lipocalin, cystatin C, and albuminuria between both groups. We found no significant difference in renal biomarkers between patients treated with lithium for 6 to 24 months and those treated for 25 to 240 months. CONCLUSIONS: We found significantly decreased kidney concentrating ability in the long-term lithium-treated patients compared with the control group. Other renal function markers did not indicate any significant signs of renal dysfunction.

• MeSH
• antimanika aplikace a dávkování   škodlivé účinky   MeSH
• biologické markery metabolismus   MeSH
• bipolární porucha farmakoterapie   MeSH
• časové faktory MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace MeSH
• lidé středního věku MeSH
• lidé MeSH
• lithiumkarbonát aplikace a dávkování   škodlivé účinky   MeSH
• nemoci ledvin chemicky indukované   epidemiologie   MeSH
• senioři MeSH
• vyšetření funkce ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antimanika MeSH
• biologické markery MeSH
• lithiumkarbonát MeSH

Lithium is widely used in psychiatry to treat bipolar affective disorders since 1970 but little is known about the incidence, clinical course and associated factors of acute lithium intoxication. Moderate and severe cases of lithium intoxication are rare. This case reports a patient with acute lithium intoxication (serum level of 3.7 mmol/L) with neurological symptoms imitating stroke, which affects the differential diagnosis in the pre-hospital and hospital care. Patient was treated with forced diuresis and dismissed 21 days after admission.

• MeSH
• antimanika škodlivé účinky   terapeutické užití   MeSH
• bipolární porucha farmakoterapie   MeSH
• cévní mozková příhoda diagnóza   MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• lithium krev   MeSH
• lithiumkarbonát škodlivé účinky   terapeutické užití   MeSH
• předávkování léky krev   diagnóza   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antimanika MeSH
• lithium MeSH
• lithiumkarbonát MeSH

IMPORTANCE: Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). OBJECTIVES: To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. DESIGN, SETTING, AND PARTICIPANTS: A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. MAIN OUTCOMES AND MEASURES: Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. RESULTS: Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 × 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines. CONCLUSIONS AND RELEVANCE: This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.

• MeSH
• bipolární porucha farmakoterapie   genetika   MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• genetická zátěž MeSH
• genotyp MeSH
• HLA antigeny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lithiumkarbonát terapeutické užití   MeSH
• multifaktoriální dědičnost genetika   MeSH
• schizofrenie (psychologie) MeSH
• schizofrenie farmakoterapie   genetika   MeSH
• výsledek terapie MeSH
• zánět genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• HLA antigeny MeSH
• lithiumkarbonát MeSH

OBJECTIVE: Lithium has been long used in psychiatry as an adjuvant treatment for bipolar disorder. Chronic lithium intoxication is very rare. DESIGN: We present the case of a 72-year-old female, treated with lithium for more than 10 years for bipolar disorder, who was admitted for gait impairment with weakness of limbs, myoclonus, speech impairment and memory disturbances. RESULTS: Diagnosis of lithium intoxication was based on clinical picture and determination of serum lithium levels. EEG showed severe encephalopathy with triphasic wave complexes. Sensory and motor axonal neuropathy was observed by EMG. Discontinuation of the drug leads to clinical improvement, although not to a fully neurological recovery. CONCLUSION: Lithium is still very effective drug, but requires regular monitoring of serum levels to prevent overdose and symptoms of intoxication. Neurophysiological methods, including EEG and EMG, are strongly recommended to determine the level of peripheral and/or central nervous system impairment.

• MeSH
• antimanika škodlivé účinky   krev   terapeutické užití   MeSH
• bipolární porucha krev   farmakoterapie   patofyziologie   MeSH
• elektroencefalografie MeSH
• lidé MeSH
• lithiumkarbonát škodlivé účinky   krev   terapeutické užití   MeSH
• myoklonus krev   chemicky indukované   patofyziologie   MeSH
• nemoci mozku krev   chemicky indukované   patofyziologie   MeSH
• poruchy paměti krev   chemicky indukované   patofyziologie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antimanika MeSH
• lithiumkarbonát MeSH

• MeSH
• akutní poškození ledvin chemicky indukované   MeSH
• lidé MeSH
• lithiumkarbonát škodlivé účinky   MeSH
• mladiství MeSH
• nefrotický syndrom chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• Názvy látek
• lithiumkarbonát MeSH

Status epilepticus (SE) in developing rats leads to neuronal degeneration in many brain structures including neocortex but the functional consequences of cortical damage were studied only exceptionally. Lithium-pilocarpine SE was elicited in 12- (P12) and 25-day-old (P25) rats, convulsions were interrupted after 2h by paraldehyde. Cortical electrodes were implanted 3, 6, 9, 13 and/or 26 days after SE. Low-frequency stimulation of sensorimotor cortex was repeated with at least 10-min intervals with a stepwise increasing intensity (0.2-14 mA). Thresholds for movements elicited by stimulation, spike-and-wave afterdischarges (ADs), clonic seizures, mixed ADs (transition into a limbic type of ADs) and recurrent ADs as well as duration of ADs were evaluated. The first three phenomena were not influenced by SE with the exception of lower thresholds for movements during stimulation. Transition into limbic seizures and recurrent seizures were delayed in both age groups and threshold intensities for limbic ADs were at some intervals higher in SE than in control animals. Duration of ADs was changed only at short intervals after SE; it was shortened at 3 and 6 days in P25 and 3 days in P12 rats, respectively. P12 group then exhibited a transient increase in duration of ADs 6 days after SE. Our results did not prove a higher cortical excitability after SE in either age group. On the contrary, there were some signs of a decreased excitability.

• MeSH
• elektrická stimulace MeSH
• elektroencefalografie MeSH
• epilepsie tonicko-klonická patofyziologie   MeSH
• konvulziva MeSH
• krysa rodu Rattus MeSH
• lithiumkarbonát MeSH
• longitudinální studie MeSH
• mozková kůra patofyziologie   MeSH
• pilokarpin MeSH
• pohyb fyziologie   MeSH
• pohybová aktivita fyziologie   MeSH
• potkani Wistar MeSH
• stárnutí fyziologie   MeSH
• status epilepticus chemicky indukované   patofyziologie   psychologie   MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• konvulziva MeSH
• lithiumkarbonát MeSH
• pilokarpin MeSH

Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavícek et al., 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDŁ10; age 40+/-5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations.

• MeSH
• analýza rozptylu MeSH
• antidepresiva druhé generace aplikace a dávkování   terapeutické užití   MeSH
• antidepresiva tricyklická škodlivé účinky   terapeutické užití   MeSH
• antidepresiva škodlivé účinky   terapeutické užití   MeSH
• bipolární porucha farmakoterapie   MeSH
• citalopram škodlivé účinky   terapeutické užití   MeSH
• depresivní poruchy farmakoterapie   MeSH
• dospělí MeSH
• dothiepin škodlivé účinky   terapeutické užití   MeSH
• elektrokardiografie účinky léků   MeSH
• interpretace statistických dat MeSH
• kardiovaskulární fyziologické jevy účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lithiumkarbonát škodlivé účinky   krev   terapeutické užití   MeSH
• mapování potenciálů tělesného povrchu účinky léků   MeSH
• neparametrická statistika MeSH
• srdeční frekvence účinky léků   MeSH
• vektorkardiografie účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antidepresiva druhé generace MeSH
• antidepresiva tricyklická MeSH
• antidepresiva MeSH
• citalopram MeSH
• dothiepin MeSH
• lithiumkarbonát MeSH

Beginning with the seventies literature has brought a series of publications drawing attention to possible effects of lithium on the origin of congenital malformations. The discussion on the teratogenic effects of lithium in world literature has not come to final conclusion yet. The paper reviews some knowledge from home and foreign literature, dealing with the problems of lithium teratogenicity. A series of information has been provided on the basis of metaanalysis of data having been published until 1994 in the review systems MEDLINE, TOXLINE and Lithium Information Center database. The aim of the contribution has been to review the published data on this question. The available literature has shown that teratogenicity of lithium has not been proved univocally. Last studies rather suggest that lithium is not a strong teratogen. In view of the fact that teratogenicity of lithium cannot be safely excluded, the paper recommends that this kind of risk should be taken into account, if lithium administration is considered to be applied in pregnant women, especially during the first three months of pregnancy.

• MeSH
• abnormality vyvolané léky etiologie   MeSH
• antimanika škodlivé účinky   MeSH
• lidé MeSH
• lithium škodlivé účinky   MeSH
• lithiumkarbonát škodlivé účinky   MeSH
• těhotenství MeSH
• teratogeny * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antimanika MeSH
• lithium MeSH
• lithiumkarbonát MeSH
• teratogeny * MeSH