Disease relevance of lithium

• Analysis of normotensive offspring of hypertensives and of patients with secondary hypertension indicates that the temperature dependence of Li efflux may serve as a genetic marker for essential hypertension [1].
• Back pain and headache were the most common adverse events during LTG treatment; rash: LTG, 3%; Li, 6%; and PBO, 0; no serious rash was reported [2].
• In addition, malnutrition caused no discernible synergistic effects on Li/PC-induced status epilepticus [3].
• Weight gain (11 kg; 16.6% increase in 21 weeks) and improvement in manic symptoms occurred after QUET add-on to lithium (Li) [4].
• Men were more likely to have a seizure disorder and receive LI, CBZ, and PTN [5].

Psychiatry related information on lithium

• CONCLUSIONS: These results show that chronically administered Li+ and CBZ, but not VPA, increase the translocation of GRK3 from cytosol to membrane, possibly correcting supersensitivity of GPCRs in bipolar disorder [6].
• The patients had undergone identical FF challenge tests while drug free prior to commencing treatment with electroconvulsive therapy (ECT) (n = 4) or CMI supplemented with Li (n = 4) and after completing the above treatments [7].
• Lithium (Li) is an effective drug for prophylaxis and treatment of major affective disorders [8].
• Slow release preparations represent a means of maintaining stable Li plasma levels and thereby: [1] reducing side effects, [2] requiring fewer daily administrations, [3] possibly providing more stable therapeutic response and [4] improving patient compliance [9].

High impact information on lithium

• Mammary tumors induced in the presence of another mitogen, lithium (Li), do not have a mutation in the c-Ki-ras protooncogene [10].
• RESULTS: Chronic Li+ (24%) and CBZ (44%) significantly increased GRK3 in the membrane but not cytosol fractions [6].
• Both Li(+) and the GSK-3 inhibitor SB415286 induced neurite outgrowth of Neuro-2a cells [11].
• Interestingly, Axin, which is also a substrate for GSK-3, was destabilized by Li(+) and ectopic expression of Axin inhibited Li(+)-induced neurite outgrowth [11].
• Plasma prolactin (PRL) response to fenfluramine (FF) (60 mg orally) and placebo challenge was examined in eight remitted depressed patients who were withdrawn for 14 days from maintenance pharmacotherapy with clomipramine (CMI) plus lithium carbonate (Li) (n = 6) or Li alone (n = 2), 6 months after recovering from their major depressive episode [7].

Chemical compound and disease context of lithium

• Kinetic and thermodynamic properties of red cell lithium (Li) efflux were examined in patients with essential hypertension; the maximal rate of Li efflux as affected by temperature was measured at the range of 12 degrees to 42 degrees C. Fifty-two patients with essential hypertension and 22 normotensives were studied [1].

Biological context of lithium

• RESULTS: On Li(+) treatment, ectopic expression of the TCF/Lef-LacZ reporter gene was rapidly and dramatically induced in retinal explants [12].
• The pharmacokinetics of lithium (Li) uptake in rat head has been measured using STEAM localized spectroscopy for the whole brain, which showed relatively rapid uptake of Li and a steady level of Li from about 5 to 20 h [13].
• Under our conditions the uptake of Li increases with increasing hematocrit and blood age [14].

Anatomical context of lithium

• The GRK3 membrane to cytosol ratio was increased significantly in Li+ and CBZ treated rats [6].
• By contrast, the activity of the anion exchanger measured as the DIDS-sensitive lithium (Li) influx was similar in uremic versus control red blood cells (2.10 +/- 0.18 vs. 2.14 +/- 0.20 mmol/liter cells/hr) [15].
• In the first experiment, Li increased BDNF levels in rat hippocampus [16].

Associations of lithium with other chemical compounds

• More recent studies include regulatory pathways involving the phosphatidyl inositol/protein kinase C (PKC)-mediated pathway for regulation by lithium (Li) in low-K sheep red blood cells (LK SRBCs), and the nitric oxide (NO)/cGMP/protein kinase G (PKG) pathway as well as the platelet-derived growth factor (PDGF)-mediated mechanism in VSMCs [17].
• In the second experiment, AMPH decreased BDNF levels and Li and VPT increased BDNF levels in rat hippocampus [16].
• RESULTS: The plasma concentrations of the elements Li, Cs, Rb, and K distinctly decreased to 29, 50, 69, and 71%, respectively, of their initial values during hemodialysis [18].

Gene context of lithium

• Two-fold higher calbindin protein levels were found in Li-treated bipolar patients compared with other bipolar patients [19].
• OBJECTIVES: Therapeutically relevant concentrations of lithium (Li) exert an uncompetitive inhibition on inositol monophosphatase (IMPase) [19].
• PRL response to FF in the remitted, drug-free state was significantly enhanced compared to the response prior to treatment (while depressed and drug-free) and not significantly different from the response following treatment with ECT (n = 4) or CMI plus Li (n = 4) 6 months before [7].
• The rats subjected to lithium-pilocarpine (Li/PC)-induced status epilepticus at P21 were grouped as the SE group [3].
• These data suggest that pts with ICD have a plasma factor(s) which decreases net Na, Li and K reabsorption [20].

Analytical, diagnostic and therapeutic context of lithium

• The present study aims to investigate the effects of the mood stabilizers lithium (Li) and valproate (VPT) in an animal model of bipolar disorder [16].
• METHODS: During hemodialysis sessions, the concentrations of the five alkali metal cations lithium (Li), sodium (Na), potassium (K), rubidium (Rb), and cesium (Cs) have been determined in plasma and dialysis fluids of chronic hemodialysis patients by inductively coupled plasma mass spectrometry (Li, Rb, Cs) and by ion-sensitive electrodes (Na, K) [18].
• The products were characterized by elemental analysis, metal content determination and Fourier Transform Infrared (FTIR) Spectrum. Differential scanning calorimetry (DSC) profile indicated that Li and K salts of NTO and TABA undergo exothermic decomposition in the temperature range of 257-360 degrees C suggesting their energetic nature [21].
• Evidence supporting the use of lithium in the long-term care of bipolar disorder patients is unequaled; fluctuations of lithium (Li) plasma concentration, however, are associated with side effects at peak, and symptomatic states at trough, Li plasma levels [9].

References